DISCUSSION Open Access Evaluation of evidence that the … · 2018-03-02 · DISCUSSION Open Access...

Giesy et al. Environmental Sciences Europe 2014, 26:29http://www.enveurope.com/content/26/1/29

DISCUSSION Open Access

Evaluation of evidence that the organophosphorusinsecticide chlorpyrifos is a potential persistentorganic pollutant (POP) or persistent,bioaccumulative, and toxic (PBT)John P Giesy1, Keith R Solomon2*, Don Mackay3 and Julie Anderson4

Abstract

A number of chemicals, including several organochlorine pesticides, have been identified as persistent organicpollutants (POPs). Here, the properties of chlorpyrifos (CPY; CAS No. 2921-88-2) and its active metabolite,chlorpyrifos oxon (CPYO; CAS No. 5598-15-2), are assessed relative to criteria for classification of compounds aspersistent, bioaccumulative, and toxic substances (PBTs). The manufacture and use of POPs are regulated at the globallevel by the Stockholm Convention (SC) and the UN-ECE POP Protocol. Properties that result in a chemical beingclassified as a POP, along with long-range transport (LRT), while understood in a generic way, often vary amongjurisdictions. Under the SC, POPs are identified by a combination of bulk (intensive) properties, including persistenceand biomagnification, and an extensive property, hazard. While it is known that CPY is inherently hazardous, what isimportant is the aggregate potential for exposure in various environmental matrices. Instead of classifying chemicals asPBT based solely on a few simple, numeric criteria, it is suggested that an overall weight of evidence (WoE) approach,which can also consider the unique properties of the substance, be applied. While CPY and its transformation productsare not currently being evaluated as POPs under the SC, CPY is widely used globally and some have suggested that itsproperties should be evaluated in the context of the SC, especially in locations remote from application. In Europe, allpesticides are being evaluated for properties that contribute to persistence, bioaccumulation, and toxicity under the aegisof EC Regulation No. 1107/2009: ‘Concerning the Placing of Plant Protection Products on the Market.’ The properties thatcontribute to the P, LRT, B, and T of CPY were reviewed, and a WoE approach that included an evaluation of the strengthof the evidence and the relevance of the data to the classification of CPY and CPYO as POPs or PBTs was applied. Whiletoxic under the simple classification system used in EC Regulation No. 1107/2009, based on its intensive properties andresults of monitoring and simulation modeling, it was concluded that there is no justification for classifying CPY or itsmetabolite, CPYO, as a POP or PBT.

Keywords: Stockholm Convention; EC Regulation No. 1107/2009; Chlorpyrifos oxon; Long-range transport

BackgroundA number of chemicals, including several organochlorinepesticides, have been identified as persistent organicpollutants (POPs). The POPs were first brought to theattention of the general public by Rachel Carson in herbook Silent Spring [1]. In that now famous book, shepointed out that a number of chemicals, including the

* Correspondence: [email protected] for Toxicology, School of Environmental Sciences, University ofGuelph, Guelph, ON N1G 2 W1, CanadaFull list of author information is available at the end of the article

© 2014 Giesy et al.; licensee Springer. This is anAttribution License (http://creativecommons.orin any medium, provided the original work is p

pesticide dichlorodiphenyltrichloroethane (DDT) and itstransformation products, dichlorodiphenyldichloroethylene(DDE) and dichlorodiphenyldichloroethane (DDD), werenot only persistent but also biomagnified in food chains,caused adverse effects in non-target organisms, such asbirds, and underwent long-range transport (LRT) to moreremote and pristine areas, such as the Arctic and Antarctic.At about the same time, it was recognized that a number ofother organochlorine pesticides and the industrial chemicalpolychlorinated biphenyls (PCBs) also had properties con-sistent with them being POPs. Since that time, these and

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additional chemicals have been identified as POPs and themanufacture and use of these substances are regulated at theglobal level by the Stockholm Convention (SC) [2] and theUN-ECE POP Protocol [3]. While many of the chemicalsclassified as POPs have been organochlorines, some such asthose that contain the terminal degradation product, per-fluorooctanesulfonate (PFOS) are not. As in many regulatorysystems, the SC uses the precautionary approach; however,this includes detailed scientific review by the POPs ReviewCommittee, where there is an opportunity to consider theinherent properties of the chemical under review.While understood in a generic way, the properties that

are used to derive criteria for classification of a chemicalas a POP with LRT, or a PBT, are used differently amongjurisdictions [4,5]. Under the global aegis of the SC, POPsare identified by a combination of intensive properties(independent of concentration), including persistence,biomagnification, and chemical and physical propertiesthat result in harmful interactions with biological systems,and extensive properties (dependent on concentration),including toxicity, hazard, and risk. In addition to the SC[2], several additional frameworks have been developed toassess chemicals based on the properties of persistence,bioaccumulation, and toxicity (P, B, and T). Some of theseframeworks are international, such as the Conventionfor the Protection of the Marine Environment of theNorth-East Atlantic [6]. Others are regional, such as theEU legislation Registration, Evaluation, Authorisation andRestriction of Chemicals (REACH [7]), with a focus on che-micals in commerce, and EC Regulation No. 1107/2009 [8],which is focused on pesticides. National frameworksinclude, for example, the Toxic Substances ManagementPolicy [9], the Toxics Release Inventory Reporting [10], andthe Chemicals Management Plan in Canada [11].Classifying chemicals as POPs or having the properties

of PBTs is used to assist industries in making decisionsabout the development of chemicals and governments inpriority setting and regulation of these chemicals. Theconcepts of persistence, bioaccumulation, and toxicityare commonly used in the scientific literature, as is theinternationally used concept of a POP. PBT, as a term,appears to have originated in policies of the Japanesegovernment in the 1970s, even though the term did notappear in the peer-reviewed scientific literature until the1990s [5]. This term and underlying concepts are beingused increasingly by policy makers in regulatory deci-sions. Unfortunately, inconsistent definitions and criteriafor classifying chemicals as being PBT vary among juris-dictions and have been changing over time. Further-more, this very simplistic method of classification doesnot take into account the unique properties of chemicalsor the environments to which they are released [12].These shortcomings are exacerbated by both poorquality of data and, in some cases, little or a complete

lack of data, such as was the case for perfluoroundecanoicacid [5].There are a number of uncertainties in these approaches

that require interpretation of metrics such as persistence invarious media, bioaccumulation, and toxicity. Since every-thing can be toxic, the critical issue is not the inherenttoxicological properties of a chemical, which is its potency,but the concentration to which it can accumulate intovarious matrices of the environment. Ultimately, interpret-ation of the potential for harm that can be caused by achemical of concern (COC) is duration and intensity ofexposure that determines the severity and rate of damage.Injury occurs when the rate of damage exceeds the rate ofelimination and/or repair. So the concept of toxicity needsto be considered not in abstract or absolute terms, butrelative to exposures. Of the three principal parametersused to classify chemicals, toxicity is the least welldescribed and interpretable. Adverse effects are onlyobservable when the concentration (exposure) of a sub-stance exceeds the threshold for effects for a sufficient dur-ation. Because of its intensive properties, a chemical, suchas the organophosphorus pesticide chlorpyrifos (CPY), canhave relatively great potency to cause adverse effects, but ifthe concentrations in various matrices do not exceedthresholds for adverse effects, there is no adverse effect.Risk is defined as the likelihood for exceedence of a thresh-old (used here in the inclusive sense) and is alwaysexpressed as a probability. This has been known for sometime, as attributed to Antoine Arnauld in a monastic textin 1662: ‘If, therefore, the fear of an evil ought to be pro-portionate, not only to its magnitude, but also to its prob-ability…’ (page 368 in [13]). Several properties drive theprobability of exposure but the most important parameteris persistence. If a COC is sufficiently persistent, then thereis always the potential for accumulation and toxicity. Evenif a compound degrades relatively rapidly, if it is releasedcontinuously or organisms are exposed for a sufficient dur-ation, it might be present in sufficient quantities to exerttoxicity. Such substances have been termed ‘pseudo persist-ent.’ So here the classification of CPY as a POP is consid-ered not only relative to specific, absolute ‘trigger’ valuesfor the classifying parameters but also relative to what islikely to occur in the environment. That is, while it isknown that CPY is inherently hazardous, what is the aggre-gate potential for exposure in various environmentalmatrices [14,15]? Instead of classifying chemicals asPBT based solely on a few simple, numeric criteria, atransparent weight of evidence (WoE [16]) approach,which can also consider the unique properties ofCOCs, should be applied [5,17]. This approach allowsall relevant scientific data to be considered on a case-by-case basis, but the process of classification requiresmore description of the process and expert evaluationof the results of the multiple lines of evidence.


While CPY and its transformation products are not cur-rently being formally evaluated as POPs under the SC, ithas undergone simplified screening as an alternative toendosulfan. This screening suggested that CPY mightmeet all Annex D criteria (be a POP) but there are onlyequivocal or insufficient data [18]. CPY is widely usedglobally and some have suggested that its propertiesshould be evaluated in the context of POPs [19]. InEurope, all pesticides (excluding biocides used to controlbacteria and fungi) are being evaluated for properties thatcontribute to persistence, bioaccumulation, and toxicity(PBT) under the aegis of EC Regulation No. 1107/2009:‘Concerning the Placing of Plant Protection Products onthe Market’ [8]. Under EC Regulation No. 1107/2009,products identified as POPs under the SC are not allowedto be used.Properties that contribute to P, LRT, B, and T of CPY

have recently been reviewed [15,20]. These reports werepart of a series devoted to assessing risks to environmentsassociated with the use of CPY in the United States ofAmerica (USA). This report builds on these previousreports but refines the assessment with a WoE approachthat includes an evaluation of the strength of evidence andrelevance of the data to classification of CPY as a POP orPBT. There is general recognition that industry has aresponsibility to evaluate its commercial products, espe-cially chemicals such as pesticides, for their possible envir-onmental impacts. One approach for doing this is to usePOP and PBT criteria as a basis for quantitative evaluationof properties, even when there is little likelihood that thechemical will be considered or declared to meet thesecriteria. In short, established POPs and PBTs are used as‘benchmarks’ against which the chemical in question can becompared. It is partly in this spirit that this evaluation wasundertaken.Chemicals can be assessed and classified as PBTs under

several auspices with varying sets of guidelines. Whilethere is some guidance on how the classification shouldbe done [21], none of these processes are inherentlyassessments of risk. That is, they do not consider

Table 1 Criteria for categorization of compounds as POPs and

Persistent (P) Bioaccumulative (B) Toxic (T)

Water: DT501

> 2 monthsBCF or BAF >5,000 or Log KOW >5 No specific

adverse humenvironmen

Sediment:DT50 >6 months

High bioaccumulation in other species, hightoxicity or ecotoxicity

Soil: DT50 >6 months

Otherevidence ofpersistence

Monitoring data in biota indicating that thebioaccumulation potential is sufficient to justifyits consideration within the SC

From [2,3], 1DT50; note that the SC uses the term half-life but does not state whethe

probabilities of exceeding threshold concentrations for de-fined effects in the environment. At best, these processesare an evaluation of measured or predicted parametersthat relate to persistence in various media and the poten-tial to bioconcentrate or biomagnify.Since there were no predefined criteria for identification

of POPs, they have been developed over time by various in-dividuals and/organizations from empirical observations ofa number of chemicals that were observed to be persistent,biomagnified, and transported over long distances. Thus,the chemical, physical, biological, and environmental prop-erties of the so-called ‘dirty dozen’ [22,23] were used as thebasis for the trigger values for persistence (P), bioaccumula-tion (B), toxicity (T), and propensity for long-range trans-port (LRT) that are currently used under the SC (Table 1).As has been pointed out elsewhere [17,24], there are noconsistently applied criteria for classification of B other thanthe bioconcentration factor (BCF) in EC Regulation No.1107/2009. Although the bioaccumulation factor (BAF) isalso used in the SC, other criteria for B, such as thebiomagnification factor (BMF) and trophic magnificationfactor (TMF), have not been used explicitly, even thoughthey are better descriptors because they incorporate thepotential for dietary uptake and biotransformation in theaggregate measure of accumulation. Similarly, under theSC, toxicity is simply stated as ‘significant adverse… effects’or ‘high toxicity’ with no indication of what ‘significant’ or‘high’means.Criteria for classification of pesticides or other chemicals

as PBT under EC Regulation No. 1107/2009 or theprogram for REACH, which entered into force on 1 June2007 (Table 2), are similar to those used for POPs (Table 1),but LRT is omitted and the triggers for P and B are morestringent. As has been pointed out elsewhere, criteria usedto classify POPs and PBTs are single values [17] and theclassification process, particularly for pesticides under ECRegulation No. 1107/2009, does not consider additionaldata on intensive properties as well as environmental fateand toxicity that are available for pesticides. Since REACHdoes not have jurisdiction over pesticides, such as CPY,

LRT substances under the SC and UNECE

Potential for long-range transport(LRT)

criteria other than ‘significantan health and/ortal effects’ (in Article 8, 7 (a))

Air: DT50 > 2 days. Monitoring ormodeling data that shows long-rangetransport via air, water, or biota

Concentrations of potential concerndetected in remote locations

r this is is for dissipation or for degradation (transformation).

Table 2 Criteria for the categorization of compounds as PBT under REACH or EC Regulation No. 1107/2009


Marine water: t½ >60 days BCF >2,000 in aquaticspecies

Chronic NOEC <0.01 mg/L or is a carcinogen, mutagen, or toxic for reproduction, or otherevidence of toxicity

Fresh water t½ >40 days

Marine sediment: t½>180 days

Freshwater sediment: t½>120 days

Soil: t½ >120 days

From [7,8].


classification of chemicals in commerce under this legalinstrument is not further discussed, except for purposes ofcomparison.Assessment of chemicals to determine if they should be

classified as POPs under the SC is a lengthy processinvolving nomination of candidate substances by a partyor group of parties, review of data, and final recommenda-tions from a review committee (the POPs RC) [2]. Thisprocess is open, but there is no definitive framework forclassification and criteria are sometimes inconsistentlyapplied [24]. After a COC is classified as a POP, it is addedto Annex A (elimination), B (exemptions), or C (uninten-tional) of the SC. Since, under the SC, the UN does nothave regulatory jurisdiction over the parties (signatory na-tions), ratification of classification and any subsequentphase-out and/or banning of the manufacture and use ofthe POPs are undertaken individually by the parties. In fact,the USA, which is a major player in the manufacture anduse of chemicals, is not a signatory of the SC. Phase-outcan take several years because time is provided for users tofind substitutes and, in some cases, such as DDT, specificexemptions for continued availability may be granted foracceptable purposes such as for the protection of humanhealth.Within the European Union (EU), criteria for assess-

ment of plant protection products (PPPs) for PBT or POPproperties are given in EC Regulation No. 1107/2009 andassessments of individual COCs are conducted by Rappor-teur Member States (RMS) of the EU in much the sameway as registration of new active ingredients. There is noexplicit framework or guidance for classification otherthan a draft document from the EU Directorate Generalfor Health and Consumer Affairs (DG SANCO) [21], and,unlike REACH [7], there is no guidance for how studiesare to be evaluated or how the relevance of the data inthese studies is to be assessed. REACH recommends theuse of a WoE approach for assessing data on chemicals incommerce but does not describe how this is to be done.EC Regulation No. 1107/2009 does not mention WoE atall. Under EC Regulation No. 1107/2009, if a PPP is classi-fied as P, B, and/or T, exceeding trigger values for allthree criteria ultimately results in a ban of the use ofthe product in the EU. Exceeding two of the criteria

results in the PPP being listed for substitution withalternative pesticides that do not exceed establishedtrigger values.Since pesticides are designed to be toxic to at least some

groups of organisms, the criterion for assessment of toxicityis likely to capture all pesticides. Therefore, classification ofPPPs as PBTs under this scheme is primarily driven by theP and B. The trigger for classification as T (Table 2) is‘Chronic NOEC <0.01 mg/L or is a carcinogen, mutagen,or toxic for reproduction, or other evidence of toxicity.’The NOEC trigger is strictly for aquatic organisms, whichwill bias classification of insecticides as T because they areusually equally or more toxic to crustaceans than they areto insects. Few PPPs are deliberately applied to water, sofate and movement in the environment are importantdrivers of concentrations in water, yet these factors are notconsidered in classification. Finally, there is no consider-ation of toxicity for terrestrial species, despite the fact thatit is to this environmental compartment that most pesti-cides are routinely applied.

Problem formulationRegistration and re-registration of pesticides in most juris-dictions require a large number of expensive and demand-ing studies under both laboratory and field conditions onfates and effects of pesticides in the environment as awhole. As illustrated in Figure 1, assessments of risk usedduring registration of pesticides are focused on protectionof non-target organisms that enter and use the treated areasas habitat or that might be affected if the pesticide movesoff the target agroecosystem. The assessment of riskconducted during registration includes characterization ofbioaccumulation and metabolism in key species andtoxicity to a range of species. In the process of decision-making, toxic potency to non-target organisms is consideredand combined with exposures inside and outside of theagroecosystem to assess the acceptability of risks from theuse of the pesticide.Risk, which is the relationship between toxicity and ex-

posure, is not considered in the probabilistic sense in theclassification of chemicals as POPs. The review processunder the SC is designed to ‘evaluate whether a chemicalis likely, as a result of its long-range environmental

Figure 1 Illustration of the basis for risk assessment of pesticides.


transport, to lead to significant adverse human health and/or environmental effects, such that global action iswarranted’ [Annex E in 2], whereby the process is based ona deterministic hazard quotient (Annex E (b)). Under ECRegulation No. 1107/2009, binary criteria are used tocategorize substances by comparing the properties of thecompound to simple threshold or trigger values. Thissimplistic approach is appropriate for lower tier screeningor priority setting, but it is not appropriate as a final step indecision-making.Goals for protection, sometimes referred to as ‘assessment

endpoints,’ are usually either identified explicitly or implicitlyin regulations. In terms of humans and the environment, thegoals of EC Regulation No. 1107/2009 are ‘…to ensure a highlevel of protection of both human and animal health and theenvironment and at the same time to safeguard the competi-tiveness of Community agriculture.’ [8]. In the absence ofmore specific goals, it is logically assumed that the concernis for the general environment, not for a particular local sce-nario. For classification of COCs as POPs under the SC, thisis a global concern. POPs identified under the SC are notpermitted for use in the EU, so the environment of concernunder EC Regulation No. 1107/2009 is that within the EU,which is the jurisdiction of regulation. With this in mind,characterization of P for the regional as well as the global en-vironment was accomplished by refinement of the general-ized assessment presented previously [15].

Properties of chlorpyrifosThe physical and chemical properties of CPY have beensummarized relative to assessment of risk to the

environment of the use of this product in agriculture in theUSA [15,20,25] and are thus not repeated here. The focusof the following sections is on characterizing the P, B, andT properties of CPY in relation to criteria for classificationunder the SC and EC Regulation No. 1107/2009. SinceAnnex II 3.3 of EC Regulation No. 1107/2009 specificallyincludes metabolites, they were included in the assessment.Under environmental conditions, several transformation

products of CPY are formed [20] and have been consideredin the assessment of risks [26]. CPYO is assessed in thisdocument, but trichloropyridinol (TCPy) has not beenidentified as a metabolite of toxicological or environmentalconcern [26,27] and was excluded from consideration here.Because of similarities in the structure of TCPy to

trichlorophenol, from which dioxins and furans are knownto be formed, the possibility of this occurring with CPYwas considered. Dibenzo dioxins and furans were notdetected (limit of detection (LOD) 0.006 to 0.0008 ng/g)in formulations of CPY [28]. A recent study reported theformation of 2,3,7,8-tetrachloro-1,4-dioxino-[2,3-b:5,6-bʹ]dipyridine (TCDD-Py), an analog of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), when pure (2 mg) CPY waspyrolyzed in sealed ampules at 380°C, but not 300°C or340°C, for 15 min in the presence of 10 mL of air [29].Greater amounts of TCDD-Py (≈100-fold) were formedfrom pure TCP under all of the above conditions. TCDD-Py is unstable under the conditions of synthesis of CPYfrom TCP [30], suggesting that, even if it is formed, it willnot become a contaminant in the commercial product. In astudy of effects of combustion on the fate of TCP, only TCPand CO2 were identified in smoke from cigarettes containing


residues (900 ng/cigarette) of 14C-labeled TCP. Detectionlimits for hexane-extractable non-polar compounds (2% oftotal radioactivity applied) such as TCDD-Py were notprovided [31].Dibenzo-p-dioxins have been observed in formulations

of chlorinated pesticides, such as 2,4-D, exposed tosunlight [32]. A study of photodegradation of 14C ring-labeled CPY in buffered and natural waters treated with0.5 and 1 mg CPY/L did not reveal the presence of polarcompounds except CPY and dichloropyridinyl phosphoro-thioate esters and 96% of the degradates formed werepolar compounds [33]. Dioxins such as TCDD are rapidlyphotolyzed by sunlight in the presence of a hydrogendonor with a half-life of the order of hours [34]. Thus, ifTCDD-Py was formed in sunlight, it might be expected tobe photolabile and non-persistent in the environment.A search of the literature failed to reveal the isolation

and identification of TCDD-Py in the environment, eitherbecause it is not formed in detectable amounts, because itis rapidly degraded, or because it has not been analyzedfor. The only papers that reported on its formation and/orbiological activity [29,35] did not conduct analyses ofenvironmental samples. They also did not test whetherTCDD-Py was formed by photolysis from CPY or TCP.TCDD-Py is only moderately toxic to rats. It has an oral

median lethal dosage (LD50) of 300 mg/kg body mass(bm) in rats (strain unspecified), about four orders of mag-nitude less toxic than TCDD, which has an LD50 of 0.022to 0.045 mg/kg bm [36]. Tests in female Sprague–Dawleyrats exhibited loss of body mass but no lethality or grosspathological findings at an even greater acute oral dose of600 mg/kg bm [37]. The same study reported no evidenceof chloracne on the ears of NZ white rabbits treated 18times with a solution containing 50 mg TCDD-Py/L [37].On the basis of this evidence, we conclude that TCDD-

Py is either not formed from CPY or TCP under normalconditions of use or the amounts formed are so small thatit has escaped notice in the analyses of bioaccumulativesubstances in environmental samples. In addition, the rela-tively low toxicity of TCDD-Py indicates that, even ifformed in the environment, it presents little risk to humansor the environment. Thus, TCDD-Py was not included inthe following assessment.

Analysis planSince there was little guidance in categorizing POPs andPBTs [with the exception of 21], WoE was used to selectthe most appropriate data for inclusion in the assessment.WoE is a phrase that is widely misused in the literature[16] and has been applied to a number of procedures forassessment of risk. Here, WoE is used as a quantitativeprocedure for evaluating the strength of studies, based onhow they were conducted, and the relevance of the datafrom the studies to characterization of the COC, CPY, as a

POP or PBT chemical. Strength of studies was evaluatedby a numerical scoring system (see the ‘Quality assurance’section). Relevance was also assessed, particularly in thecase of persistence, where studies were conducted at verylarge rates of application, such as for control of termites,which are inconsistent with current uses, and in the caseof bioconcentration, where studies were conducted atexposures greater than the maximum solubility of theCPY in water. All of the available data were evaluated (seeAdditional file 1), and then, on the basis of strengths ofthe studies, those studies that provided the most robustdata were selected for inclusion in the assessment of thePBT properties of CPY. Studies conducted under non-relevant conditions were then excluded to provide themost robust and relevant data for the characterization.This procedure is different from the assessment con-ducted by Mackay et al. [15] where all data were used,regardless of their strength or relevance.Because extreme (worst-case) values observed in specific

conditions are not representative of all situations, meanvalues were used for comparison to the criteria for classifi-cation, a process which has been recommended in the lit-erature [17] and the draft guidance of SANCO [21].Because most of the processes related to P or B at environ-mentally relevant concentrations are driven by first-orderor pseudo-first-order kinetics and thus are lognormallydistributed, geometric mean values are the most appropri-ate for comparing triggers for classification and were usedin this assessment.Since persistence of CPY in the environment is

dependent on its unique properties as well as the proper-ties of and conditions in the surrounding environment, inthe context of global persistence, all acceptable values forassessment of CPY as a POP were combined [15]. Becauseof the regional focus of EC Regulation No. 1107/2009,data for persistence were segregated into studies from theEU and from other regions. These data were analyzedseparately.In addition to consideration of characteristics related to P,

B, and T, other lines of evidence were also used as a meansof corroboration of the more simple criteria for classifica-tion. As in the SC, one line of evidence was based on re-ports of bioaccumulation of CPY in organisms in the field.Concentrations in aquatic systems in the USA have beenthoroughly reviewed [25] and were not included in the as-sessment presented here other than in the context of asses-sing exceedences of criteria for toxicity and their rapidresponse to changes in pattern of use.

Sources of dataAn exhaustive review of the literature was conducted insupport of an ecological risk assessment of CPY [14, etseq.], and results were compiled into an electronic database,which formed the basis for the information used in this


report. The extensive search of the available literature wasconducted by using Web of Knowledge®, a database withaccess to a number of other digital collections and data-bases. In addition, searches were conducted with GoogleScholar using keyword string searches to access otheravailable peer-reviewed resources. Recent reviews of theliterature on the properties of CPY [15,20] provided anoverview of pertinent studies. Also included in thereviewed body of work were relevant unpublished studiesfrom Dow AgroSciences and its affiliates, which wereprovided to the authors in their original forms.From the results of the extensive literature search, those

studies judged to be directly related to persistence and/orbioaccumulation of CPY were retained for further assess-ment. These included studies on persistence in sediment,soil, and water, performed under laboratory or field condi-tions, and studies from any international jurisdiction. Intotal, 41 papers or reports on bioaccumulation of CPY inbiota and 90 papers or reports on persistence of CPY insoil, sediment, and/or water were included in the scoringevaluation. Data on toxicity to aquatic organisms werepreviously screened for quality [38] and were used in thisassessment without further characterization.

Quality assuranceThose papers retained from the literature search were sub-jected to a WoE assessment with the aim of identifying thosestudies that should form the basis of the final report. Scoringused in our evaluation was based on criteria developed forinclusion of data in the International Uniform ChemicalInformation Database (IUCLID) [39] and more currentupdates. The system was augmented by application ofnumerical scores as has been done previously for selectionof toxicity data for CPY [38]. Specific scoring criteria weredeveloped for each type of exposure, including bio-accumulation in sediment-dwelling organisms, aqueousbioconcentration, bioaccumulation from dietary exposure,persistence in soil, persistence in sediment, and persist-ence in water. These criteria were based on OECDmethods for testing [40] under the relevant conditions(OECD Methods 305, 308, 309, and 315). Criteria assessedthe strength of the methods used in each study, and ascore of 0, 1, or 3 was assigned for each criterion, indicat-ing that the criterion was not met, was attempted but notfully met, or was fully achieved, respectively. The scoringmatrices are provided (see Additional file 1: Table S1).A consensus score was also available as part of the

strength of methods as a mechanism to adjust scores forthose few studies where an invalidating error was notcaptured by the standard matrix for evaluation. Inaddition to assessing the strength of methods, the rele-vance of the study was also assessed by setting limits forrates of application that would be considered environmen-tally relevant (based upon current recommended use rates

[20]) and assigning a score of 0, 1, or 3 for relevance. Afull score was assigned if the rate of application wasequal to or less than the relevant rates of 200 μg/L (accumu-lation in water), 1,000 μg/L (persistence in water), or 8 mg/kg (accumulation or persistence in soil/sediment), a score of1 was assigned if the rate was within 25% of the set value(i.e., ≤250 μg/L, 1,250 μg/L, or 10 mg/kg), and a score of 0was assigned if the rate was more than 25% above the setvalue for environmental relevance. Criteria for relevancealso evaluated whether a description of variance was pro-vided, whether dietary spiking was performed at appropri-ate concentrations (residues not exceeding 5 μmol/g) and/or whether BAF was calculated kinetically from the depura-tion rate constant, as appropriate for each type of study.Briefly, the process of evaluation proceeded as follows: a

study that had been identified through review of the litera-ture and screening process was scored according to the ap-propriate matrix. Scores were recorded, along with adescription of the study methods, and a summary of thereasons for the assigned score for each criterion. Where aspecific study element or criterion was not explicitlyaddressed in the paper and could not be readily inferredfrom the results, it was assumed that the criterion was notmet and a reduced score was assigned. If a missing elementmade the assessment impossible or if it was not possible toscore a particular criterion for an individual study, that cri-terion was omitted from the scoring. This most commonlyoccurred for the use of a solvent in studies of bioaccumula-tion, where a solvent was not required, but in the casewhere it was used, it should be one from an approved list.In cases where no solvent was used, that criterion wasomitted from the assessment.In total, assessments were completed for 44 bioaccumu-

lation studies and 90 persistence studies, and the scoresare summarized in Additional file 1: Tables S2 through 5.It was not possible to obtain a copy of one report on bio-accumulation and two papers on persistence that hadbeen identified during the review of the literature, so thesestudies could not be assessed. After assessment, thosestudies that received scores of less than 50% for strengthof methods were excluded for the purposes of this assess-ment. In total, 23 studies of bioaccumulation of CPY and44 studies of persistence of CPY were included in the finalassessment.

Main textPersistencePersistence was assessed by determining the half-livesfor degradation in soils, sediments, and surface waters.Information from both laboratory and field studies wasconsidered. In the case of field studies, some losses mighthave occurred via volatilization; however, this is a realisticloss process affecting exposure in the field. Thus, thesedissipation data are appropriate for inclusion in the


assessment as long as the degradation in the compartmentinto which partitioning occurs, in this case air, is consideredas well. Studies conducted in the laboratory at normalranges of temperature (15°C to 35°C) were included in theassessment because these temperatures were representativeof the surface layers of the soil in the regions from whichthe samples were obtained. Since the relatively large KOC

of CPY limits mobility in agricultural soils, surficial tem-peratures are more representative of the environment inwhich CPY would be expected to occur. Data from fieldstudies were assumed to have been conducted at realistictemperatures.Use of a half-life implies first-order kinetics, but most en-

vironmental degradation processes are of second order inthe concentration of the chemical and the concentration ofthe reactant, either a chemical or the number of microor-ganisms. Concentrations of reactants can vary widely; thus,half-lives are expected to vary considerably, especially infield studies. Use of extreme values for assessment purposescan be highly misleading since they likely reflect unusuallysmall reactant concentrations. The geometric mean wasused in this assessment as a more rigorous approach and isrecommended for assessment of PBT [21].

SoilIn soils, CPY can be degraded by hydrolysis and also micro-bial transformation. Half-lives for dissipation from soils viaall pathways ranged from 1.1 to 1,576 days (see Additionalfile 1: Table S2). There were several outliers that wereexcluded from the assessment because the application rateswere large (i.e., 1,000 mg/kg for control of termites) [41]and were phased out in 2000. Lesser rates of application

Figure 2 Half-life values measured under laboratory conditions for chlocations. Geometric means are indicated by vertical arrows.

(10 and 100 mg/kg) were included in the assessment. Stud-ies of CPY in soils were divided into those conducted underEuropean conditions and those conducted with soils fromother areas of the world. Studies were also stratified bywhether they were conducted under laboratory or fieldconditions.For European soils [42,43] and non-European soils

(Figure 2) [41,44-50] studied under laboratory condi-tions, the geometric means were 73 and 21 days,respectively. These geometric means do not exceed thecriterion for classification as a POP under the SC(180 days) or as persistent under EC Regulation No.1107/2009 (120 days). The geometric mean half-life forall laboratory-based data for soils without exclusion ofstudies was 32 days [15], also less than the criteria forPOPs or PBT.Geometric means of half-lives derived from field studies

in European soils [51-57] and non-European locations[44,58-66] (Figure 3) were 20 and 13 days, respectively.None of the geometric means for dissipation of CPY in soilsunder field conditions exceeded the threshold to be classi-fied as being persistent in soils under the SC or EC Regula-tion No. 1107/2009. The geometric mean half-life for allfield-based data for soils without exclusion of studies was22 days [15], also less than the criteria for POPs or PBT.Given the relatively short half-lives observed in soil,

CPY is very unlikely to accumulate in soils as a result ofrepeated use in agriculture. Thus, treated soils will not actas a reservoir for other matrices such as water. This isconsistent with rapid decreases in concentrations of CPYin surface water after changes in patterns of use (see the‘Measured concentrations in surface waters’ section).

lorpyrifos (CPY) in soils from European and non-European

Figure 3 Half-life values measured under field conditions for chlorpyrifos (CPY) in soils from European and non-European locations.Geometric means are indicated by vertical arrows.


SedimentIn sediments, under laboratory and field conditions, thehalf-life of CPY ranged from 1 to 223 days (see Additionalfile 1: Table S3). The geometric mean of all studies was29 days. When only those studies that scored in the top50% of studies were included, the geometric mean was25 days. When studies conducted with European andnon-European sediments were considered separately(Figure 4), the geometric means were 40 and 19 days,respectively. None of the geometric means exceeded thethreshold for classification of CPY in sediments as being


persistent under EC Regulation No. 1107/2009. Even themaximum values of 200 and 230 days were only slightlygreater than the 180 days necessary to classify CPY asbeing persistent in sediment. The geometric mean half-lifefor all studies (without exclusions) was 38 days [15], whichis also less than the criteria for POPs or PBT (180 and120 days, respectively).

WaterIn water, CPY can be degraded abiotically by aqueoushydrolysis, photolysis, and microbial transformation.

lorpyrifos (CPY) in sediments from European and non-European


The following sections summarize data on persistence inwater.

Decomposition in aquatic systems In water, hydrolysisis one of the primary mechanisms of degradation of CPY.Aqueous hydrolysis of CPY is inversely proportional to pH[67] (see Additional file 1: Figure S1). In aquatic systems at25°C, half-lives of 73, 72, and 16 days were measured atpH 5, 7, and 9, respectively [summarized in 67]. In distilledwater, in the absence of light and microorganisms, the half-life ranged from as little as 0.01 to 210 days, depending onpH [68-70] (see Additional file 1: Table S4D). Data for half-life measured in distilled were not included in the as-sessment as this matrix is not environmentally realistic.At pH >6 to <10, the half-life of CPY ranged from 4.5to 142 days. When the pH was greater than 10, thehalf-life was as short as 0.01 day. In this assessment,hydrolysis in natural water was considered realistic andwas included, regardless of pH.Half-lives of 22 to 51 days have been reported from me-

tabolism studies conducted in aerobic aquatic systems[71,72]. In the presence of natural sunlight, in sterile pH 7phosphate-buffered solution, the half-life was 30 days [33].Thus, dissipation attributable to photolysis was not muchdifferent from that attributable to hydrolysis alone. Intheir simulations of the dynamics of CPY in aquaticsystems, the US EPA [27] used an aqueous hydrolysis half-life of 81 days at pH 7.0. In surface waters measured inthe laboratory, half-lives of CPY ranged from 1.29 to126 days [69,70,73,74] (see Additional file 1: Table S4B).In an analysis of half-lives in water-only studies with

WoE scores greater than 50%, the geometric mean half-lifefor all waters tested in the laboratory was 6 days. Thegeometric mean half-life for all laboratory-based datawithout exclusion of studies was 21 days [15]. When studiesconducted with waters from European locations (Figure 5and Additional file 1: Table S4A) [75,76] and non-Europeanlocations (Figure 5 and Additional file 1: Table S4B)[69,70,73,74] were considered separately, the geometricmeans were 2.2 and 11 days, respectively. There were nofield data from the EU, but the geometric mean of field datafrom non-EU locations [77,78] was 6 days (see Additionalfile 1: Table S4C). None of these geometric mean valuesexceeds the criterion for persistence (60 days) in water forclassification as a POP under the SC or as persistent(40 days) under EC Regulation No. 1107/2009.

Overall evaluation of persistenceThe geometric means of half-lives of CPY in soils, sedi-ments, and surface waters were less than the thresholds forclassification of a compound as being persistent in soils,sediments, and water under the SC or EC Regulation No.1107/2009. These conclusions are the same as those

reached in an assessment of all the data on persistence inthe earlier assessment by Mackay et al. [15].No studies on persistence CPYO have been reported in

the literature, and it has not been detected as a metabolitein studies on dissipation of CPY in soils [15]. This, alongwith its short half-life in water (4.7 days at pH 7), supportsthe conclusion of Mackay et al. [15] that CPYO is less per-sistent than the parent compound, CPY, and thereforedoes not trigger the criterion for persistence under the SCand EC Regulation No. 1107/2009.

BioaccumulationThe major focus of assessing bioaccumulation under theSC (POPs) and EC Regulation No. 1107/2009 (PBT) is onconcentration from the matrix into the organism as aBCF. Data for BCF (and BAF and biota-sediment accumu-lation factor (BSAF)) from the literature were selectedbased on the quality of the study and relevance of theexposure concentration (see Additional file 1: Table S5).These data are a subset of a larger data set from Mackayet al. [15]. BCF data for fish were separated from otheraquatic organisms. For an amphibian, invertebrates, andplants, BCF, BAF, and BSAF were taken as equivalent forthe purposes of analysis and values are presented graphic-ally (Figure 6). As for toxicity values (below), all data werecombined in the analysis.Empirical values for BCFs for fish ranged from 0.6 to

5,100 [79-94] (see Additional file 1: Table S5A). Fromthe distribution, the smallest value was clearly an outlierand was omitted from the calculation of the geometricmean and the regression. The geometric mean value forBCF for fish was 853, less than the criterion for ECRegulation No. 1107/2009 (2,000) and the SC (5,000).BCFs are often estimated from the octanol-water parti-

tion coefficient (KOW), especially when there is a lack ofempirical data. In the case of CPY, KOW is approximately100,000 [15]. Thus, a fish containing 5% lipid would beexpected to have a BCF of approximately 5,000, which is atthe extreme of empirical observations. This suggests thatCPY is subject to loss processes from fish in addition torespiratory loss, the obvious process being metabolic bio-transformation, but growth dilution and egestion may alsoapply.The BCF (and BAF and BSAF) for invertebrates and

plants (see Additional file 1: Table S5B) ranged from 3.4 to5,700, with a geometric mean of 204. For plants, the great-est value was reported for duckweed (Lemna minor, 5,700)with water lettuce (Pistia stratiotes, 3,000), the third largestand both greater than algae (Oedogonium cardiacuin, 72).The larger values for the two macrophytes might be morereflective of adsorption to the surface of the plant thanuptake into the plant. The BCF values in the invertebratesranged from 3.4 to 691, both in mollusks. The value for theonly amphibian (Ambystoma mexicanum) in the data set

Figure 5 Half-life values measured under laboratory conditions for chlorpyrifos (CPY) in natural waters from European andnon-European locations. Geometric means are indicated by vertical arrows.


was 3,632, which is in the same range as those reported forfishes. The geometric mean value for invertebrates andplants (204) was less than the criterion for EC RegulationNo. 1107/2009 (2,000) and the SC (5,000).No data on biomagnification of the toxicologically rele-

vant metabolite of CPY, CPYO, were found in the litera-ture. Although CPYO is formed in the atmosphere, it isreactive and has a shorter half-life in water (4.7 days atpH 7) than the parent (geometric mean of 2.2 to 11 days)[15]. Despite extensive sampling of surface waters in areas

Figure 6 Graphical presentation of BCF (BAF and BSAF) values for chlindicated by vertical arrows.

of more intensive use, CPYO has never been detectedabove the LOD [25]. Lack of observed bioconcentration orbiomagnification of CPYO is completely consistent withthe greater reactivity of the molecule and its greater solubil-ity and smaller KOW than CPY [15]. All the evidencesuggests that CPYO does not biomagnify.

Concentrations in aquatic biotaConcentrations of chemicals such as CPY in organismscollected in the field are another line of evidence of

orpyrifos (CPY) in aquatic organisms. Geometric means are


bioconcentration and biomagnification. In an extensivesurvey of chemicals in fish from lakes and reservoirs of theUSA [95], residues of CPY were not detected. The methoddetection limit was 59 μg/kg, and 486 samples from preda-tory fish and 395 samples from bottom-dwelling fish wereanalyzed. Concentrations of CPY in samples of fish fromlakes in Western National Parks of the USA were all <1 μg/kg (wet mass; wet. ms.) [96]. Taken together, this is furtherevidence of lack of significant bioconcentration or biomag-nification of CPY into fishes or biomagnification in theaquatic food chain.

Accumulation in terrestrial organismsApart from the detections in plants in montane areas ofCalifornia discussed in Mackay et al. [15], there arereports of detections of small concentrations in plantsfrom more remote areas such as in the panhandle ofAlaska [96] (2.4 ng/g lipid mass (l. ms.) in needles of coni-fers, see the ‘Measured concentrations near areas of use’section). Chlorpyrifos was detected in lichen (0.073 ±0.23 ng/g l. ms.), mushrooms (0.78 ± 0.82 ng/g l. ms.),green plants (0.24 ± 0.47 ng/g l. ms.), caribou muscle(0.57 ± 0.19 ng/g l. ms.), and wolf liver (<0.10 ng/g l. ms.)in Nunavut [97].

Trophic magnificationA characteristic of POPs is biomagnification or trophictransfer in food chains, and this provides another line ofevidence to assess CPY. Only one study was found on move-ment of CPY in food webs. Several current-use pesticideswere measured in a terrestrial food web in the CanadianArctic [97], and CPY was detected frequently in moss andmushrooms (83% to 86%) but at lesser frequency in lichens,willow, and grass (44% to 50%). Concentrations ranged from0.87 ng/g l. ms. in moss to 0.07 ng/g l. ms. in lichen.Concentrations in caribou muscle and total body burdenprovided BMFs of 7.8 and 5.1 compared to lichen; however,the BMF from caribou to wolf was <0.10 (based on concen-trations <MDL). Trophic magnification factors for thelichen-caribou-wolf food chain were all <1 for muscle, liver,and total body burden. That small concentrations of CPYwere found in the Arctic is indicative of some long-rangetransport, but the lack of BMF between caribou and wolfand TMFs of <1 are indicators of no significant trophicmagnification of CPY in the food chain. These additional

Table 3 Toxicity values for CPY in aquatic organisms

Taxon 5th centile (μg/L) 95% CI (μg/L)

Crustaceans 0.034 0.022 to 0.051

Insects 0.087 0.057 to 0.133

Fish 0.812 0.507 to 1.298

Amphibians Too few species for a SSD, range was 19 to a quest

Plants Too few species for a SSD, range was 138 to 2,000

lines of evidence support the laboratory and microcosmdata, which indicate that CPY does not trigger the criterionfor bioaccumulation under the SC or EC Regulation No.1107/2009.

ToxicityToxicity of CPY to aquatic organisms has been reviewed indetail previously in Giddings et al. [38], to birds in Mooreet al. [98], and to the honeybee in Cutler et al. [99]. Ratherthan repeat this information here, the reader is referred tothese papers and their relevant supplemental information.The following sections summarize the toxicity data anddiscuss this in relation to the classification criteria for POPsand PBTs.

Acute toxicity in aquatic organismsBecause CPY dissipates and degrades rapidly in aquatic en-vironments and is only present for short durations (≤4 days),data on acute toxicity were selected as the most appropriatefor assessment of risks in aquatic systems [38]. There werenumerous published studies on laboratory toxicity tests foraquatic organisms. These data were screened for qualityand a subset of the higher quality and most relevant studieswere used in the assessment [38]. Toxicity values wereanalyzed as distributions (species sensitivity distributions(SSDs)) using SSD Master Version 3.0 software [100] and5th centiles (HC5 concentrations) used to characterize tox-icity of CPY to major taxa (Table 3).These acute toxicity values were not separated by type of

medium (saltwater or freshwater) or origin of the species(tropical, temperate, Palearctic, or Nearctic). Analysis of thelarge amount of toxicity data available for CPY has shownthat there are no significant differences in sensitivitybetween these groups [101]. Thus, these data are appropri-ate for classification in the global context (POPs) and in theregional context (PBT).

Toxicity in aquatic meso- and microcosmsSeveral studies of effects of CPY have been conducted inaquatic meso- and microcosms (cosms) and were reviewedin Giddings et al. [38]. These studies were conducted in vari-ous jurisdictions and climatic zones, including Europe(Netherlands and Mediterranean locations), the US Midwest,Australia, and Thailand. Half of the 16 studies reported no-observed-adverse-effect concentrations (NOAECeco) values

Comments

Based on 23 species with a range of 0.035 to 457 μg CPY/L

Based on 17 species with a range of 0.05 to >300 μg CPY/L


ionable value of 5,174 μg CPY/L for three species

μg CPY/L


as ‘less than’ values. For the eight studies in cosms whereNOAECecos were available, all were ≥0.1 μg/L and the geo-metric mean was 0.14 μg/L. The NOAECeco is based on ob-servation of short-term effects in some sensitive organisms,from which there is rapid recovery. For a pesticide, such asCPY, which degrades relatively rapidly in the environment,this is an appropriate measure of a threshold for toxicityunder realistic environmental conditions. Because studies incosms incorporate toxicity of organisms from the region, aswell as processes related to fate that may be influenced bylocal conditions such as climate and hydro-geo-chemistry,there may be regional differences in responses. This was notthe case for CPY; the NOAECeco values were the same re-gardless of location of the study. This not only is consistentwith lack of region-specific toxicity tests but also suggeststhat the fate processes that can influence exposures inaquatic systems are not different between regions. Thus, itwas not necessary to separate the studies in cosms forpurposes of classification of POPs and PBTs.

Toxicity to terrestrial organismsBecause CPY is used as a pesticide to protect crops fromdamage by arthropods, it is obviously toxic to terrestrialstages of insects. This is a benefit of use and is not consid-ered an adverse effect. However, toxicity to valued arthro-pods can be considered an adverse effect and, in the case ofthe honeybee, was characterized in a risk assessment ofCPY [99]. CPY is toxic to the honeybee by direct contact(topical toxicity) with the spray and also via the oral route.The former route of exposure is only relevant when beesare present during or shortly after spraying and is mitigatedby restrictions on the label (see the ‘Reports of toxicityunder current conditions of use’ section below). Topical 24-to 48-h LD50 values for formulated CPY range from 0.024to 0.54 (geometric mean =0.123) μg a.i./bee and 0.059 to0.115 (geometric mean =0.082) μg a.i./bee for the technicalproduct. Oral 24- to 48-h LD50s ranged from 0.114 μg a.i./bee for the technical to 0.11 to 1.1 (geometric mean =0.36)μg a.i./bee for the formulated material [99]. Significanttoxicity to honeybees has only been associated with directexposure during spraying and/or during foraging for nectarand/or pollen in recently treated fields (0 to 3 days postspray). Toxicity has not been reported to be caused by CPYoutside the foraging range of the bees, and residues in

Table 4 Acute and dietary toxicity values for CPYO in birds

Species Observation or feeding time (days)

Bobwhite quail 7 observations

Zebra finch 7 observations

Mallard duck 5 exposure, 8 observations

Bobwhite quail 5 exposure, 8 observations

NA, not applicable.

samples of brood comb have not been casually linked tocolony collapse disorder [102]. There is no evidence tosuggest that small concentrations measured outside theareas of use are toxic to bees or other beneficial insects. Asthe honeybee is found in the EU, North America, and otherparts of the globe, there is no need to consider this speciesdifferently across locations. The conclusions regardingtoxicity to honeybees thus apply to considerations of POPsand PBTs.Toxicity to birds has been characterized previously by

Moore et al. [98]. Because of rapid dissipation of CPY inthe environment and in animals, acute toxicity data wereconsidered most relevant for assessing risks. Acute LD50sranged from 8.55 to 92 (geometric mean =30.5) mg CPY/kg bm in 14 species of birds. Few chronic toxicity data wereavailable, but values for the NOEC and LOEL in themallard duck exposed via diet for 28 days were 3 and18.7 mg CPY/kg bm/day, respectively [98]. Risks of CPY tobirds foraging in treated fields were considered de minimisfor most species, except sensitive species foraging in cropswith large application rates (e.g., citrus). This conclusion wasconsistent with the lack of observed mortality of birds infield studies conducted in North America and the EU. Mam-mals are less sensitive to CPY than birds. Acute LC50 valuesfor laboratory test species ranged from 62 to 2,000 mg CPY/kg bm [103]. Several assessments of risk have concluded thatbirds are more sensitive and more likely to be exposed andare protective of risks from CPY in wild and domesticmammals and that risks to these organisms are de minimis[98,104]. Given de minimis or very small risks fromexposures in areas of use, concentrations of CPY reportedfrom semi- and remote locations present even lesser risks tobirds or mammals.Acute and chronic dietary toxicity values for CPYO have

been measured in birds (Table 4). Although data were few,toxicity values were similar to those for CPY, suggesting,as would be expected from the mechanism of action, thatCPYO has similar toxicity to the parent CPY.

Chronic toxicity in aquatic organismsAlthough there are no known situations where exposuresof aquatic organisms to CPY are long-term, some toxicitytests, such as mesocosm studies, have used repeated expo-sures with no hydraulic flushing to assess the equivalentof repeated exposures. The most sensitive NOEC reported

Toxicity value (mg/kg) 95% CI Reference

LD50 = 8.8 bm 7.2 to 10.7 [105]

LD50≥ 30 bm NA [106]

LC50 = 523 mg/kg diet 363 to 796 [107]

LC50 = 225 mg/kg diet 173 to 292 [108]


for an aquatic organism was from one of these studies:0.005 μg CPY/L for Simocephalus vetulus in a mesocosmexperiment [75]. This value is relevant to assessment ofCPY as a PBT chemical.

Reports of toxicity under current conditions of useThe above conclusions of lack of significant toxicity toaquatic and terrestrial organisms under current conditionsof use in the USA is supported by the very few reports onfish, invertebrate, bee, and bird kills reported in the last12 years [38,98,99]. Where these few incidents haveoccurred, most have been the result of accidents ordeliberate misuse.

Toxicity in relation to classification as a POPThe criterion for toxicity for classification of POPs is‘significant adverse effects’ without a clear definition of‘significant’ or the location of the effects. We have inter-preted that to mean that the use of CPY results in un-acceptable risks in areas outside but not directly adjacentto the area of application (i.e., edge of field). As a pesticide,risks to target organisms in the agricultural field are ac-cepted, but risks to non-target organisms, especially out-side the areas of application, are considered undesirable.None of the data on toxicity of CPY or CPYO to non-

target organisms suggests that there are significant adverseeffects in the environment outside of the areas of use[15,38,98,99]. Even in areas of use, risks to birds and mam-mals are small or de minimis. The data on toxicity of CPYand CPYO to birds, mammals, and aquatic organismsdetermined under laboratory conditions is robust. Thesedata are complemented by studies in aquatic cosms, whichare more representative of exposures in natural environ-ments, showing similar patterns of toxicity and includingspecies that have not been tested in the laboratory underguideline protocols. There are some uncertainties. Not allspecies have been tested and many groups of marinespecies have not been tested at all; however, this is notunique and applies to pesticides other than CPY and tochemicals in general.Considering all of the data on toxicity, we conclude that

CPY and CPYO do not exceed the POPs criterion of‘significant adverse effects’ (Table 1) for toxicity to organ-isms in the environment.

Toxicity in relation to classification as a PBTThe criterion for classification of pesticides as toxic underEC Regulation No. 1107/2009 is ‘Chronic NOEC <0.01 mg/L (10 μg/L) or is a carcinogen, mutagen, or toxic forreproduction, or other evidence of toxicity’ (Table 2). Ashas been discussed before [17], the criterion refers only toaquatic organisms and terrestrial organisms are not consid-ered. The NOEC for S. vetulus (0.005 μg CPY/L) is lessthan the criterion, so CPY would be classified as T. In

addition, the acute toxicity values for CPY for many crusta-ceans and insects, and even some fish, were <10 μg CPY/L[38]. Given that CPY is an insecticide and that crustaceansand insects are the most sensitive taxa [38], this is notunexpected. However, several additional factors that placetoxicity in perspective must be considered. CPY is notapplied directly to water, so exposures in this environmentare indirect and small [25]. Since CPY is not persistent inwater or other environmental compartments, chronictoxicity values are not environmentally realistic or appropri-ate for classification of toxicity. There is robust evidence toshow that CPY is not sufficiently persistent in any environ-mental compartments to justify durations of exposure asso-ciated with chronic toxicity. Thus, it would have beeninappropriate to compare concentrations in remote regionsto those associated with chronic effects of CPY. No chronictoxicity data for CPYO were available; however, it has a rela-tively short half-life in water [15] and has not been detectedin surface waters, even in areas of high use [25].Carcinogenicity, mutagenicity, or reproductive toxicity

of CPY were not assessed in this evaluation, but havebeen assessed in recent reviews by the US EPA as partof the re-registration process. Based on current usepatterns, CPY was not identified as a mutagen, carcinogen,reproductive toxicant, or immunotoxic agent [26]. The verysmall concentrations reported in semi- and remote areasdo not represent a risk to humans through drinking wateror via the food chain.

DiscussionAtmospheric transportThe potential for LRT is considered in both water and air.Since the half-life of CPY in water does not exceed thecriterion for persistence in water (see the ‘Water’ section),it is unlikely that LRT in water would be a significantissue. Thus, the potential for LRT of CPY and CPYO inthe atmosphere was assessed in detail. The criterion forLRT in air under the United Nations Economic Commis-sion for Europe [3] is that the half-life is ≥2 days (Table 1)or that monitoring or modeling data demonstrates long-range transport. Since masses of air containing volatilizedCPY can move, a static determination of the half-life in airis not instructive. The issue is: can CPY persist long enoughto move significant distances from where it is released anddeposit into soils and water at concentrations sufficient tocause adverse effects? Evidence that CPY is subject to LRTis provided in reports of concentrations in air and othermedia at locations remote from sites where CPY is appliedin agriculture [15].The assessment reported by Mackay et al. [15] used a

combination of analyses, including measured concentrationsat locations distant from sources, in conjunction with massbalance modeling. Predictions of atmospheric transport weremade by the use of simple mass balance models such as


TAPL3 and the OECD Tool [15,109,110]. These modelshave been used in regulatory contexts and characterizeLRT as a characteristic travel distance (CTD), which isdefined as the distance that approximately two thirds of theoriginally released mass of CPY or CPYO is transportedfrom the source before it is deposited or transformed.Detailed assessments of the properties of CPY [15,20,111]and its fate in the environment and potential risks [14] havebeen published previously [67,112]. CTDs of several pesti-cides, including CPY, have been estimated [113]. Results ofthese modeling exercises have suggested a CTD of 280 to300 km for CPY if it is assumed that the atmospheric half-life is 12 h, the narrow range being the direct result of closesimilarities between the model equations. As is discussedbelow, this estimate of CTD reflects an unrealistically longatmospheric half-life.

Predicted concentrations in the environmentThe assessment of LRT presented here went beyond de-termination of CTD and the related characteristic traveltime (CTT) and also included consideration of estimatesof concentrations of CPY and CPYO in other environmen-tal media such as rain, snow, and terrestrial phases, as wellas in the atmosphere at more remote locations, includinghigher altitudes [15]. A relatively simple mass balancemodel was developed and used to predict concentrationsin various media at various distances from sources whereCPY was applied in agriculture, which could be comparedto measured concentrations of CPY in air and othermedia. Results of the model can then serve as a semi-quantitative predictive framework that is consistent withobservations.As an example of dissipation of a parcel of air contain-

ing 100 ng CPY/m3, which is typical of concentrations1 km from application sources, a model was developed toassess the concentration as it is conveyed downwind [15].The mass would be decreased as a result of transform-ation processes, primarily reaction with •OH radicals,deposition, and dilution by dispersion. Oxidation resultsin formation of primarily CPYO. By using the TAPL3simulation of a relatively large environmental area and ahalf-life in air of 3.0 h and conservative (longer duration)half-lives in other media and assuming an emission rate toair of 1,000 kg/h, the resulting mass in air is 4,328 kg, theresidence time in air and the CTT is 4.3 h, and the corre-sponding rate constant for total loss is 0.231/h. The CTDof approximately 62 km is the product of 4.3 h and thewind velocity of 14.4 km/h. The rate of transformation is993 kg/h, and the net losses by deposition to water, vege-tation, and soil total about 7 kg CPY/h, which correspondsto a rate constant of 0.0016/h and is less than 1% of therate of degradation. The critical determinant of potentialfor LRT is the rate of transformation from reactions with•OH radicals in air. If the half-life is increased by an

arbitrary factor of 4 to 12 h, as was assumed in [113], theCTD increases to 244 km [15].Results of simulation models predicted concentrations

and partial pressures or fugacities (expressed in units ofnPa) at several distances from application of CPY in typicalagricultural uses. A simple but approximate approach toestimate concentrations of CPY at distances from sources isto use a dispersion model to estimate concentrations atground level from a ground-level source using standard airdispersion parameters [114]. Near the area of application,such as at a distance of 1 km and assuming a 0.1-h air tran-sit time, air concentrations (C1 km) were assigned a value of100 ng CPY/m3 (approximately 700 nPa). Concentrationsof CPY are primarily controlled by rates of evaporation anddispersion rather than reactions with •OH. At a distance of120 km and a transit time of 8.4 h, which is equivalent totwo CTDs, 84% of the volatilized CPY would have beentransformed and the concentration of CPY in air would be0.022 ng CPY/m3 (0.16 nPa). At steady state, rain waterwould have a concentration of 0.1 ng CPY/L and snow aconcentration of 1.5 ng CPY/L. If a very conservative half-life of 12 h for CPY were assumed, the fraction of CPYtransformed would be only 38% and thus greater concen-trations of CPY would persist for longer distances. At a dis-tance of 300 km and a transit time of about 20 h, which isequivalent to approximately five CTDs, 1.0% of the initialmass of CPY would remain because the CPY would havebeen subjected to nearly seven half-lives. Concentrations atthis distance from the source would likely be 0.0003 ngCPY/m3 (0.002 nPa) or less. Concentrations of 0.003 ngCPYO/m3 would be expected. Thus, at this distance fromthe source, CPYO would be the primary product present,at a concentration which is near the typical limit of quanti-tation. Rain, if at equilibrium with air, would be expected tocontain a concentration of 0.001 ng CPY/L and snow0.02 ng CPY/L. Given an assumed half-life of 3 h and thetime to be transported this distance, it is unlikely that,under normal conditions, significant quantities could travelmore than 300 km. Observations of detectable amounts ofCPY at greater distances, such as 1,000 km [115], suggestthat, at least under certain meteorological conditions asmay apply at high latitudes or times of low solar radiationand less production of •OH radicals, the half-life is longerthan was assumed in this analysis. The significant conclu-sion is that partial pressures, fugacities, and concentrationsin air at distances of 100 s of km are expected to be reducedby a factor of a million or more from those within a kmfrom sources.

Measured concentrations near areas of useWhile the vapor pressure of CPY is considered to bemoderate, CPY can be measured in the air during andafter application. In the 12 h following application of theliquid formulation to the surface, approximately 10% to


20% of the applied material volatilizes, but variability isexpected diurnally, with temperature, rainfall, and soil mois-ture content. Sorption then ‘immobilizes’ the CPY and sub-sequent volatilization is slower, with a rate of approximately1% per day that decreases steadily to perhaps 0.1% per dayin the subsequent weeks [15]. Concentrations in air thatexceed 20 ng CPY/m3 have been observed near sources ofapplication in agriculture [15]. Concentrations of CPY in airimmediately above a potato field in the Netherlands at noonin midsummer ranged from 14,550 to 7,930 ng/m3 at 1 and1.9 m above the crop 2 h after application [116]. Thesedecreased to a range of 2,950 to 1.84 ng/m3 after 8 h and to26 to 15 ng/m3 in the 6 days following application. Concen-trations of CPY in air following an application of 4.5 kg/hato turf were in the range of 1,000 to 20,000 ng/m3 [117].This might be a ‘worst case’ in terms of concentrations andrepresents approximately 10% of the saturation concentra-tion in air, i.e., the vapor pressure/RT, where RT is the gasconstant-absolute temperature group. Concentrations ofapproximately 100 ng CPY/m3 are regarded as typical ofareas immediately downwind (approximately 1 km) of ap-plication sites [15].

Measured concentrations and deposition in semi-remotelocationsChlorpyrifos and CPYO have been detected in the envir-onment [15]. Concentrations in the range of 0.01 to 10 ngCPY/m3 that have been reported at distances of up to100 km from sources are considered to be regional.Concentrations less than 0.01 ng CPY/m3 have beenobserved in more remote areas. Approximately 70% of thedata for concentrations in air were in the range of 0.01 to1.0 ng CPY/m3. For rain, the greatest frequency (40%) wasin the range 1 to 10 ng CPY/L. Concentrations of CPY insnow exhibited similar patterns, but with more concentra-tions in the range 0.01 to 0.1 ng CPY/L [15].Apart from the detections in plants in montane areas of

California discussed in Mackay et al. [15], there are reportsof detections of small concentrations from more remoteareas, such as the panhandle of Alaska [96]. Concentrationsof CPY in lichen were <MDL (1 ng/g l. ms.) and mean con-centrations as great as 2.4 ng/g l. ms. in needles of conifersin Denali National Park, Wrangell-St. Elias National Parkand Preserve, Glacier Bay National Park, Katmai NationalPark and Preserve, the Stikine-LeConte Wilderness, and theTongass National Forest in samples collected between 2002and 2007. The amounts of CPY measured were small incomparison to those reported at locations closer to regionsof release [15] and are not suggestive of the transport oftoxicologically significant amounts of CPY. It is thus not sur-prising that small but detectable concentrations can befound in remote locations such as Svalbard [113,115]. Thelargest concentration in a remote location was found in icecorresponding to the 1980s from Svalbard. While that

concentration was 16 ng CPY/L, concentrations measuredmore recently are generally <1 ng CPY/L. Residues ofCPY and CPYO were absent in the surface section of thecore, representing 1990 to 1998 [115], despite this likelybeing the period of greatest global use. A survey ofconcentrations of CPY in a north–south transect of lakesin Canada reported the presence of residues of CPY [113].Greater concentrations were reported in lakes with agri-cultural inputs (mean =0.00065 μg/L). Concentrations andfrequency of detection decreased with increasing latitude,with mean concentrations of 0.00082, <0.00002, and0.00027 μg/L for remote mid-latitude, subarctic, and arcticlakes, respectively. These were grab samples and the tem-poral profile of exposures are not known; however, allconcentrations are several orders of magnitude less thanthe HC5 for crustaceans (0.034 μg/L, Table 3) or theNOAECeco of ≥0.1 μg/L (see the ‘Toxicity in aquaticmeso- and microcosms’ section) for repeated exposures inmicrocosms.

Measured concentrations in surface watersChlorpyrifos (but not its toxicologically significant productof transformation, CPYO) has been detected in surfacewaters, particularly in areas of intensive use [25]. Inseveral regions of the USA, these concentrations havedecreased since the late 1990s and early 2000s [118-120],most probably as a result of changes in patterns of use[25]. Thus, rather than an upward trend in concentrations,the frequency of detection and the concentrations mea-sured in surface waters have declined. This is not indica-tive of persistence in the environment.

ConclusionsWhile both CPY and CPYO are classified as “toxic”, basedon the assessment of persistence and bioaccumulation, allthe lines of evidence suggest that neither would be classi-fied as persistent or bioaccumulative under the SC or ECRegulation No. 1107/2009. Based on the analysis of LRT,neither CPY nor its most toxic transformation product,CPYO, would be transported at sufficiently great concen-trations to cause adverse effects in humans or the environ-ment in remote areas. Based on the simple criterion fortoxicity in EC Regulation No. 1107/2009, CPY (and byextension, CPYO) would be classified as toxic; however,when a more refined assessment of ‘risk’ is consideredinstead of ‘hazard,’ it does not present unacceptable risks tohumans or organisms in the environment. Based on thewording of the SC, CPY and CPYO do not present a signifi-cant adverse risk to humans and the environment. Theseconclusions are based on the selection of higher qualitydata but are similar to those reached by inclusion of all thedata [15].


Additional file

Additional file 1: Supplemental information for Giesy et al. 2014[14]. The additional file provides one figure and several tables of rawdata related to the criteria for WoE, persistence, and bioaccumulation.

AbbreviationsB: bioaccumulative; BAF: bioaccumulation factor; BCF: bioconcentrationfactor; bm: body mass; BMF: biomagnification factor; BSAF: biota-sedimentaccumulation factor; COC: chemical of concern (substance of concern);CPY: chlorpyrifos; CPYO: chlorpyrifos oxon; CTD: characteristic travel distance;CTT: characteristic travel time; KOC: water-soil partition coefficient correctedfor the amount of organic carbon in the soil; KOW: octanol-water partitioncoefficient; l. ms.: lipid mass; LC50: lethal concentration for 50% of testindividuals; LRT: long-range transport; NOEC: no-observed-effect concentration;nPa: nanoPascals; P: persistent; PBT: persistent, bioaccumulative, and toxic;POP: persistent organic pollutant; REACH: Registration, Evaluation, Authorisationand Restriction of Chemicals; SC: Stockholm Convention; T: toxic; t½: half-life;TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD-Py: 2,3,7,8-tetrachloro-1,4-dioxino-[2,3-b:5,6-b′] dipyridine; TCP: trichlorophenol; TCPy: trichloropyridinol;TMF: trophic magnification factor; UNEP: United Nations EnvironmentProgramme.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsThe authors JPG, KRS, and DM contributed directly to the concepts, analyses,development of conclusions, and writing of the paper. JA provided technicalassistance and assessment of the strength and relevance of the studies, andKRS formatted and prepared the paper for submission. All authors read andapproved the final manuscript.

AcknowledgementsFunding for this assessment was provided by Dow AgroSciences, LLP, USA.The opinions expressed in this paper are those of the authors alone. All ofthe references are available from publishers or from the authors except forthose reports which are considered to contain confidential businessinformation. These reports have been provided to the appropriate regulatoryagencies for use in their reviews and deliberations relative to chlorpyrifos. Ifreaders wish to obtain specific information contained in these reports,requests will be passed on to the registrant on a case-by-case basis. JPG wassupported by the Canada Research Chairs Program, a Visiting DistinguishedProfessorship in the Department of Biology and Chemistry and State KeyLaboratory in Marine Pollution, City University of Hong Kong, the 2012 ‘HighLevel Foreign Experts’ (#GDW20123200120) program, funded by the StateAdministration of Foreign Experts Affairs, the P.R. China to Nanjing University,and the Einstein Professor Program of the Chinese Academy of Sciences.

Author details1Department of Veterinary Biomedical Sciences and Toxicology Centre,University of Saskatchewan, Saskatoon, SK S7B 5B3, Canada. 2Centre forToxicology, School of Environmental Sciences, University of Guelph, Guelph,ON N1G 2 W1, Canada. 3Centre for Environmental Modelling and Chemistry,Trent University, Peterborough, ON K9J 7B8, Canada. 4Stantec, 603-386Broadway Ave, Winnipeg, MB R3C 3R6, Canada.

Received: 3 January 2014 Accepted: 6 October 2014

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doi:10.1186/s12302-014-0029-yCite this article as: Giesy et al.: Evaluation of evidence that theorganophosphorus insecticide chlorpyrifos is a potential persistent organicpollutant (POP) or persistent, bioaccumulative, and toxic (PBT). EnvironmentalSciences Europe 2014 26:29.

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DISCUSSION Open Access

Evaluation of evidence that the organophosphorusinsecticide chlorpyrifos is a potential persistentorganic pollutant (POP) or persistent,bioaccumulative, and toxic (PBT)John P Giesy1, Keith R Solomon2*, Don Mackay3 and Julie Anderson4

Abstract

A number of chemicals, including several organochlorine pesticides, have been identified as persistent organicpollutants (POPs). Here, the properties of chlorpyrifos (CPY; CAS No. 2921-88-2) and its active metabolite,chlorpyrifos oxon (CPYO; CAS No. 5598-15-2), are assessed relative to criteria for classification of compounds aspersistent, bioaccumulative, and toxic substances (PBTs). The manufacture and use of POPs are regulated at the globallevel by the Stockholm Convention (SC) and the UN-ECE POP Protocol. Properties that result in a chemical beingclassified as a POP, along with long-range transport (LRT), while understood in a generic way, often vary amongjurisdictions. Under the SC, POPs are identified by a combination of bulk (intensive) properties, including persistenceand biomagnification, and an extensive property, hazard. While it is known that CPY is inherently hazardous, what isimportant is the aggregate potential for exposure in various environmental matrices. Instead of classifying chemicals asPBT based solely on a few simple, numeric criteria, it is suggested that an overall weight of evidence (WoE) approach,which can also consider the unique properties of the substance, be applied. While CPY and its transformation productsare not currently being evaluated as POPs under the SC, CPY is widely used globally and some have suggested that itsproperties should be evaluated in the context of the SC, especially in locations remote from application. In Europe, allpesticides are being evaluated for properties that contribute to persistence, bioaccumulation, and toxicity under the aegisof EC Regulation No. 1107/2009: ‘Concerning the Placing of Plant Protection Products on the Market.’ The properties thatcontribute to the P, LRT, B, and T of CPY were reviewed, and a WoE approach that included an evaluation of the strengthof the evidence and the relevance of the data to the classification of CPY and CPYO as POPs or PBTs was applied. Whiletoxic under the simple classification system used in EC Regulation No. 1107/2009, based on its intensive properties andresults of monitoring and simulation modeling, it was concluded that there is no justification for classifying CPY or itsmetabolite, CPYO, as a POP or PBT.

Keywords: Stockholm Convention; EC Regulation No. 1107/2009; Chlorpyrifos oxon; Long-range transport

BackgroundA number of chemicals, including several organochlorinepesticides, have been identified as persistent organicpollutants (POPs). The POPs were first brought to theattention of the general public by Rachel Carson in herbook Silent Spring [1]. In that now famous book, shepointed out that a number of chemicals, including the

* Correspondence: [email protected] for Toxicology, School of Environmental Sciences, University ofGuelph, Guelph, ON N1G 2 W1, CanadaFull list of author information is available at the end of the article

© 2014 Giesy et al.; licensee Springer. This is anAttribution License (http://creativecommons.orin any medium, provided the original work is p

pesticide dichlorodiphenyltrichloroethane (DDT) and itstransformation products, dichlorodiphenyldichloroethylene(DDE) and dichlorodiphenyldichloroethane (DDD), werenot only persistent but also biomagnified in food chains,caused adverse effects in non-target organisms, such asbirds, and underwent long-range transport (LRT) to moreremote and pristine areas, such as the Arctic and Antarctic.At about the same time, it was recognized that a number ofother organochlorine pesticides and the industrial chemicalpolychlorinated biphenyls (PCBs) also had properties con-sistent with them being POPs. Since that time, these and

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additional chemicals have been identified as POPs and themanufacture and use of these substances are regulated at theglobal level by the Stockholm Convention (SC) [2] and theUN-ECE POP Protocol [3]. While many of the chemicalsclassified as POPs have been organochlorines, some such asthose that contain the terminal degradation product, per-fluorooctanesulfonate (PFOS) are not. As in many regulatorysystems, the SC uses the precautionary approach; however,this includes detailed scientific review by the POPs ReviewCommittee, where there is an opportunity to consider theinherent properties of the chemical under review.While understood in a generic way, the properties that

are used to derive criteria for classification of a chemicalas a POP with LRT, or a PBT, are used differently amongjurisdictions [4,5]. Under the global aegis of the SC, POPsare identified by a combination of intensive properties(independent of concentration), including persistence,biomagnification, and chemical and physical propertiesthat result in harmful interactions with biological systems,and extensive properties (dependent on concentration),including toxicity, hazard, and risk. In addition to the SC[2], several additional frameworks have been developed toassess chemicals based on the properties of persistence,bioaccumulation, and toxicity (P, B, and T). Some of theseframeworks are international, such as the Conventionfor the Protection of the Marine Environment of theNorth-East Atlantic [6]. Others are regional, such as theEU legislation Registration, Evaluation, Authorisation andRestriction of Chemicals (REACH [7]), with a focus on che-micals in commerce, and EC Regulation No. 1107/2009 [8],which is focused on pesticides. National frameworksinclude, for example, the Toxic Substances ManagementPolicy [9], the Toxics Release Inventory Reporting [10], andthe Chemicals Management Plan in Canada [11].Classifying chemicals as POPs or having the properties

of PBTs is used to assist industries in making decisionsabout the development of chemicals and governments inpriority setting and regulation of these chemicals. Theconcepts of persistence, bioaccumulation, and toxicityare commonly used in the scientific literature, as is theinternationally used concept of a POP. PBT, as a term,appears to have originated in policies of the Japanesegovernment in the 1970s, even though the term did notappear in the peer-reviewed scientific literature until the1990s [5]. This term and underlying concepts are beingused increasingly by policy makers in regulatory deci-sions. Unfortunately, inconsistent definitions and criteriafor classifying chemicals as being PBT vary among juris-dictions and have been changing over time. Further-more, this very simplistic method of classification doesnot take into account the unique properties of chemicalsor the environments to which they are released [12].These shortcomings are exacerbated by both poorquality of data and, in some cases, little or a complete

lack of data, such as was the case for perfluoroundecanoicacid [5].There are a number of uncertainties in these approaches

that require interpretation of metrics such as persistence invarious media, bioaccumulation, and toxicity. Since every-thing can be toxic, the critical issue is not the inherenttoxicological properties of a chemical, which is its potency,but the concentration to which it can accumulate intovarious matrices of the environment. Ultimately, interpret-ation of the potential for harm that can be caused by achemical of concern (COC) is duration and intensity ofexposure that determines the severity and rate of damage.Injury occurs when the rate of damage exceeds the rate ofelimination and/or repair. So the concept of toxicity needsto be considered not in abstract or absolute terms, butrelative to exposures. Of the three principal parametersused to classify chemicals, toxicity is the least welldescribed and interpretable. Adverse effects are onlyobservable when the concentration (exposure) of a sub-stance exceeds the threshold for effects for a sufficient dur-ation. Because of its intensive properties, a chemical, suchas the organophosphorus pesticide chlorpyrifos (CPY), canhave relatively great potency to cause adverse effects, but ifthe concentrations in various matrices do not exceedthresholds for adverse effects, there is no adverse effect.Risk is defined as the likelihood for exceedence of a thresh-old (used here in the inclusive sense) and is alwaysexpressed as a probability. This has been known for sometime, as attributed to Antoine Arnauld in a monastic textin 1662: ‘If, therefore, the fear of an evil ought to be pro-portionate, not only to its magnitude, but also to its prob-ability…’ (page 368 in [13]). Several properties drive theprobability of exposure but the most important parameteris persistence. If a COC is sufficiently persistent, then thereis always the potential for accumulation and toxicity. Evenif a compound degrades relatively rapidly, if it is releasedcontinuously or organisms are exposed for a sufficient dur-ation, it might be present in sufficient quantities to exerttoxicity. Such substances have been termed ‘pseudo persist-ent.’ So here the classification of CPY as a POP is consid-ered not only relative to specific, absolute ‘trigger’ valuesfor the classifying parameters but also relative to what islikely to occur in the environment. That is, while it isknown that CPY is inherently hazardous, what is the aggre-gate potential for exposure in various environmentalmatrices [14,15]? Instead of classifying chemicals asPBT based solely on a few simple, numeric criteria, atransparent weight of evidence (WoE [16]) approach,which can also consider the unique properties ofCOCs, should be applied [5,17]. This approach allowsall relevant scientific data to be considered on a case-by-case basis, but the process of classification requiresmore description of the process and expert evaluationof the results of the multiple lines of evidence.


While CPY and its transformation products are not cur-rently being formally evaluated as POPs under the SC, ithas undergone simplified screening as an alternative toendosulfan. This screening suggested that CPY mightmeet all Annex D criteria (be a POP) but there are onlyequivocal or insufficient data [18]. CPY is widely usedglobally and some have suggested that its propertiesshould be evaluated in the context of POPs [19]. InEurope, all pesticides (excluding biocides used to controlbacteria and fungi) are being evaluated for properties thatcontribute to persistence, bioaccumulation, and toxicity(PBT) under the aegis of EC Regulation No. 1107/2009:‘Concerning the Placing of Plant Protection Products onthe Market’ [8]. Under EC Regulation No. 1107/2009,products identified as POPs under the SC are not allowedto be used.Properties that contribute to P, LRT, B, and T of CPY

have recently been reviewed [15,20]. These reports werepart of a series devoted to assessing risks to environmentsassociated with the use of CPY in the United States ofAmerica (USA). This report builds on these previousreports but refines the assessment with a WoE approachthat includes an evaluation of the strength of evidence andrelevance of the data to classification of CPY as a POP orPBT. There is general recognition that industry has aresponsibility to evaluate its commercial products, espe-cially chemicals such as pesticides, for their possible envir-onmental impacts. One approach for doing this is to usePOP and PBT criteria as a basis for quantitative evaluationof properties, even when there is little likelihood that thechemical will be considered or declared to meet thesecriteria. In short, established POPs and PBTs are used as‘benchmarks’ against which the chemical in question can becompared. It is partly in this spirit that this evaluation wasundertaken.Chemicals can be assessed and classified as PBTs under

several auspices with varying sets of guidelines. Whilethere is some guidance on how the classification shouldbe done [21], none of these processes are inherentlyassessments of risk. That is, they do not consider

Table 1 Criteria for categorization of compounds as POPs and


Water: DT501

> 2 monthsBCF or BAF >5,000 or Log KOW >5 No specific

adverse humenvironmen

Sediment:DT50 >6 months

High bioaccumulation in other species, hightoxicity or ecotoxicity

Soil: DT50 >6 months

Otherevidence ofpersistence

Monitoring data in biota indicating that thebioaccumulation potential is sufficient to justifyits consideration within the SC

From [2,3], 1DT50; note that the SC uses the term half-life but does not state whethe

probabilities of exceeding threshold concentrations for de-fined effects in the environment. At best, these processesare an evaluation of measured or predicted parametersthat relate to persistence in various media and the poten-tial to bioconcentrate or biomagnify.Since there were no predefined criteria for identification

of POPs, they have been developed over time by various in-dividuals and/organizations from empirical observations ofa number of chemicals that were observed to be persistent,biomagnified, and transported over long distances. Thus,the chemical, physical, biological, and environmental prop-erties of the so-called ‘dirty dozen’ [22,23] were used as thebasis for the trigger values for persistence (P), bioaccumula-tion (B), toxicity (T), and propensity for long-range trans-port (LRT) that are currently used under the SC (Table 1).As has been pointed out elsewhere [17,24], there are noconsistently applied criteria for classification of B other thanthe bioconcentration factor (BCF) in EC Regulation No.1107/2009. Although the bioaccumulation factor (BAF) isalso used in the SC, other criteria for B, such as thebiomagnification factor (BMF) and trophic magnificationfactor (TMF), have not been used explicitly, even thoughthey are better descriptors because they incorporate thepotential for dietary uptake and biotransformation in theaggregate measure of accumulation. Similarly, under theSC, toxicity is simply stated as ‘significant adverse… effects’or ‘high toxicity’ with no indication of what ‘significant’ or‘high’means.Criteria for classification of pesticides or other chemicals

as PBT under EC Regulation No. 1107/2009 or theprogram for REACH, which entered into force on 1 June2007 (Table 2), are similar to those used for POPs (Table 1),but LRT is omitted and the triggers for P and B are morestringent. As has been pointed out elsewhere, criteria usedto classify POPs and PBTs are single values [17] and theclassification process, particularly for pesticides under ECRegulation No. 1107/2009, does not consider additionaldata on intensive properties as well as environmental fateand toxicity that are available for pesticides. Since REACHdoes not have jurisdiction over pesticides, such as CPY,

LRT substances under the SC and UNECE

Potential for long-range transport(LRT)

criteria other than ‘significantan health and/ortal effects’ (in Article 8, 7 (a))

Air: DT50 > 2 days. Monitoring ormodeling data that shows long-rangetransport via air, water, or biota

Concentrations of potential concerndetected in remote locations

r this is is for dissipation or for degradation (transformation).

Table 2 Criteria for the categorization of compounds as PBT under REACH or EC Regulation No. 1107/2009


Marine water: t½ >60 days BCF >2,000 in aquaticspecies

Chronic NOEC <0.01 mg/L or is a carcinogen, mutagen, or toxic for reproduction, or otherevidence of toxicity

Fresh water t½ >40 days

Marine sediment: t½>180 days

Freshwater sediment: t½>120 days

Soil: t½ >120 days

From [7,8].


classification of chemicals in commerce under this legalinstrument is not further discussed, except for purposes ofcomparison.Assessment of chemicals to determine if they should be

classified as POPs under the SC is a lengthy processinvolving nomination of candidate substances by a partyor group of parties, review of data, and final recommenda-tions from a review committee (the POPs RC) [2]. Thisprocess is open, but there is no definitive framework forclassification and criteria are sometimes inconsistentlyapplied [24]. After a COC is classified as a POP, it is addedto Annex A (elimination), B (exemptions), or C (uninten-tional) of the SC. Since, under the SC, the UN does nothave regulatory jurisdiction over the parties (signatory na-tions), ratification of classification and any subsequentphase-out and/or banning of the manufacture and use ofthe POPs are undertaken individually by the parties. In fact,the USA, which is a major player in the manufacture anduse of chemicals, is not a signatory of the SC. Phase-outcan take several years because time is provided for users tofind substitutes and, in some cases, such as DDT, specificexemptions for continued availability may be granted foracceptable purposes such as for the protection of humanhealth.Within the European Union (EU), criteria for assess-

ment of plant protection products (PPPs) for PBT or POPproperties are given in EC Regulation No. 1107/2009 andassessments of individual COCs are conducted by Rappor-teur Member States (RMS) of the EU in much the sameway as registration of new active ingredients. There is noexplicit framework or guidance for classification otherthan a draft document from the EU Directorate Generalfor Health and Consumer Affairs (DG SANCO) [21], and,unlike REACH [7], there is no guidance for how studiesare to be evaluated or how the relevance of the data inthese studies is to be assessed. REACH recommends theuse of a WoE approach for assessing data on chemicals incommerce but does not describe how this is to be done.EC Regulation No. 1107/2009 does not mention WoE atall. Under EC Regulation No. 1107/2009, if a PPP is classi-fied as P, B, and/or T, exceeding trigger values for allthree criteria ultimately results in a ban of the use ofthe product in the EU. Exceeding two of the criteria

results in the PPP being listed for substitution withalternative pesticides that do not exceed establishedtrigger values.Since pesticides are designed to be toxic to at least some

groups of organisms, the criterion for assessment of toxicityis likely to capture all pesticides. Therefore, classification ofPPPs as PBTs under this scheme is primarily driven by theP and B. The trigger for classification as T (Table 2) is‘Chronic NOEC <0.01 mg/L or is a carcinogen, mutagen,or toxic for reproduction, or other evidence of toxicity.’The NOEC trigger is strictly for aquatic organisms, whichwill bias classification of insecticides as T because they areusually equally or more toxic to crustaceans than they areto insects. Few PPPs are deliberately applied to water, sofate and movement in the environment are importantdrivers of concentrations in water, yet these factors are notconsidered in classification. Finally, there is no consider-ation of toxicity for terrestrial species, despite the fact thatit is to this environmental compartment that most pesti-cides are routinely applied.

Problem formulationRegistration and re-registration of pesticides in most juris-dictions require a large number of expensive and demand-ing studies under both laboratory and field conditions onfates and effects of pesticides in the environment as awhole. As illustrated in Figure 1, assessments of risk usedduring registration of pesticides are focused on protectionof non-target organisms that enter and use the treated areasas habitat or that might be affected if the pesticide movesoff the target agroecosystem. The assessment of riskconducted during registration includes characterization ofbioaccumulation and metabolism in key species andtoxicity to a range of species. In the process of decision-making, toxic potency to non-target organisms is consideredand combined with exposures inside and outside of theagroecosystem to assess the acceptability of risks from theuse of the pesticide.Risk, which is the relationship between toxicity and ex-

posure, is not considered in the probabilistic sense in theclassification of chemicals as POPs. The review processunder the SC is designed to ‘evaluate whether a chemicalis likely, as a result of its long-range environmental

Figure 1 Illustration of the basis for risk assessment of pesticides.


transport, to lead to significant adverse human health and/or environmental effects, such that global action iswarranted’ [Annex E in 2], whereby the process is based ona deterministic hazard quotient (Annex E (b)). Under ECRegulation No. 1107/2009, binary criteria are used tocategorize substances by comparing the properties of thecompound to simple threshold or trigger values. Thissimplistic approach is appropriate for lower tier screeningor priority setting, but it is not appropriate as a final step indecision-making.Goals for protection, sometimes referred to as ‘assessment

endpoints,’ are usually either identified explicitly or implicitlyin regulations. In terms of humans and the environment, thegoals of EC Regulation No. 1107/2009 are ‘…to ensure a highlevel of protection of both human and animal health and theenvironment and at the same time to safeguard the competi-tiveness of Community agriculture.’ [8]. In the absence ofmore specific goals, it is logically assumed that the concernis for the general environment, not for a particular local sce-nario. For classification of COCs as POPs under the SC, thisis a global concern. POPs identified under the SC are notpermitted for use in the EU, so the environment of concernunder EC Regulation No. 1107/2009 is that within the EU,which is the jurisdiction of regulation. With this in mind,characterization of P for the regional as well as the global en-vironment was accomplished by refinement of the general-ized assessment presented previously [15].

Properties of chlorpyrifosThe physical and chemical properties of CPY have beensummarized relative to assessment of risk to the

environment of the use of this product in agriculture in theUSA [15,20,25] and are thus not repeated here. The focusof the following sections is on characterizing the P, B, andT properties of CPY in relation to criteria for classificationunder the SC and EC Regulation No. 1107/2009. SinceAnnex II 3.3 of EC Regulation No. 1107/2009 specificallyincludes metabolites, they were included in the assessment.Under environmental conditions, several transformation

products of CPY are formed [20] and have been consideredin the assessment of risks [26]. CPYO is assessed in thisdocument, but trichloropyridinol (TCPy) has not beenidentified as a metabolite of toxicological or environmentalconcern [26,27] and was excluded from consideration here.Because of similarities in the structure of TCPy to

trichlorophenol, from which dioxins and furans are knownto be formed, the possibility of this occurring with CPYwas considered. Dibenzo dioxins and furans were notdetected (limit of detection (LOD) 0.006 to 0.0008 ng/g)in formulations of CPY [28]. A recent study reported theformation of 2,3,7,8-tetrachloro-1,4-dioxino-[2,3-b:5,6-bʹ]dipyridine (TCDD-Py), an analog of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), when pure (2 mg) CPY waspyrolyzed in sealed ampules at 380°C, but not 300°C or340°C, for 15 min in the presence of 10 mL of air [29].Greater amounts of TCDD-Py (≈100-fold) were formedfrom pure TCP under all of the above conditions. TCDD-Py is unstable under the conditions of synthesis of CPYfrom TCP [30], suggesting that, even if it is formed, it willnot become a contaminant in the commercial product. In astudy of effects of combustion on the fate of TCP, only TCPand CO2 were identified in smoke from cigarettes containing


residues (900 ng/cigarette) of 14C-labeled TCP. Detectionlimits for hexane-extractable non-polar compounds (2% oftotal radioactivity applied) such as TCDD-Py were notprovided [31].Dibenzo-p-dioxins have been observed in formulations

of chlorinated pesticides, such as 2,4-D, exposed tosunlight [32]. A study of photodegradation of 14C ring-labeled CPY in buffered and natural waters treated with0.5 and 1 mg CPY/L did not reveal the presence of polarcompounds except CPY and dichloropyridinyl phosphoro-thioate esters and 96% of the degradates formed werepolar compounds [33]. Dioxins such as TCDD are rapidlyphotolyzed by sunlight in the presence of a hydrogendonor with a half-life of the order of hours [34]. Thus, ifTCDD-Py was formed in sunlight, it might be expected tobe photolabile and non-persistent in the environment.A search of the literature failed to reveal the isolation

and identification of TCDD-Py in the environment, eitherbecause it is not formed in detectable amounts, because itis rapidly degraded, or because it has not been analyzedfor. The only papers that reported on its formation and/orbiological activity [29,35] did not conduct analyses ofenvironmental samples. They also did not test whetherTCDD-Py was formed by photolysis from CPY or TCP.TCDD-Py is only moderately toxic to rats. It has an oral

median lethal dosage (LD50) of 300 mg/kg body mass(bm) in rats (strain unspecified), about four orders of mag-nitude less toxic than TCDD, which has an LD50 of 0.022to 0.045 mg/kg bm [36]. Tests in female Sprague–Dawleyrats exhibited loss of body mass but no lethality or grosspathological findings at an even greater acute oral dose of600 mg/kg bm [37]. The same study reported no evidenceof chloracne on the ears of NZ white rabbits treated 18times with a solution containing 50 mg TCDD-Py/L [37].On the basis of this evidence, we conclude that TCDD-

Py is either not formed from CPY or TCP under normalconditions of use or the amounts formed are so small thatit has escaped notice in the analyses of bioaccumulativesubstances in environmental samples. In addition, the rela-tively low toxicity of TCDD-Py indicates that, even ifformed in the environment, it presents little risk to humansor the environment. Thus, TCDD-Py was not included inthe following assessment.

Analysis planSince there was little guidance in categorizing POPs andPBTs [with the exception of 21], WoE was used to selectthe most appropriate data for inclusion in the assessment.WoE is a phrase that is widely misused in the literature[16] and has been applied to a number of procedures forassessment of risk. Here, WoE is used as a quantitativeprocedure for evaluating the strength of studies, based onhow they were conducted, and the relevance of the datafrom the studies to characterization of the COC, CPY, as a

POP or PBT chemical. Strength of studies was evaluatedby a numerical scoring system (see the ‘Quality assurance’section). Relevance was also assessed, particularly in thecase of persistence, where studies were conducted at verylarge rates of application, such as for control of termites,which are inconsistent with current uses, and in the caseof bioconcentration, where studies were conducted atexposures greater than the maximum solubility of theCPY in water. All of the available data were evaluated (seeAdditional file 1), and then, on the basis of strengths ofthe studies, those studies that provided the most robustdata were selected for inclusion in the assessment of thePBT properties of CPY. Studies conducted under non-relevant conditions were then excluded to provide themost robust and relevant data for the characterization.This procedure is different from the assessment con-ducted by Mackay et al. [15] where all data were used,regardless of their strength or relevance.Because extreme (worst-case) values observed in specific

conditions are not representative of all situations, meanvalues were used for comparison to the criteria for classifi-cation, a process which has been recommended in the lit-erature [17] and the draft guidance of SANCO [21].Because most of the processes related to P or B at environ-mentally relevant concentrations are driven by first-orderor pseudo-first-order kinetics and thus are lognormallydistributed, geometric mean values are the most appropri-ate for comparing triggers for classification and were usedin this assessment.Since persistence of CPY in the environment is

dependent on its unique properties as well as the proper-ties of and conditions in the surrounding environment, inthe context of global persistence, all acceptable values forassessment of CPY as a POP were combined [15]. Becauseof the regional focus of EC Regulation No. 1107/2009,data for persistence were segregated into studies from theEU and from other regions. These data were analyzedseparately.In addition to consideration of characteristics related to P,

B, and T, other lines of evidence were also used as a meansof corroboration of the more simple criteria for classifica-tion. As in the SC, one line of evidence was based on re-ports of bioaccumulation of CPY in organisms in the field.Concentrations in aquatic systems in the USA have beenthoroughly reviewed [25] and were not included in the as-sessment presented here other than in the context of asses-sing exceedences of criteria for toxicity and their rapidresponse to changes in pattern of use.

Sources of dataAn exhaustive review of the literature was conducted insupport of an ecological risk assessment of CPY [14, etseq.], and results were compiled into an electronic database,which formed the basis for the information used in this


report. The extensive search of the available literature wasconducted by using Web of Knowledge®, a database withaccess to a number of other digital collections and data-bases. In addition, searches were conducted with GoogleScholar using keyword string searches to access otheravailable peer-reviewed resources. Recent reviews of theliterature on the properties of CPY [15,20] provided anoverview of pertinent studies. Also included in thereviewed body of work were relevant unpublished studiesfrom Dow AgroSciences and its affiliates, which wereprovided to the authors in their original forms.From the results of the extensive literature search, those

studies judged to be directly related to persistence and/orbioaccumulation of CPY were retained for further assess-ment. These included studies on persistence in sediment,soil, and water, performed under laboratory or field condi-tions, and studies from any international jurisdiction. Intotal, 41 papers or reports on bioaccumulation of CPY inbiota and 90 papers or reports on persistence of CPY insoil, sediment, and/or water were included in the scoringevaluation. Data on toxicity to aquatic organisms werepreviously screened for quality [38] and were used in thisassessment without further characterization.

Quality assuranceThose papers retained from the literature search were sub-jected to a WoE assessment with the aim of identifying thosestudies that should form the basis of the final report. Scoringused in our evaluation was based on criteria developed forinclusion of data in the International Uniform ChemicalInformation Database (IUCLID) [39] and more currentupdates. The system was augmented by application ofnumerical scores as has been done previously for selectionof toxicity data for CPY [38]. Specific scoring criteria weredeveloped for each type of exposure, including bio-accumulation in sediment-dwelling organisms, aqueousbioconcentration, bioaccumulation from dietary exposure,persistence in soil, persistence in sediment, and persist-ence in water. These criteria were based on OECDmethods for testing [40] under the relevant conditions(OECD Methods 305, 308, 309, and 315). Criteria assessedthe strength of the methods used in each study, and ascore of 0, 1, or 3 was assigned for each criterion, indicat-ing that the criterion was not met, was attempted but notfully met, or was fully achieved, respectively. The scoringmatrices are provided (see Additional file 1: Table S1).A consensus score was also available as part of the

strength of methods as a mechanism to adjust scores forthose few studies where an invalidating error was notcaptured by the standard matrix for evaluation. Inaddition to assessing the strength of methods, the rele-vance of the study was also assessed by setting limits forrates of application that would be considered environmen-tally relevant (based upon current recommended use rates

[20]) and assigning a score of 0, 1, or 3 for relevance. Afull score was assigned if the rate of application wasequal to or less than the relevant rates of 200 μg/L (accumu-lation in water), 1,000 μg/L (persistence in water), or 8 mg/kg (accumulation or persistence in soil/sediment), a score of1 was assigned if the rate was within 25% of the set value(i.e., ≤250 μg/L, 1,250 μg/L, or 10 mg/kg), and a score of 0was assigned if the rate was more than 25% above the setvalue for environmental relevance. Criteria for relevancealso evaluated whether a description of variance was pro-vided, whether dietary spiking was performed at appropri-ate concentrations (residues not exceeding 5 μmol/g) and/or whether BAF was calculated kinetically from the depura-tion rate constant, as appropriate for each type of study.Briefly, the process of evaluation proceeded as follows: a

study that had been identified through review of the litera-ture and screening process was scored according to the ap-propriate matrix. Scores were recorded, along with adescription of the study methods, and a summary of thereasons for the assigned score for each criterion. Where aspecific study element or criterion was not explicitlyaddressed in the paper and could not be readily inferredfrom the results, it was assumed that the criterion was notmet and a reduced score was assigned. If a missing elementmade the assessment impossible or if it was not possible toscore a particular criterion for an individual study, that cri-terion was omitted from the scoring. This most commonlyoccurred for the use of a solvent in studies of bioaccumula-tion, where a solvent was not required, but in the casewhere it was used, it should be one from an approved list.In cases where no solvent was used, that criterion wasomitted from the assessment.In total, assessments were completed for 44 bioaccumu-

lation studies and 90 persistence studies, and the scoresare summarized in Additional file 1: Tables S2 through 5.It was not possible to obtain a copy of one report on bio-accumulation and two papers on persistence that hadbeen identified during the review of the literature, so thesestudies could not be assessed. After assessment, thosestudies that received scores of less than 50% for strengthof methods were excluded for the purposes of this assess-ment. In total, 23 studies of bioaccumulation of CPY and44 studies of persistence of CPY were included in the finalassessment.

Main textPersistencePersistence was assessed by determining the half-livesfor degradation in soils, sediments, and surface waters.Information from both laboratory and field studies wasconsidered. In the case of field studies, some losses mighthave occurred via volatilization; however, this is a realisticloss process affecting exposure in the field. Thus, thesedissipation data are appropriate for inclusion in the


assessment as long as the degradation in the compartmentinto which partitioning occurs, in this case air, is consideredas well. Studies conducted in the laboratory at normalranges of temperature (15°C to 35°C) were included in theassessment because these temperatures were representativeof the surface layers of the soil in the regions from whichthe samples were obtained. Since the relatively large KOC

of CPY limits mobility in agricultural soils, surficial tem-peratures are more representative of the environment inwhich CPY would be expected to occur. Data from fieldstudies were assumed to have been conducted at realistictemperatures.Use of a half-life implies first-order kinetics, but most en-

vironmental degradation processes are of second order inthe concentration of the chemical and the concentration ofthe reactant, either a chemical or the number of microor-ganisms. Concentrations of reactants can vary widely; thus,half-lives are expected to vary considerably, especially infield studies. Use of extreme values for assessment purposescan be highly misleading since they likely reflect unusuallysmall reactant concentrations. The geometric mean wasused in this assessment as a more rigorous approach and isrecommended for assessment of PBT [21].

SoilIn soils, CPY can be degraded by hydrolysis and also micro-bial transformation. Half-lives for dissipation from soils viaall pathways ranged from 1.1 to 1,576 days (see Additionalfile 1: Table S2). There were several outliers that wereexcluded from the assessment because the application rateswere large (i.e., 1,000 mg/kg for control of termites) [41]and were phased out in 2000. Lesser rates of application


(10 and 100 mg/kg) were included in the assessment. Stud-ies of CPY in soils were divided into those conducted underEuropean conditions and those conducted with soils fromother areas of the world. Studies were also stratified bywhether they were conducted under laboratory or fieldconditions.For European soils [42,43] and non-European soils

(Figure 2) [41,44-50] studied under laboratory condi-tions, the geometric means were 73 and 21 days,respectively. These geometric means do not exceed thecriterion for classification as a POP under the SC(180 days) or as persistent under EC Regulation No.1107/2009 (120 days). The geometric mean half-life forall laboratory-based data for soils without exclusion ofstudies was 32 days [15], also less than the criteria forPOPs or PBT.Geometric means of half-lives derived from field studies

in European soils [51-57] and non-European locations[44,58-66] (Figure 3) were 20 and 13 days, respectively.None of the geometric means for dissipation of CPY in soilsunder field conditions exceeded the threshold to be classi-fied as being persistent in soils under the SC or EC Regula-tion No. 1107/2009. The geometric mean half-life for allfield-based data for soils without exclusion of studies was22 days [15], also less than the criteria for POPs or PBT.Given the relatively short half-lives observed in soil,

CPY is very unlikely to accumulate in soils as a result ofrepeated use in agriculture. Thus, treated soils will not actas a reservoir for other matrices such as water. This isconsistent with rapid decreases in concentrations of CPYin surface water after changes in patterns of use (see the‘Measured concentrations in surface waters’ section).

lorpyrifos (CPY) in soils from European and non-European

Figure 3 Half-life values measured under field conditions for chlorpyrifos (CPY) in soils from European and non-European locations.Geometric means are indicated by vertical arrows.


SedimentIn sediments, under laboratory and field conditions, thehalf-life of CPY ranged from 1 to 223 days (see Additionalfile 1: Table S3). The geometric mean of all studies was29 days. When only those studies that scored in the top50% of studies were included, the geometric mean was25 days. When studies conducted with European andnon-European sediments were considered separately(Figure 4), the geometric means were 40 and 19 days,respectively. None of the geometric means exceeded thethreshold for classification of CPY in sediments as being


persistent under EC Regulation No. 1107/2009. Even themaximum values of 200 and 230 days were only slightlygreater than the 180 days necessary to classify CPY asbeing persistent in sediment. The geometric mean half-lifefor all studies (without exclusions) was 38 days [15], whichis also less than the criteria for POPs or PBT (180 and120 days, respectively).

WaterIn water, CPY can be degraded abiotically by aqueoushydrolysis, photolysis, and microbial transformation.

lorpyrifos (CPY) in sediments from European and non-European


The following sections summarize data on persistence inwater.

Decomposition in aquatic systems In water, hydrolysisis one of the primary mechanisms of degradation of CPY.Aqueous hydrolysis of CPY is inversely proportional to pH[67] (see Additional file 1: Figure S1). In aquatic systems at25°C, half-lives of 73, 72, and 16 days were measured atpH 5, 7, and 9, respectively [summarized in 67]. In distilledwater, in the absence of light and microorganisms, the half-life ranged from as little as 0.01 to 210 days, depending onpH [68-70] (see Additional file 1: Table S4D). Data for half-life measured in distilled were not included in the as-sessment as this matrix is not environmentally realistic.At pH >6 to <10, the half-life of CPY ranged from 4.5to 142 days. When the pH was greater than 10, thehalf-life was as short as 0.01 day. In this assessment,hydrolysis in natural water was considered realistic andwas included, regardless of pH.Half-lives of 22 to 51 days have been reported from me-

tabolism studies conducted in aerobic aquatic systems[71,72]. In the presence of natural sunlight, in sterile pH 7phosphate-buffered solution, the half-life was 30 days [33].Thus, dissipation attributable to photolysis was not muchdifferent from that attributable to hydrolysis alone. Intheir simulations of the dynamics of CPY in aquaticsystems, the US EPA [27] used an aqueous hydrolysis half-life of 81 days at pH 7.0. In surface waters measured inthe laboratory, half-lives of CPY ranged from 1.29 to126 days [69,70,73,74] (see Additional file 1: Table S4B).In an analysis of half-lives in water-only studies with

WoE scores greater than 50%, the geometric mean half-lifefor all waters tested in the laboratory was 6 days. Thegeometric mean half-life for all laboratory-based datawithout exclusion of studies was 21 days [15]. When studiesconducted with waters from European locations (Figure 5and Additional file 1: Table S4A) [75,76] and non-Europeanlocations (Figure 5 and Additional file 1: Table S4B)[69,70,73,74] were considered separately, the geometricmeans were 2.2 and 11 days, respectively. There were nofield data from the EU, but the geometric mean of field datafrom non-EU locations [77,78] was 6 days (see Additionalfile 1: Table S4C). None of these geometric mean valuesexceeds the criterion for persistence (60 days) in water forclassification as a POP under the SC or as persistent(40 days) under EC Regulation No. 1107/2009.

Overall evaluation of persistenceThe geometric means of half-lives of CPY in soils, sedi-ments, and surface waters were less than the thresholds forclassification of a compound as being persistent in soils,sediments, and water under the SC or EC Regulation No.1107/2009. These conclusions are the same as those

reached in an assessment of all the data on persistence inthe earlier assessment by Mackay et al. [15].No studies on persistence CPYO have been reported in

the literature, and it has not been detected as a metabolitein studies on dissipation of CPY in soils [15]. This, alongwith its short half-life in water (4.7 days at pH 7), supportsthe conclusion of Mackay et al. [15] that CPYO is less per-sistent than the parent compound, CPY, and thereforedoes not trigger the criterion for persistence under the SCand EC Regulation No. 1107/2009.

BioaccumulationThe major focus of assessing bioaccumulation under theSC (POPs) and EC Regulation No. 1107/2009 (PBT) is onconcentration from the matrix into the organism as aBCF. Data for BCF (and BAF and biota-sediment accumu-lation factor (BSAF)) from the literature were selectedbased on the quality of the study and relevance of theexposure concentration (see Additional file 1: Table S5).These data are a subset of a larger data set from Mackayet al. [15]. BCF data for fish were separated from otheraquatic organisms. For an amphibian, invertebrates, andplants, BCF, BAF, and BSAF were taken as equivalent forthe purposes of analysis and values are presented graphic-ally (Figure 6). As for toxicity values (below), all data werecombined in the analysis.Empirical values for BCFs for fish ranged from 0.6 to

5,100 [79-94] (see Additional file 1: Table S5A). Fromthe distribution, the smallest value was clearly an outlierand was omitted from the calculation of the geometricmean and the regression. The geometric mean value forBCF for fish was 853, less than the criterion for ECRegulation No. 1107/2009 (2,000) and the SC (5,000).BCFs are often estimated from the octanol-water parti-

tion coefficient (KOW), especially when there is a lack ofempirical data. In the case of CPY, KOW is approximately100,000 [15]. Thus, a fish containing 5% lipid would beexpected to have a BCF of approximately 5,000, which is atthe extreme of empirical observations. This suggests thatCPY is subject to loss processes from fish in addition torespiratory loss, the obvious process being metabolic bio-transformation, but growth dilution and egestion may alsoapply.The BCF (and BAF and BSAF) for invertebrates and

plants (see Additional file 1: Table S5B) ranged from 3.4 to5,700, with a geometric mean of 204. For plants, the great-est value was reported for duckweed (Lemna minor, 5,700)with water lettuce (Pistia stratiotes, 3,000), the third largestand both greater than algae (Oedogonium cardiacuin, 72).The larger values for the two macrophytes might be morereflective of adsorption to the surface of the plant thanuptake into the plant. The BCF values in the invertebratesranged from 3.4 to 691, both in mollusks. The value for theonly amphibian (Ambystoma mexicanum) in the data set

Figure 5 Half-life values measured under laboratory conditions for chlorpyrifos (CPY) in natural waters from European andnon-European locations. Geometric means are indicated by vertical arrows.


was 3,632, which is in the same range as those reported forfishes. The geometric mean value for invertebrates andplants (204) was less than the criterion for EC RegulationNo. 1107/2009 (2,000) and the SC (5,000).No data on biomagnification of the toxicologically rele-

vant metabolite of CPY, CPYO, were found in the litera-ture. Although CPYO is formed in the atmosphere, it isreactive and has a shorter half-life in water (4.7 days atpH 7) than the parent (geometric mean of 2.2 to 11 days)[15]. Despite extensive sampling of surface waters in areas

Figure 6 Graphical presentation of BCF (BAF and BSAF) values for chlindicated by vertical arrows.

of more intensive use, CPYO has never been detectedabove the LOD [25]. Lack of observed bioconcentration orbiomagnification of CPYO is completely consistent withthe greater reactivity of the molecule and its greater solubil-ity and smaller KOW than CPY [15]. All the evidencesuggests that CPYO does not biomagnify.

Concentrations in aquatic biotaConcentrations of chemicals such as CPY in organismscollected in the field are another line of evidence of

orpyrifos (CPY) in aquatic organisms. Geometric means are


bioconcentration and biomagnification. In an extensivesurvey of chemicals in fish from lakes and reservoirs of theUSA [95], residues of CPY were not detected. The methoddetection limit was 59 μg/kg, and 486 samples from preda-tory fish and 395 samples from bottom-dwelling fish wereanalyzed. Concentrations of CPY in samples of fish fromlakes in Western National Parks of the USA were all <1 μg/kg (wet mass; wet. ms.) [96]. Taken together, this is furtherevidence of lack of significant bioconcentration or biomag-nification of CPY into fishes or biomagnification in theaquatic food chain.

Accumulation in terrestrial organismsApart from the detections in plants in montane areas ofCalifornia discussed in Mackay et al. [15], there arereports of detections of small concentrations in plantsfrom more remote areas such as in the panhandle ofAlaska [96] (2.4 ng/g lipid mass (l. ms.) in needles of coni-fers, see the ‘Measured concentrations near areas of use’section). Chlorpyrifos was detected in lichen (0.073 ±0.23 ng/g l. ms.), mushrooms (0.78 ± 0.82 ng/g l. ms.),green plants (0.24 ± 0.47 ng/g l. ms.), caribou muscle(0.57 ± 0.19 ng/g l. ms.), and wolf liver (<0.10 ng/g l. ms.)in Nunavut [97].

Trophic magnificationA characteristic of POPs is biomagnification or trophictransfer in food chains, and this provides another line ofevidence to assess CPY. Only one study was found on move-ment of CPY in food webs. Several current-use pesticideswere measured in a terrestrial food web in the CanadianArctic [97], and CPY was detected frequently in moss andmushrooms (83% to 86%) but at lesser frequency in lichens,willow, and grass (44% to 50%). Concentrations ranged from0.87 ng/g l. ms. in moss to 0.07 ng/g l. ms. in lichen.Concentrations in caribou muscle and total body burdenprovided BMFs of 7.8 and 5.1 compared to lichen; however,the BMF from caribou to wolf was <0.10 (based on concen-trations <MDL). Trophic magnification factors for thelichen-caribou-wolf food chain were all <1 for muscle, liver,and total body burden. That small concentrations of CPYwere found in the Arctic is indicative of some long-rangetransport, but the lack of BMF between caribou and wolfand TMFs of <1 are indicators of no significant trophicmagnification of CPY in the food chain. These additional

Table 3 Toxicity values for CPY in aquatic organisms

Taxon 5th centile (μg/L) 95% CI (μg/L)

Crustaceans 0.034 0.022 to 0.051

Insects 0.087 0.057 to 0.133

Fish 0.812 0.507 to 1.298

Amphibians Too few species for a SSD, range was 19 to a quest

Plants Too few species for a SSD, range was 138 to 2,000

lines of evidence support the laboratory and microcosmdata, which indicate that CPY does not trigger the criterionfor bioaccumulation under the SC or EC Regulation No.1107/2009.

ToxicityToxicity of CPY to aquatic organisms has been reviewed indetail previously in Giddings et al. [38], to birds in Mooreet al. [98], and to the honeybee in Cutler et al. [99]. Ratherthan repeat this information here, the reader is referred tothese papers and their relevant supplemental information.The following sections summarize the toxicity data anddiscuss this in relation to the classification criteria for POPsand PBTs.

Acute toxicity in aquatic organismsBecause CPY dissipates and degrades rapidly in aquatic en-vironments and is only present for short durations (≤4 days),data on acute toxicity were selected as the most appropriatefor assessment of risks in aquatic systems [38]. There werenumerous published studies on laboratory toxicity tests foraquatic organisms. These data were screened for qualityand a subset of the higher quality and most relevant studieswere used in the assessment [38]. Toxicity values wereanalyzed as distributions (species sensitivity distributions(SSDs)) using SSD Master Version 3.0 software [100] and5th centiles (HC5 concentrations) used to characterize tox-icity of CPY to major taxa (Table 3).These acute toxicity values were not separated by type of

medium (saltwater or freshwater) or origin of the species(tropical, temperate, Palearctic, or Nearctic). Analysis of thelarge amount of toxicity data available for CPY has shownthat there are no significant differences in sensitivitybetween these groups [101]. Thus, these data are appropri-ate for classification in the global context (POPs) and in theregional context (PBT).

Toxicity in aquatic meso- and microcosmsSeveral studies of effects of CPY have been conducted inaquatic meso- and microcosms (cosms) and were reviewedin Giddings et al. [38]. These studies were conducted in vari-ous jurisdictions and climatic zones, including Europe(Netherlands and Mediterranean locations), the US Midwest,Australia, and Thailand. Half of the 16 studies reported no-observed-adverse-effect concentrations (NOAECeco) values

Comments

Based on 23 species with a range of 0.035 to 457 μg CPY/L



ionable value of 5,174 μg CPY/L for three species

μg CPY/L


as ‘less than’ values. For the eight studies in cosms whereNOAECecos were available, all were ≥0.1 μg/L and the geo-metric mean was 0.14 μg/L. The NOAECeco is based on ob-servation of short-term effects in some sensitive organisms,from which there is rapid recovery. For a pesticide, such asCPY, which degrades relatively rapidly in the environment,this is an appropriate measure of a threshold for toxicityunder realistic environmental conditions. Because studies incosms incorporate toxicity of organisms from the region, aswell as processes related to fate that may be influenced bylocal conditions such as climate and hydro-geo-chemistry,there may be regional differences in responses. This was notthe case for CPY; the NOAECeco values were the same re-gardless of location of the study. This not only is consistentwith lack of region-specific toxicity tests but also suggeststhat the fate processes that can influence exposures inaquatic systems are not different between regions. Thus, itwas not necessary to separate the studies in cosms forpurposes of classification of POPs and PBTs.

Toxicity to terrestrial organismsBecause CPY is used as a pesticide to protect crops fromdamage by arthropods, it is obviously toxic to terrestrialstages of insects. This is a benefit of use and is not consid-ered an adverse effect. However, toxicity to valued arthro-pods can be considered an adverse effect and, in the case ofthe honeybee, was characterized in a risk assessment ofCPY [99]. CPY is toxic to the honeybee by direct contact(topical toxicity) with the spray and also via the oral route.The former route of exposure is only relevant when beesare present during or shortly after spraying and is mitigatedby restrictions on the label (see the ‘Reports of toxicityunder current conditions of use’ section below). Topical 24-to 48-h LD50 values for formulated CPY range from 0.024to 0.54 (geometric mean =0.123) μg a.i./bee and 0.059 to0.115 (geometric mean =0.082) μg a.i./bee for the technicalproduct. Oral 24- to 48-h LD50s ranged from 0.114 μg a.i./bee for the technical to 0.11 to 1.1 (geometric mean =0.36)μg a.i./bee for the formulated material [99]. Significanttoxicity to honeybees has only been associated with directexposure during spraying and/or during foraging for nectarand/or pollen in recently treated fields (0 to 3 days postspray). Toxicity has not been reported to be caused by CPYoutside the foraging range of the bees, and residues in

Table 4 Acute and dietary toxicity values for CPYO in birds

Species Observation or feeding time (days)

Bobwhite quail 7 observations

Zebra finch 7 observations

Mallard duck 5 exposure, 8 observations

Bobwhite quail 5 exposure, 8 observations

NA, not applicable.

samples of brood comb have not been casually linked tocolony collapse disorder [102]. There is no evidence tosuggest that small concentrations measured outside theareas of use are toxic to bees or other beneficial insects. Asthe honeybee is found in the EU, North America, and otherparts of the globe, there is no need to consider this speciesdifferently across locations. The conclusions regardingtoxicity to honeybees thus apply to considerations of POPsand PBTs.Toxicity to birds has been characterized previously by

Moore et al. [98]. Because of rapid dissipation of CPY inthe environment and in animals, acute toxicity data wereconsidered most relevant for assessing risks. Acute LD50sranged from 8.55 to 92 (geometric mean =30.5) mg CPY/kg bm in 14 species of birds. Few chronic toxicity data wereavailable, but values for the NOEC and LOEL in themallard duck exposed via diet for 28 days were 3 and18.7 mg CPY/kg bm/day, respectively [98]. Risks of CPY tobirds foraging in treated fields were considered de minimisfor most species, except sensitive species foraging in cropswith large application rates (e.g., citrus). This conclusion wasconsistent with the lack of observed mortality of birds infield studies conducted in North America and the EU. Mam-mals are less sensitive to CPY than birds. Acute LC50 valuesfor laboratory test species ranged from 62 to 2,000 mg CPY/kg bm [103]. Several assessments of risk have concluded thatbirds are more sensitive and more likely to be exposed andare protective of risks from CPY in wild and domesticmammals and that risks to these organisms are de minimis[98,104]. Given de minimis or very small risks fromexposures in areas of use, concentrations of CPY reportedfrom semi- and remote locations present even lesser risks tobirds or mammals.Acute and chronic dietary toxicity values for CPYO have

been measured in birds (Table 4). Although data were few,toxicity values were similar to those for CPY, suggesting,as would be expected from the mechanism of action, thatCPYO has similar toxicity to the parent CPY.

Chronic toxicity in aquatic organismsAlthough there are no known situations where exposuresof aquatic organisms to CPY are long-term, some toxicitytests, such as mesocosm studies, have used repeated expo-sures with no hydraulic flushing to assess the equivalentof repeated exposures. The most sensitive NOEC reported

Toxicity value (mg/kg) 95% CI Reference

LD50 = 8.8 bm 7.2 to 10.7 [105]

LD50≥ 30 bm NA [106]

LC50 = 523 mg/kg diet 363 to 796 [107]

LC50 = 225 mg/kg diet 173 to 292 [108]


for an aquatic organism was from one of these studies:0.005 μg CPY/L for Simocephalus vetulus in a mesocosmexperiment [75]. This value is relevant to assessment ofCPY as a PBT chemical.

Reports of toxicity under current conditions of useThe above conclusions of lack of significant toxicity toaquatic and terrestrial organisms under current conditionsof use in the USA is supported by the very few reports onfish, invertebrate, bee, and bird kills reported in the last12 years [38,98,99]. Where these few incidents haveoccurred, most have been the result of accidents ordeliberate misuse.

Toxicity in relation to classification as a POPThe criterion for toxicity for classification of POPs is‘significant adverse effects’ without a clear definition of‘significant’ or the location of the effects. We have inter-preted that to mean that the use of CPY results in un-acceptable risks in areas outside but not directly adjacentto the area of application (i.e., edge of field). As a pesticide,risks to target organisms in the agricultural field are ac-cepted, but risks to non-target organisms, especially out-side the areas of application, are considered undesirable.None of the data on toxicity of CPY or CPYO to non-

target organisms suggests that there are significant adverseeffects in the environment outside of the areas of use[15,38,98,99]. Even in areas of use, risks to birds and mam-mals are small or de minimis. The data on toxicity of CPYand CPYO to birds, mammals, and aquatic organismsdetermined under laboratory conditions is robust. Thesedata are complemented by studies in aquatic cosms, whichare more representative of exposures in natural environ-ments, showing similar patterns of toxicity and includingspecies that have not been tested in the laboratory underguideline protocols. There are some uncertainties. Not allspecies have been tested and many groups of marinespecies have not been tested at all; however, this is notunique and applies to pesticides other than CPY and tochemicals in general.Considering all of the data on toxicity, we conclude that

CPY and CPYO do not exceed the POPs criterion of‘significant adverse effects’ (Table 1) for toxicity to organ-isms in the environment.

Toxicity in relation to classification as a PBTThe criterion for classification of pesticides as toxic underEC Regulation No. 1107/2009 is ‘Chronic NOEC <0.01 mg/L (10 μg/L) or is a carcinogen, mutagen, or toxic forreproduction, or other evidence of toxicity’ (Table 2). Ashas been discussed before [17], the criterion refers only toaquatic organisms and terrestrial organisms are not consid-ered. The NOEC for S. vetulus (0.005 μg CPY/L) is lessthan the criterion, so CPY would be classified as T. In

addition, the acute toxicity values for CPY for many crusta-ceans and insects, and even some fish, were <10 μg CPY/L[38]. Given that CPY is an insecticide and that crustaceansand insects are the most sensitive taxa [38], this is notunexpected. However, several additional factors that placetoxicity in perspective must be considered. CPY is notapplied directly to water, so exposures in this environmentare indirect and small [25]. Since CPY is not persistent inwater or other environmental compartments, chronictoxicity values are not environmentally realistic or appropri-ate for classification of toxicity. There is robust evidence toshow that CPY is not sufficiently persistent in any environ-mental compartments to justify durations of exposure asso-ciated with chronic toxicity. Thus, it would have beeninappropriate to compare concentrations in remote regionsto those associated with chronic effects of CPY. No chronictoxicity data for CPYO were available; however, it has a rela-tively short half-life in water [15] and has not been detectedin surface waters, even in areas of high use [25].Carcinogenicity, mutagenicity, or reproductive toxicity

of CPY were not assessed in this evaluation, but havebeen assessed in recent reviews by the US EPA as partof the re-registration process. Based on current usepatterns, CPY was not identified as a mutagen, carcinogen,reproductive toxicant, or immunotoxic agent [26]. The verysmall concentrations reported in semi- and remote areasdo not represent a risk to humans through drinking wateror via the food chain.

DiscussionAtmospheric transportThe potential for LRT is considered in both water and air.Since the half-life of CPY in water does not exceed thecriterion for persistence in water (see the ‘Water’ section),it is unlikely that LRT in water would be a significantissue. Thus, the potential for LRT of CPY and CPYO inthe atmosphere was assessed in detail. The criterion forLRT in air under the United Nations Economic Commis-sion for Europe [3] is that the half-life is ≥2 days (Table 1)or that monitoring or modeling data demonstrates long-range transport. Since masses of air containing volatilizedCPY can move, a static determination of the half-life in airis not instructive. The issue is: can CPY persist long enoughto move significant distances from where it is released anddeposit into soils and water at concentrations sufficient tocause adverse effects? Evidence that CPY is subject to LRTis provided in reports of concentrations in air and othermedia at locations remote from sites where CPY is appliedin agriculture [15].The assessment reported by Mackay et al. [15] used a

combination of analyses, including measured concentrationsat locations distant from sources, in conjunction with massbalance modeling. Predictions of atmospheric transport weremade by the use of simple mass balance models such as


TAPL3 and the OECD Tool [15,109,110]. These modelshave been used in regulatory contexts and characterizeLRT as a characteristic travel distance (CTD), which isdefined as the distance that approximately two thirds of theoriginally released mass of CPY or CPYO is transportedfrom the source before it is deposited or transformed.Detailed assessments of the properties of CPY [15,20,111]and its fate in the environment and potential risks [14] havebeen published previously [67,112]. CTDs of several pesti-cides, including CPY, have been estimated [113]. Results ofthese modeling exercises have suggested a CTD of 280 to300 km for CPY if it is assumed that the atmospheric half-life is 12 h, the narrow range being the direct result of closesimilarities between the model equations. As is discussedbelow, this estimate of CTD reflects an unrealistically longatmospheric half-life.

Predicted concentrations in the environmentThe assessment of LRT presented here went beyond de-termination of CTD and the related characteristic traveltime (CTT) and also included consideration of estimatesof concentrations of CPY and CPYO in other environmen-tal media such as rain, snow, and terrestrial phases, as wellas in the atmosphere at more remote locations, includinghigher altitudes [15]. A relatively simple mass balancemodel was developed and used to predict concentrationsin various media at various distances from sources whereCPY was applied in agriculture, which could be comparedto measured concentrations of CPY in air and othermedia. Results of the model can then serve as a semi-quantitative predictive framework that is consistent withobservations.As an example of dissipation of a parcel of air contain-

ing 100 ng CPY/m3, which is typical of concentrations1 km from application sources, a model was developed toassess the concentration as it is conveyed downwind [15].The mass would be decreased as a result of transform-ation processes, primarily reaction with •OH radicals,deposition, and dilution by dispersion. Oxidation resultsin formation of primarily CPYO. By using the TAPL3simulation of a relatively large environmental area and ahalf-life in air of 3.0 h and conservative (longer duration)half-lives in other media and assuming an emission rate toair of 1,000 kg/h, the resulting mass in air is 4,328 kg, theresidence time in air and the CTT is 4.3 h, and the corre-sponding rate constant for total loss is 0.231/h. The CTDof approximately 62 km is the product of 4.3 h and thewind velocity of 14.4 km/h. The rate of transformation is993 kg/h, and the net losses by deposition to water, vege-tation, and soil total about 7 kg CPY/h, which correspondsto a rate constant of 0.0016/h and is less than 1% of therate of degradation. The critical determinant of potentialfor LRT is the rate of transformation from reactions with•OH radicals in air. If the half-life is increased by an

arbitrary factor of 4 to 12 h, as was assumed in [113], theCTD increases to 244 km [15].Results of simulation models predicted concentrations

and partial pressures or fugacities (expressed in units ofnPa) at several distances from application of CPY in typicalagricultural uses. A simple but approximate approach toestimate concentrations of CPY at distances from sources isto use a dispersion model to estimate concentrations atground level from a ground-level source using standard airdispersion parameters [114]. Near the area of application,such as at a distance of 1 km and assuming a 0.1-h air tran-sit time, air concentrations (C1 km) were assigned a value of100 ng CPY/m3 (approximately 700 nPa). Concentrationsof CPY are primarily controlled by rates of evaporation anddispersion rather than reactions with •OH. At a distance of120 km and a transit time of 8.4 h, which is equivalent totwo CTDs, 84% of the volatilized CPY would have beentransformed and the concentration of CPY in air would be0.022 ng CPY/m3 (0.16 nPa). At steady state, rain waterwould have a concentration of 0.1 ng CPY/L and snow aconcentration of 1.5 ng CPY/L. If a very conservative half-life of 12 h for CPY were assumed, the fraction of CPYtransformed would be only 38% and thus greater concen-trations of CPY would persist for longer distances. At a dis-tance of 300 km and a transit time of about 20 h, which isequivalent to approximately five CTDs, 1.0% of the initialmass of CPY would remain because the CPY would havebeen subjected to nearly seven half-lives. Concentrations atthis distance from the source would likely be 0.0003 ngCPY/m3 (0.002 nPa) or less. Concentrations of 0.003 ngCPYO/m3 would be expected. Thus, at this distance fromthe source, CPYO would be the primary product present,at a concentration which is near the typical limit of quanti-tation. Rain, if at equilibrium with air, would be expected tocontain a concentration of 0.001 ng CPY/L and snow0.02 ng CPY/L. Given an assumed half-life of 3 h and thetime to be transported this distance, it is unlikely that,under normal conditions, significant quantities could travelmore than 300 km. Observations of detectable amounts ofCPY at greater distances, such as 1,000 km [115], suggestthat, at least under certain meteorological conditions asmay apply at high latitudes or times of low solar radiationand less production of •OH radicals, the half-life is longerthan was assumed in this analysis. The significant conclu-sion is that partial pressures, fugacities, and concentrationsin air at distances of 100 s of km are expected to be reducedby a factor of a million or more from those within a kmfrom sources.

Measured concentrations near areas of useWhile the vapor pressure of CPY is considered to bemoderate, CPY can be measured in the air during andafter application. In the 12 h following application of theliquid formulation to the surface, approximately 10% to


20% of the applied material volatilizes, but variability isexpected diurnally, with temperature, rainfall, and soil mois-ture content. Sorption then ‘immobilizes’ the CPY and sub-sequent volatilization is slower, with a rate of approximately1% per day that decreases steadily to perhaps 0.1% per dayin the subsequent weeks [15]. Concentrations in air thatexceed 20 ng CPY/m3 have been observed near sources ofapplication in agriculture [15]. Concentrations of CPY in airimmediately above a potato field in the Netherlands at noonin midsummer ranged from 14,550 to 7,930 ng/m3 at 1 and1.9 m above the crop 2 h after application [116]. Thesedecreased to a range of 2,950 to 1.84 ng/m3 after 8 h and to26 to 15 ng/m3 in the 6 days following application. Concen-trations of CPY in air following an application of 4.5 kg/hato turf were in the range of 1,000 to 20,000 ng/m3 [117].This might be a ‘worst case’ in terms of concentrations andrepresents approximately 10% of the saturation concentra-tion in air, i.e., the vapor pressure/RT, where RT is the gasconstant-absolute temperature group. Concentrations ofapproximately 100 ng CPY/m3 are regarded as typical ofareas immediately downwind (approximately 1 km) of ap-plication sites [15].

Measured concentrations and deposition in semi-remotelocationsChlorpyrifos and CPYO have been detected in the envir-onment [15]. Concentrations in the range of 0.01 to 10 ngCPY/m3 that have been reported at distances of up to100 km from sources are considered to be regional.Concentrations less than 0.01 ng CPY/m3 have beenobserved in more remote areas. Approximately 70% of thedata for concentrations in air were in the range of 0.01 to1.0 ng CPY/m3. For rain, the greatest frequency (40%) wasin the range 1 to 10 ng CPY/L. Concentrations of CPY insnow exhibited similar patterns, but with more concentra-tions in the range 0.01 to 0.1 ng CPY/L [15].Apart from the detections in plants in montane areas of

California discussed in Mackay et al. [15], there are reportsof detections of small concentrations from more remoteareas, such as the panhandle of Alaska [96]. Concentrationsof CPY in lichen were <MDL (1 ng/g l. ms.) and mean con-centrations as great as 2.4 ng/g l. ms. in needles of conifersin Denali National Park, Wrangell-St. Elias National Parkand Preserve, Glacier Bay National Park, Katmai NationalPark and Preserve, the Stikine-LeConte Wilderness, and theTongass National Forest in samples collected between 2002and 2007. The amounts of CPY measured were small incomparison to those reported at locations closer to regionsof release [15] and are not suggestive of the transport oftoxicologically significant amounts of CPY. It is thus not sur-prising that small but detectable concentrations can befound in remote locations such as Svalbard [113,115]. Thelargest concentration in a remote location was found in icecorresponding to the 1980s from Svalbard. While that

concentration was 16 ng CPY/L, concentrations measuredmore recently are generally <1 ng CPY/L. Residues ofCPY and CPYO were absent in the surface section of thecore, representing 1990 to 1998 [115], despite this likelybeing the period of greatest global use. A survey ofconcentrations of CPY in a north–south transect of lakesin Canada reported the presence of residues of CPY [113].Greater concentrations were reported in lakes with agri-cultural inputs (mean =0.00065 μg/L). Concentrations andfrequency of detection decreased with increasing latitude,with mean concentrations of 0.00082, <0.00002, and0.00027 μg/L for remote mid-latitude, subarctic, and arcticlakes, respectively. These were grab samples and the tem-poral profile of exposures are not known; however, allconcentrations are several orders of magnitude less thanthe HC5 for crustaceans (0.034 μg/L, Table 3) or theNOAECeco of ≥0.1 μg/L (see the ‘Toxicity in aquaticmeso- and microcosms’ section) for repeated exposures inmicrocosms.

Measured concentrations in surface watersChlorpyrifos (but not its toxicologically significant productof transformation, CPYO) has been detected in surfacewaters, particularly in areas of intensive use [25]. Inseveral regions of the USA, these concentrations havedecreased since the late 1990s and early 2000s [118-120],most probably as a result of changes in patterns of use[25]. Thus, rather than an upward trend in concentrations,the frequency of detection and the concentrations mea-sured in surface waters have declined. This is not indica-tive of persistence in the environment.

ConclusionsWhile both CPY and CPYO are classified as “toxic”, basedon the assessment of persistence and bioaccumulation, allthe lines of evidence suggest that neither would be classi-fied as persistent or bioaccumulative under the SC or ECRegulation No. 1107/2009. Based on the analysis of LRT,neither CPY nor its most toxic transformation product,CPYO, would be transported at sufficiently great concen-trations to cause adverse effects in humans or the environ-ment in remote areas. Based on the simple criterion fortoxicity in EC Regulation No. 1107/2009, CPY (and byextension, CPYO) would be classified as toxic; however,when a more refined assessment of ‘risk’ is consideredinstead of ‘hazard,’ it does not present unacceptable risks tohumans or organisms in the environment. Based on thewording of the SC, CPY and CPYO do not present a signifi-cant adverse risk to humans and the environment. Theseconclusions are based on the selection of higher qualitydata but are similar to those reached by inclusion of all thedata [15].


Additional file

Additional file 1: Supplemental information for Giesy et al. 2014[14]. The additional file provides one figure and several tables of rawdata related to the criteria for WoE, persistence, and bioaccumulation.

AbbreviationsB: bioaccumulative; BAF: bioaccumulation factor; BCF: bioconcentrationfactor; bm: body mass; BMF: biomagnification factor; BSAF: biota-sedimentaccumulation factor; COC: chemical of concern (substance of concern);CPY: chlorpyrifos; CPYO: chlorpyrifos oxon; CTD: characteristic travel distance;CTT: characteristic travel time; KOC: water-soil partition coefficient correctedfor the amount of organic carbon in the soil; KOW: octanol-water partitioncoefficient; l. ms.: lipid mass; LC50: lethal concentration for 50% of testindividuals; LRT: long-range transport; NOEC: no-observed-effect concentration;nPa: nanoPascals; P: persistent; PBT: persistent, bioaccumulative, and toxic;POP: persistent organic pollutant; REACH: Registration, Evaluation, Authorisationand Restriction of Chemicals; SC: Stockholm Convention; T: toxic; t½: half-life;TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD-Py: 2,3,7,8-tetrachloro-1,4-dioxino-[2,3-b:5,6-b′] dipyridine; TCP: trichlorophenol; TCPy: trichloropyridinol;TMF: trophic magnification factor; UNEP: United Nations EnvironmentProgramme.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsThe authors JPG, KRS, and DM contributed directly to the concepts, analyses,development of conclusions, and writing of the paper. JA provided technicalassistance and assessment of the strength and relevance of the studies, andKRS formatted and prepared the paper for submission. All authors read andapproved the final manuscript.

AcknowledgementsFunding for this assessment was provided by Dow AgroSciences, LLP, USA.The opinions expressed in this paper are those of the authors alone. All ofthe references are available from publishers or from the authors except forthose reports which are considered to contain confidential businessinformation. These reports have been provided to the appropriate regulatoryagencies for use in their reviews and deliberations relative to chlorpyrifos. Ifreaders wish to obtain specific information contained in these reports,requests will be passed on to the registrant on a case-by-case basis. JPG wassupported by the Canada Research Chairs Program, a Visiting DistinguishedProfessorship in the Department of Biology and Chemistry and State KeyLaboratory in Marine Pollution, City University of Hong Kong, the 2012 ‘HighLevel Foreign Experts’ (#GDW20123200120) program, funded by the StateAdministration of Foreign Experts Affairs, the P.R. China to Nanjing University,and the Einstein Professor Program of the Chinese Academy of Sciences.

Author details1Department of Veterinary Biomedical Sciences and Toxicology Centre,University of Saskatchewan, Saskatoon, SK S7B 5B3, Canada. 2Centre forToxicology, School of Environmental Sciences, University of Guelph, Guelph,ON N1G 2 W1, Canada. 3Centre for Environmental Modelling and Chemistry,Trent University, Peterborough, ON K9J 7B8, Canada. 4Stantec, 603-386Broadway Ave, Winnipeg, MB R3C 3R6, Canada.

Received: 3 January 2014 Accepted: 6 October 2014

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doi:10.1186/s12302-014-0029-yCite this article as: Giesy et al.: Evaluation of evidence that theorganophosphorus insecticide chlorpyrifos is a potential persistent organicpollutant (POP) or persistent, bioaccumulative, and toxic (PBT). EnvironmentalSciences Europe 2014 26:29.

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Supplemental Information for Giesy et al. Environ. Sci. Europe 2014

Figure S1. Relationship between half-life of chlorpyrifos in distilled water and pH

pH1 10

Hal

f-life

(d)

0.001

0.01

0.1

1

10

100

1000

Omitted from regression


Table S1A: Evaluation matrix for strength and relevance of BSAF studies based on OECD Method 315 [1]. Bioaccumulation in Sediment-Dwelling Organisms - Strength Yes

3 pts Attempted

1 pt No

0 pts OECD Guideline

a) 28 d uptake phase plus max 10 d depuration phase (unless otherwise justified)

b) 96 h toxicity tests conducted between definitive tests on culture to ensure health

c) Similarly sized animals from the same stage used for testing

d) Maximum storage time of 8 weeks for sediments prior to testing

e) At least 3 replicates per treatment per sampling event

f) Sampling of water quality regularly throughout the assay

g) Sampling of sediment and animals at least 6 times during uptake and elimination phases

h) Cumulative mortality not to exceed 20% (treatments + controls)

i) Exposures confirmed by measurement

j) Metabolites measured in matrix and test organism

Total Strength Score

Consensus Strength Score Bioaccumulation in Sediment-Dwelling Organisms - Relevance Yes

3 pts Attempted

1 pt No

0 pts a) Description of variance provided

b) BAF calculated kinetically from depuration rate constant

c) Realistic exposure concentrations used (< 200 μg/L)

Total Relevance Score


Table S1B: Evaluation matrix for strength and relevance of BCF studies based on OECD Method 305 [2]. Aqueous Exposure Bioconcentration Test - Strength Yes

3 pts Attempted

1 pt No


a) 28 d uptake phase plus depuration phase (~ half length of uptake, 95% reduction, unless otherwise justified)

b) Mortality of fish less than 5% over a 7 d acclimation period prior to testing

c) Appropriate test conditions: less than 2°C change in temperature over entire study period; DO not less than 60% saturation; pH between 6 and 8.5 to begin and not to vary by more than 0.5 pH units; 12-16 h light period

d) Use of allowable solvents (if applicable): ethanol, methanol, dimethyl formamide, or triethylene glycol; not to exceed 100 mg/L

e) At least 4 fish per treatment per sampling event

f) All fish from same year class and similar weight at test initiation; loading rate between 0.1 and 1.0 g weight wt/L/day

g) Sampling of water quality regularly throughout the assay

h) Sampling of animals at least 5 times during uptake phase and 4 times during elimination phase

i) Cumulative mortality not to exceed 10% (treatments + controls) (or 30% overall if test duration extended)

j) Exposures confirmed by measurement

k) Metabolites measured in matrix and test organism


Consensus Strength Score

Aqueous Exposure Bioconcentration Test - Relevance Yes

3 pts Attempted

1 pt No


b) Realistic exposure concentrations used (< 200 μg/L)



Table S1C: Evaluation matrix for BMF studies based on OECD Method 305 [2]. Dietary Exposure Bioaccumulation Test - Strength Yes

3 pts Attempted

1 pt No


a) 7-14 d feeding (uptake) phase plus up to 28 d depuration phase

b) Mortality of fish less than 5% over a 7 d acclimation period prior to testing

c) Appropriate test conditions: less than 2°C change in temperature over entire study period; DO not less than 60% saturation; pH between 6 and 8.5 to begin and not to vary by more than 0.5 pH units; 12-16 h light period

d) Use of commercial fish food with homogeneity of test substance in spiked food (within 15%)

e) Food samples analyzed at least in triplicate at the beginning and end of uptake for lipid content and test substance; undetectable or trace levels of test substance in controls

f) 5-10 fish per treatment per sampling event; measured for weight and length at each time point

g) All fish from same year class and similar weight at test initiation; loading rate between 0.1 and 1.0 g weight wt/L/day

h) Sampling of water quality regularly throughout the assay

i) Sampling of animals at least at the end of the uptake phase and 4-6 times during elimination phase

j) Cumulative mortality not to exceed 10% (treatments + controls) (or 30% overall if test duration extended)

k) Metabolites measured in matrix and test organism



Dietary Exposure Bioaccumulation Test - Relevance Yes

3 pts Attempted

1 pt No



b) Diet spiked between 1-1000 µg/g with tissue residues not exceeding 5 µmol/g


Table S1D: Evaluation matrix for strength and relevance of sediment persistence studies based on OECD Method 308 [3]. Persistence in Sediment - Strength Yes

3 pts Attempted

1 pt No


a) Use of labeled material

b) 90-110% recovery for labeled material, 70-110% recovery for un-labeled c) Information on water (origin/source, temperature, pH, TOC, DO) and sediment (origin/source, depth of layer, pH, particle size distribution, TOC, microbial biomass, redox potential) provided

d) Tested in the dark at constant temperature between 10 and 30°C (typically 20 ± 2°C)

e) Two or more test vessels sampled at each sampling time f) Duration not exceeding 100 d but continuing until degradation and distribution patterns are established or 90% of test substance has been removed by transformation/volatilization

g) At least 50 g of sediment (dry wt) per test vessel h) LOD of at least 0.01 mg/kg in water or sediment or 1% of initial amount applied (whichever is lower)

i) Soil in controls tested for microbiological activity and beginning and end of study.


Consensus Strength Score Persistence in Sediment – Relevance Yes

3 pts Attempted

1 pt No

0 pts a) Realistic rate of application (<8 mg/kg)



Table S1E: Evaluation matrix for strength and relevance of soil persistence studies based on OECD Method 307 [4]. Persistence in Soil - Strength Yes

3 pts Attempted

1 pt No


a) Labeled or non-labeled soil for rate of transformation studies; labeled required for pathway studies (at least 95% pure test substances)

b) 90-110% recovery for labeled soil, 70-110% for non-labeled

c) Tested in dark at constant temperature of 20 ± 2°C (for temperate climates) or 10 ± 2°C (for colder climates)

d) Rate and pathway tests not exceeding 120 d; longer incubation periods (up to 6 or 12 months) can be used but require justification

e) Duplicate sampling at each time point

f) Information provided re: test soils – details of collection site, procedure of sampling, properties (pH, OC, microbial biomass, exchange capacity, bulk density, water retention, texture), length and conditions of storage

g) LOD of at least 0.01 mg/kg in water or sediment or 1% of initial amount applied (whichever is lower)

h) Use of sandy loam/silty loam/loam/loamy sand with pH 5.5-8.0, OC between 0.5 and 2.5%, and microbial biomass of >1% TOC



Persistence in Soil - Relevance Yes

3 pts Attempted

1 pt No

0 pts a) Realistic rate of application (<8 mg/kg)



Table S1F: Evaluation matrix for strength and relevance of aquatic persistence studies based on OECD Method 308 [3] and Method 309 [5]. Persistence in Water - Strength Yes

3 pts Attempted

1 pt No


a) Labeled or non-labeled soil for rate of transformation studies; labeled required for pathway studies (at least 95% pure test substances)

b) 90-110% recovery for labeled material, 70-110% recovery for un-labeled c) Information on water (origin/source, temperature, pH, sampling depth, appearance, DO, redox); if sediment is used, it should come from the same site as the water; water held at 4°C for not more than 4 weeks prior to testing

d) Tested in the dark under aerobic conditions and agitation at constant temperature (field temperature or 20-25°C)

e) At least 2 test concentrations; maximum not to exceed 100 µg/L, minimum <2 µg/L

f) Duplicate sampling at each time point

g) Duration not to exceed 100 d; incubation should be for 50-90% degradation h) LOD of at least 0.01 mg/kg in water or sediment or 1% of initial amount applied (whichever is lower)

i) Use of easily degraded reference substance (e.g., aniline, sodium benzoate) to validate results


Consensus Strength Score Persistence in Water – Relevance Yes

3 pts Attempted

1 pt No

0 pts a) Realistic rate of application (<1000 µg/L)



Table S2. Persistence of chlorpyrifos in soil reported in laboratory and field studies A. Persistence of chlorpyrifos in soil reported in laboratory studies conducted in Europe (score ≥50%)

Soil Type Half Life (d)

Concentration (mg/kg) Location Strength Relevance Reference

Sandy clay loam 43

1.28

Marcham, UK

24/24 3/3 [6] Loam 46 Thessaloniki,

Greece

Silty clay loam 95 Charentilly, France

Sand 111 Cuckney, UK Topsoil 99 100000 Sweden; Italy 15/24 0/3 [7] Geometric mean 73

B. Persistence of chlorpyrifos in soil reported in laboratory studies conducted outside of Europe (score ≥50%)



Gilford sandy clam loam (air dry, 25°C) 1.9

1 Illinois, USA 19/24 3/3 [8]

Gilford sandy clam loam (25% humidity, 25°C) 18

Gilford sandy clam loam (75% humidity, 25°C) 12

Gilford sandy clam loam (75% humidity, 35°C) 4.6

Hoopeston sandy clay loam (air dry, 25°C) 3.6

Hoopeston sandy clay loam (25% humidity, 25°C)

28

Hoopeston sandy clay loam (75% humidity, 25°C)

25





Hoopeston sandy clay loam ( (75% humidity, 35°C)

4.8

Ada B2 sandy loam (air dry, 25°C) 3.8

Ada B2 sandy loam (25% humidity, 25°C) 22



Ada B sandy loam (air dry, 25°C) 7.8

Ada B sandy (25% humidity, 25°C) 61

Ada B sandy loam (75% humidity, 25°C) 37

Ada B sandy loam (75% humidity, 35°C) 19

Sandy clay loam 3.8

1

Texas, USA

14/24 3/3 [9]

Clay loam 4.9 Texas, USA

Loam 5.6 North Dakota, USA

Loam 8.9 North Dakota, USA

Silty clay loam (Hastings, 2 yrs) 26 Nebraska, USA







Silt loam (Catlin, 2 yrs) 32 Illinois, USA Silt loam (Catlin, 3 yrs) 24 Illinois, USA Silt loam (Catlin, 4 yrs) 31 Illinois, USA Silt loam (Elburn, 2 yrs) 31 Illinois, USA Silt loam (Elburn, 3 yrs) 28 Illinois, USA Silt loam (Elburn, 4 yrs) 44 Illinois, USA Unknowna 7 25

Mumbai, India 13/24 0/3 [10] Unknowna 7 50 Unknowna 7 100 Sandy loam (2E formulation)a 21

1.47 New York, USA 13/24 3/3 [11] Sandy loam (2G formulation)a 21

Sandy clam loam 20 0.5 West Bengal, India 16/24

3/3 [12] Sandy clam loam 23 5 3/3

Sandy clam loam 37 50 3/3 Clay loam 28

12.5 Washington, USA 14/24 1/3 [13]

Silt loam (35°C) 42 Silt loam (25°C) 91 Silt loam 84 Silt loam (15°C) 175 Sandy soil 29 5 California, USA 15/24 3/3 [14]





Sandy loam 23 Clay loam (25°C med moisture) 30 10 Texas, USA

15/24

3/3

[15]

Clay loam (25°C med moisture) 30 100 Texas, USA

Sand (25°C med moisture) 450 10 Florida, USA

3/3 Sand (25°C med moisture) 450 100 Florida, USA aWhere ranges of values were provided and not specifically related to experimental conditions, the largest value was used

Geometric mean 21 C. Persistence of chlorpyrifos in soil reported in field studies conducted in Europe (score ≥50%)

Soil Type Half Life

(d) Concentration

(mg/kg) Location Strength Relevance Reference

Clay loam 2 0.64 Tivenys, Spain 12/24 3/3 [16]

Sandy clay loam 8 0.64 Tranent, Scotland 12/24 3/3 [17]

Clay loam 11 0.64 Charentilly, France 12/24 3/3 [18]

Sandy loam (spring) 15

>20 Belgium 16/24 0/3 [19] Sandy loam (summer) 18 Loamy sand (spring) 28 Loamy sand (summer) 30 Silt loam 27

Sandy silt loam 34 0.64 Valtohori, Greece 12/24 3/3 [20]


C. Persistence of chlorpyrifos in soil reported in field studies conducted in Europe (score ≥50%)



Loamy Silt 40 0.58

Lauter, Germany

13/24 3/3 [21] Loamy Silt 51 Herford,

Germany

Loam 55 0.58 Grebin, Germany 13/24 3/3 [22]

aWhere ranges of values were provided and not specifically related to experimental conditions, the largest value was used Geometric mean 20

D. Persistence of chlorpyrifos in soil reported in field studies conducted outside of Europe (score ≥50%)



Sandy clay 1.1 1.92 Brazil 13/24 3/3 [23] Sandy silt loam 1.5

3.1 Malaysia 14/24 3/3 [24] Sandy loam 1.1 Sand 1.2

Sand 3.5 6.25 Massachusetts, USA 12/24 3/3 [25]

Sandy loam 10 ~13 Illinois, USA 16/24 1/3 [8] Sand 14

1.1 Ontario, Canada 12/24 3/3 [26] Muck 56 Silt Loam 16 39 British

Columbia, Canada

12/24 0/3 [27] Silt Loam 17 53.5

Muck 35 0.5 New York, USA 12/24 3/3 [28]


D. Persistence of chlorpyrifos in soil reported in field studies conducted outside of Europe (score ≥50%)



Muck 42 1 Sandy loam 33

5.6 California, USA

12/24 3/3 [29] Loam 46 Illinois, USA Silt loam 56 Michigan, USA Loam 48

1.47 Washington, USA 14/24 3/3 [30]

Loam 80

Silt loam 87 Recommended Washington, USA 12/24 3/3 [31]

Geometric mean 13

E. Soil persistence studies excluded from the final assessment (score <50% or values not reported)

Study Type Soil Type Half Life (d) Concentration (mg/kg) Location Strength Relevance Reference

Laboratory Unknown (B) 1

4.18 Catania, Italy 5/24 3/3 [32]

Laboratory Unknown (A) 5

Field Sandy clay 2.8-7.2 4 Thailand 5/24 3/3 [33]

Field Loamy sand 4 0.37 Georgia, USA 10/24 3/3 [34]

Field Sand 5.7-7.6 3

Florida; Indiana, USA

11/24 3/3 [35] Field Loam 8.6-9.5

Field Silty clay (WG Formulation)

6.3 0.49 Metaponto, Italy 11/24 3/3 [36]




Field Silty clay (EC Formulation)

7.6 0.45

Field Sand 6.8 1.87 Florida, USA 9/24 3/3 [37]

Laboratory Sandy loam ~7 10 Ontario,

Canada 10/24 1/3 [38] Laboratory Unknown 18

Field Sandy clay 8.5 0.48 Hungary 7/24 3/3 [39]

Laboratory Clay Loam 9 0.9 Campo de Cartagena, Spain

9/24 3/3 [40]

Laboratory Loam 11

6.7

Mississippi; North Dakota; Indiana; Illinois; Virginia; California, USA; Germany

9/24 3/3 [41]

Laboratory Loam 22 Laboratory Silt loam 24

Laboratory Silty clay loam 34

Laboratory Loam 102 Laboratory Clay adobe 107

Laboratory 2:3 standard 141

Field Clay loam 13 3 Ontario, Canada 4/24 3/3 [42]

Laboratory Unknown 14.1-15.4 15

Ontario, Canada; Plainfield

4/24 0/3 [43] Laboratory Sand 19.8-31.5




Field Sandy loam 30 Unknown Malaysia 11/24 1/3 [44]

Field Sandy loam 35 3.34 Soviet

Union 10/24 3/3 [45] Field Sandy clay

loam 56

Field Sandy loam N/A, 36, 76 0.4, 2.9, 5.8 Sri Lanka 6/24 3/3 [46]

Field N/A 40 3.2 India 6/24 3/3 [47]

Laboratory Unknown 56 1, 10, 50, 100 North Carolina, USA

11/24 1/3 [48]

Field Sandy loam ~56 0.48 Budapest, Hungary 11/24 3/3 [49]

Laboratory Sandy loam 68.8-316.5

10, 100, 1000 Australia 8/24 0/3 [50] Laboratory Clay loam 197.5-320.9 Laboratory BS sand 93.5-338.1 Laboratory QSD sand 39-385.1 Laboratory MBU sand 104.5-825.2 Laboratory LQS sand 19.9-280.6

Field Clay loam ~84 5.4 Quebec, Canada 11/24 3/3 [51]

Laboratory Clay 120 0.1, 1 Oregon, USA 8/24 3/3 [52]

Field Loam Not reported 0.8 Italy 9/24 3/3 [53]




Field Silty clay loam Not reported 5.6 Nebraska;

Illinois USA 8/24 3/3 [54] Field Silt loam

Laboratory Sandy loam Not reported 50 Belgium 7/24 0/3 [55]

Field Sandy loam Not reported 44.9 Ontario, Canada 7/24 0/3 [56]

Laboratory Silt; sandy loam

Not reported 5

California; Minnesota; Michigan; Louisiana, USA

6/24 3/3 [57] Laboratory Clay Laboratory Clay loam

Field Clay Not reported 2 Texas, USA 6/24 3/3 [58]

Field Silty loam Not reported 0.18 South Africa 6/24 3/3 [59]

Field Muck Not reported 1.47 Ontario, Canada 4/24 3/3 [60]

Field Sandy loam N/A N/A India N/A N/A [61]

Field Clay N/A N/A Soviet

Union N/A N/A [62] Field Sandy clay

Laboratory

Canisteo

Not reported 5 Iowa, Illinois, USA 15/24 3/3 [63]

Tama Webster Readlyn Fayette Catlin




Ackmore Grundy Zook Muscatine

Laboratory

Clay loam 175

1000 (termiticide rate of application)

Texas, USA

15/24 0/3 [15]

Sand 214 Florida, USA Sand 1576 Florida, USA

Sandy loam 230 Arizona, USA

Sandy loam 335 Hawaii, USA


Table S3. Persistence of chlorpyrifos in sediment reported in studies conducted in Europe A. Persistence of chlorpyrifos in sediment reported in studies conducted in Europe (score ≥50%)

Study type Soil Type

Half Life (d)

Concentration (mg/kg) Location Relevance Strength Reference

Laboratory Sandy loam 22

0.77 Carrick, UK 23/27 3/3 [64] Laboratory Clay loam 51

Laboratory Great

Linford Loam

55 0.12 Bedfordshire, UK 16/27 3/3 [65]

Geometric mean 40

B. Persistence of chlorpyrifos in sediment reported in studies conducted outside of Europe (score ≥50%)

Study type Soil Type Half Life (d)


Laboratory Silty loam 5 0.05 North Vietnam 16/27 3/3 [66]

Field Clay loam 7 0.18 Brazil 16/27 3/3 [67]

Field Marine sediments 10.3 0.48 Mombasa,

Kenya 14/27 3/3 [68]

Laboratory Silty clay loam 30.5 0.44 Illinois, USA 16/27 3/3 [69]

Field Pond sediment 200 ~13 Illinois, USA 16/27 1/3 [8]


B. Persistence of chlorpyrifos in sediment reported in studies conducted outside of Europe (score ≥50%)



Geometric mean 19

C. Sediment persistence studies excluded from the final assessment (score <50%)



Laboratory Sediment 1 5.8 Catania, Italy 9/27 3/3 [32]

Laboratory Mesocosm gravel 7.4-14.5 0.0003, 0.009,

0.028

New South Wales,

Australia 12/27 3/3 [70]

Field Great

Linford Loam

20 0.02 Bedfordshire, UK 11/27 3/3 [71]

Laboratory San Diego

Creek sediment

20.3-223

10 California, USA 13/27 1/3 [72]

Laboratory Bonita Creek

sediment

23.7-57.6

Laboratory Estuarine sediment 24 0.73 Florida, USA 10/27 3/3 [73]

Field Sandy loam 30 N/A Maryland,

USA 10/27 1/3 [74]

Laboratory Commerce loam 39

6.7 Mississippi; California,

USA 9/24 3/3 [41]

Laboratory Stockton clay 51


C. Sediment persistence studies excluded from the final assessment (score <50%) Study type Soil Type Half

Life (d) Concentration

(mg/kg) Location Relevance Strength Reference

Field California ditch 58-144

Field runoff California, USA 9/24 3/3 [75]

Field California wetland 68

Field Pond sediment N/A 0.005, 0.025,

0.05, 0.5 California,

USA 12/27 3/3 [76]

Laboratory Silty clay N/A 2.5 Buenos Aires, Argentina 7/27 3/3 [77]


Table S4. Persistence of chlorpyrifos in water reported in laboratory and field studies A. Persistence of chlorpyrifos in water reported in laboratory studies conducted in Europe (score ≥50%)

Water source Half Life (d) Concentration (µg/L) Location Relevance Strength Reference

Microcosm water 6 0.5

Netherlands 16/27 3/3 [78] 6 5 10 0.05

Tox test water

1.3 1

Netherlands 16/27 3/3 [79]

1.3 0.1 1.3 0.01 1.3 1 1.3 0.1 1.3 0.01 1.9 1 1.9 0.1 1.9 0.01

Geomean 2.2

B. Persistence of chlorpyrifos in water reported in laboratory studies conducted outside of Europe (score ≥50%)


Creek water + gravel

1.3 6

New South Wales, Australia 20/27 3/3 [70]

2.3 20 3.0 0.2

10.4 0.25 13.8 1 14.4 0.2


B. Persistence of chlorpyrifos in water reported in laboratory studies conducted outside of Europe (score ≥50%)


15.2 20 17.3 2 18.0 0.05 18.0 6

Marsh water 28 5000 Ontario, Canada 18/27 0/3 [80] Canal water 1.5 1

California, USA 14/27 3/3 [81] Tap water 1.7 1 Patuxent R. 24 20

Maryland, USA 14/27 3/3 [82] Pocomoke R 27 20 Choptank R. 56 20 Susquehana R. 126 20

Geomean 11

C. Persistence of chlorpyrifos in water reported in field studies conducted outside of Europe (score ≥50%)


Microcosm water 7 15 Brazil 16/27 3/3 [67]

Estuary water 5 0.1 North Vietnam 14/27 3/3 [66]

Geomean 6


D. Persistence of chlorpyrifos in water reported in laboratory studies conducted with distilled water (score ≥50%, but excluded from the final assessment)


Distilled water pH 5.9 53 70

Georgia, USA 15/27 3/3 [83]


Distilled water pH 12.9 0.01 42








Distilled water pH 1 89 176



California, USA 14/27 3/3 [81]






D. Persistence of chlorpyrifos in water reported in laboratory studies conducted with distilled water (score ≥50%, but excluded from the final assessment)






Distilled water pH 7.1 74 5000 Ontario, Canada 18/27 0/3 [80]

Geomean 7.8 E. Water persistence studies excluded from the final assessment (score <50% or value not reported)

Study type Water source Half Life (d) Concentration

(µg/L) Location Relevance Strength Reference

Field Microcosm water 4 0.1, 1, 10, 100 Thailand 13/27 3/3 [84]

Field Field microcosm 10 75, 187.5 UK 12/27 3/3 [71]

Laboratory Distilled water 13-120 700 Oregon, USA 8/27 3/3 [52]

Laboratory Estuarine water 15-20; 22-24 500

Mississippi; Florida,

USA 13/27 3/3 [85]

Laboratory Distilled water 16-82 600, 370 Michigan, USA 10/24 3/3 [86]

Laboratory Aquaria water 18-23 100 Maryland, USA 9/27 3/3 [74]


E. Water persistence studies excluded from the final assessment (score <50% or value not reported) Study type Water

source Half Life (d) Concentration (µg/L) Location Relevance Strength Reference

Laboratory Distilled water 19-77 1000 Ontario, Canada 10/27 1/3 [87]

Laboratory Distilled

water; natural water

74; 25 1000, 500 Michigan, USA 11/27 3/3 [88]

Laboratory Natural water; tox test water N/A 500 Australia 12/27 3/3 [89]

Laboratory Laboratory water N/A 100, 500, 1000 Thailand 9/27 3/3 [90]

Laboratory Tox test water N/A 0.022, 0.065 Illinois, USA 14/27 3/3 [91]


Table S5. BCF values for chlorpyrifos reported for fish in the literature and reports (score >50%) A. BCF values for chlorpyrifos reported for fish in the literature and reports (score >50%)

Study type

Common name

Scientific name(s) BCF Duration

(d) Concentration

(µg/L) Location Strength Relevance Reference

Laboratory Sea bass Dicentrarchus labrax 0.6 7 200 Tunisia 19/33 4/6 [92]

Field Bluegill Lepomis macrochirus 100 33 0.41 MN, USA 16/30 3/6 [93]

Laboratory Jamaican red hybrid tilapia

Tilapia sp. 116 3 50 Jamaica 21/30 4/6 [94]

Laboratory Eel Anguilla anguilla 400 Kinetic 1.1-2.7 UK 22/30 6/6 [95, 96]

Laboratory Atlantic silverside;

Menidia menidia; 420 28 0.06-2.0 FL, USA 17/30 6/6 [96]

Laboratory Inland silverside

Menidia beryllina 440 28 0.25-2.0 FL, USA 17/30 6/6 [97]

Laboratory

California grunion fry; early life stage

Leuresthes tenuis 450 26 0.50-2.0, FL, USA 17/33 3/6 [98]

Microcosm Mosquitofish Gambusia sp. 472 6 + 5 1.44 CA, USA 21/33 4/6 [99]

Laboratory Carp Cyprinus carpio 550 14 0.49 Japan 18/30 4/6 [100]

Laboratory Tidewater silverside

Menidia peninsulae 580 28 0.12-0.5 FL, USA 17/30 6/6 [98]

Laboratory Gulf toadfish Opsanus beta 650 49 1.5-50 FL, USA 17/33 6/6 [101]

Field Fathead minnow

Pimephales promelas 780 18-33 0.14-0.46 MN, USA 16/30 3/6 [93]

Laboratory

California grunion fry; early life stage

Leuresthes tenuis 1000 35 0.50-2.0, FL, USA 17/33 3/6 [98]

Field Bluegill Lepomis macrochirus 1115 3 0.3-2.9 AR, USA 21/33 4/6 [102]


A. BCF values for chlorpyrifos reported for fish in the literature and reports (score >50%) Study type

Common name

Scientific name(s) BCF Duration

(d) Concentration


Field Largemouth bass

Micropterus salmoides 1344 3 0.3-2.9 AR, USA 21/33 4/6 [102]

Laboratory Rainbow trout

Salmo gairdneri 1374 30 + 16 0.3 MI, USA 30/33 4/6 [96]

Laboratory Guppy Poecilia reticulata 1589 Kinetic 0.9-3.7 Netherlands 17/30 6/6 [103]

Laboratory Fathead minnow

Pimephales promelas 1673 60 0.12-2.68 MN, USA 18/27 6/6 [104]

Laboratory Guppy Poecilia reticulata 1700 Kinetic 10 Netherlands 20/30 6/6 [105]

Laboratory Sheepshead minnow

Cyprinodon variegatus 1830 28 3.1-52 USA 20/30 3/6 [106]

Laboratory Jamaican red hybrid tilapia

Tilapia sp. 3313 2 5 Jamaica 21/30 4/6 [94]

Laboratory Zebrafish Danio rerio 3548 2+1 1 Spain 20/27 4/6 [107] Laboratory Gulf toadfish Opsanus beta 5100 49 12-200 FL, USA 17/33 6/6 [101]

Geomean 853 Smallest value omitted

B. BCF values for chlorpyrifos reported for fish in the literature and reports (score >50%) but not used Study type Species Scientific

name(s) BCF or

BAF Duration

(d) Concentration


Laboratory Carp Catla catla N/A 8 60-70 India 17/33 3/6 [108] Laboratory Carp Labeo rohita N/A 8 60-94 India 17/33 3/6 [108]

Laboratory Carp Cirrhinus mrigala N/A 8 110-130 India 17/33 3/6 [108]

Microcosm Mosquitofish Gambusia sp. N/A 33 0.11 USA 22/30 6/6 [109]


C. BCF values for chlorpyrifos reported for an amphibian, invertebrates, and plants in the literature and reports (score >50%)

Study type Species Scientific

name(s) BCF or

BAF Duration

(d) Concentratio

n (µg/L) Location Strength Relevance Reference

Laboratory Mollusc Venus gallina 3.4 4 1000-56000 Spain 20/33 1/6 [110]

Laboratory Mollusc Mytilus galloprovincialis

4.1 4 1000-56000 Spain 20/33 1/6 [110]

Microcosm, laboratory

Mosquito larvae

Culex quinqufasciatus (BAF)

45 33 0.11 USA 22/30 6//6 [109]

Laboratory Oligochaete Lumbriculus variegatus (BSAF)

57 10 1.75 Finland 18/33 6/6 [111]


Algae Oedogonium cardiacuin 72 33 0.11 USA 22/30 6//6 [109]

Laboratory Freshwater amphipod

Gammarus pulex (BAF) 412

1 + 3 depuratio

n 2.45 Switzerland 22/33 4/6 [112]

Laboratory Mollusk Crassostrea virginica 565

28 + 14 depuratio

n 0.61 USA 29/33 4/6 [113]


Snail Physa sp. 691 33 0.11 USA 22/30 6//6 [109]

Laboratory Water lettuce Pista stratiotes 3000 7 100-1000 Thailand 21/30 4/6 [90]

Laboratory Axolotl Ambystoma mexicanum 3632 2 50-100 Mexico 21/33 4/6 [114]

Laboratory Duckweed Lemna minor 5700 7 100-1000 Thailand 21/30 4/6 [90]

Geomean 204


D. BCF studies excluded from the final assessment (score <50% or value not reported) Study type Species Scientific

name(s) BCF or

BAF Duration

(d) Concen-

tration (µg/L) Location Strength Relevance Reference

Laboratory Spanish toothcarp

Aphanius iberus BMF 0.3 32 94 ng/g LW Spain 12/33 6/6 [115]

Laboratory Mosquito fish

Gambusia affinis 0.5 4 100 Spain 13/33 6/6 [115]

Laboratory Spanish toothcarp

Aphanius iberus 3.1 3 3.2 Spain 13/33 6/6 [115]

Laboratory Mosquito fish

Gambusia affinis 3.28 4 60 India 15/33 4/6 [116]

Laboratory Snapper Luthrimus fulviflama BAF 238 4 h 0.0082 Kenya 14/30 3.6 [68]

Laboratory Rabbit fish Seganus stellatus BAF 238 4 h 0.0082 Kenya 14/30 3.6 [68]

Laboratory Trout Oncorhynchus mykiss 997 28 0.3 [96]

Field Bluegill Lepomis macrochirus 1200 14 0.15 California,

USA 5/27 3/6 [117]

Field

Largemouth bass

Micropterus salmoides 1333 14 0.15 California,

USA 5/27 3/6 [117]

Field Black crappie

Pomoxis nigrom-aculatus

3333 14 0.15 California, USA 5/27 3/6 [117]

Field Channel catfish

Ictalurus punctatus 4667 14 0.15 California,

USA 5/27 3/6 [117]

In vitro Rainbow trout

Oncorhynchus mykiss 6760 1 0.4-4.0 g/L Australia 8/24 1/6 [118]

Field Nile tilapia Oreochromis niloticus N/A N/A N/A Ethiopia 7/27 4/6 [119]

Field African

sharptooth catfish

Clarias garienpinus N/A N/A N/A Ethiopia 7/27 4/6 [119]

Field African big barb

Barbus intermedius N/A N/A N/A Ethiopia 7/27 4/6 [119]

Field Common carp

Cyprinus carpo N/A N/A N/A Ethiopia 7/27 4/6 [119]



name(s) BCF or

BAF Duration

(d) Concen-


Field Catfish Rita rita N/A N/A N/A India 4/24 4/6 [120]

Field Catfish Mystus tengara N/A N/A N/A India 4/24 4/6 [120]

Field Carp Cyprinus carpio N/A N/A N/A India 4/24 4/6 [120]

Field Carp Labeo rohita N/A N/A N/A India 4/24 4/6 [120]

Laboratory Clam Katalysia opima 0.05 5 3000 India 11/30 1/6 [121]

Laboratory Green macroalgae

Glacilaria verycurosa 0.29 30 0.05 Vietnam 16/33 6/6 [66]

Laboratory Clam Meretrix meretrix 1 30 0.05 Vietnam 16/33 6/6 [66]

Laboratory Blue-green alga Anabaena sp. 18 5 1000-10000 India 13/33 6/6 [122]

Laboratory Blue-green alga

Aulosira tertilissima 397 5 1000-10000 India 13/33 6/6 [122]

Field Zooplankton N/A (ww BAF) 70 Field

collected 0.001 ng/L Canada 8/24 4/6 [123]

Field Zooplankton (lipid BAF) 3300 Field

collected 0.001 ng/L Canada 8/24 4/6 [123]

Laboratory Anisoptera Anax imperator 100 2 + 5-

dep. 0.9-17.6 Netherlands 0/30* 4/6 [124]

Laboratory Isopoda Asellus aquaticus 3242 2 + 5-

dep. 0.22-6.2 Netherlands 0/30* 4/6 [124]

Laboratory Diptera Chaoborus obscuripes 2428 2 + 5-

dep. 0.22-4.2 Netherlands 0/30* 4/6 [124]

Laboratory Ephemeroptera

Cloeon dipterum 1782 2 + 5-de. 0.03-1 Netherlands 0/30* 4/6 [124]

Laboratory Diptera Culex pipens 13930 2 + 5-dep. 0.1 Netherlands 0/30* 4/6 [124]

Laboratory Cladocera Daphnia magna 541 2 + 5-

dep. 0.01-3 Netherlands 0/30* 4/6 [124]



name(s) BCF or

BAF Duration

(d) Concen-


Laboratory Amphipoda Gammarus pulex (Adult) 2039 2 + 5-

dep. 0.02-0.6 Netherlands 0/30* 4/6 [124]

Laboratory Amphipoda Gammarus pulex (Juv) 3083 2 + 5-

dep. 0.1 Netherlands 0/30* 4/6 [124]

Laboratory Trichoptera Molanna angustata 5331 2 + 5-

dep. 0.1-25.6 Netherlands 0/30* 4/6 [124]

Laboratory Decapoda Neocaridina denticulata 1291 2 + 5-

dep. 5-653.4 Netherlands 0/30* 4/6 [124]

Laboratory Heteroptera Notonecta maculata 407 2 + 5-

dep. 1-53.14 Netherlands 0/30* 4/6 [124]

Laboratory Lepidoptera Paraponyx stratiotata 1601 2 + 5-

dep. 0.2-82 Netherlands 0/30* 4/6 [124]

Laboratory Heteroptera Plea minutissima 654 2 + 5-

dep. 0.9-17.6 Netherlands 0/30* 4/6 [124]

Laboratory Decapoda Procamarus sp. (Juv) 280 2 + 5-

dep. 0.2-82.01 Netherlands 0/30* 4/6 [124]

Laboratory Decapoda Procamarus sp. (Adult) 1295 2 + 5-

dep. 5-80 Netherlands 0/30* 4/6 [124]

Laboratory Heteroptera Ranatra linearis 392 2 + 5-

dep. 3.25-52 USA 14/30 6/6 [125]

Laboratory Megaloptera Sialis lutaria 9625 2 + 5-

dep. 0.2-625 Kenya 14/30 3/6 [68]

Microcosm Fanwort Cabomba caroliniana 600 1 5 Michigan,

USA 7/30 4/6 [126]

Microcosm Duckweed Lemna minor 640 1 5 Michigan, USA 7/30 4/6 [126]

Microcosm Goldfish Carassius auratus 1130 1 5 Michigan,

USA 7/30 4/6 [126]

Laboratory Eastern oyster

Crosetrea virginica 680 28 0.61 Maryland,

USA N/A N/A [127]

Laboratory Goldfish Carassius auratus 1134 2 50 Michigan,

USA 10/30 3/6 [128]

Laboratory Crustacean Artemia

partheno-genetica

6080 2 1-100 Spain 12/33 6/6 [115]



name(s) BCF or

BAF Duration

(d) Concen-


Laboratory Estuarine bivalve

Mercenaria mercenaria N/A 23 h N/A USA 16/33 4/6 [129]

Field Zebra mussel

Dreissena molymorpha N/A Field

collected 3.4-72.7 ng/L Italy 9/24 6/6 [130]

*These studies were assessed at zero strength because the radiolabel was in the incorrect location on the molecule.


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