Lead Relative Bioavailability in Lip Products and Their PotentialHealth Risk to WomenDi Zhao,† Jie Li,† Chao Li,† Albert L. Juhasz,‡ Kirk G. Scheckel,§ Jun Luo,† Hong-Bo Li,*,†
and Lena Q. Ma*,†,∥
†State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu,210046, People’s Republic of China‡Future Industries Institute, University of South Australia, Mawson Lakes, Adelaide, South Australia 5095, Australia§U.S. Environmental Protection Agency, National Risk Management Research Laboratory, Land Remediation and Pollution ControlDivision, Cincinnati, Ohio 45224-1701, United States∥Soil and Water Science Department, University of Florida, Gainesville, Florida 32611, United States
*S Supporting Information
ABSTRACT: Recent studies have investigated lead (Pb) concen-trations in lip products but little is known about its oral bioavailability.In this study, 75 lipsticks and 18 lip glosses were assessed for Pbconcentration, while 15 samples were assessed for Pb relativebioavailability (RBA, relative to Pb acetate absorption) using a mousefemur assay. Lead concentrations were 0.2−10 185 mg kg−1, with 21samples exceeding the Chinese limit of 40 mg kg−1. Samples withorange and pink colors and/or low cost contained higher Pbconcentrations. For samples with Pb > 7500 mg kg−1, Pb was presentdue to the addition of lead chromate (PbCrO4) as a colorant, whichwas confirmed by X-ray absorption near-edge structure analysis. Lead-RBA in 15 samples (87−10 185 mg kg−1) ranged from 23% to 95%,being significantly higher in moderate Pb (56−95%; 87−300 mg kg−1)than high Pb samples (23−48%; >300 mg kg−1). The calculation of Pb intake based on Pb-RBA showed that lip productingestion contributed 5.4−68% of the aggregate Pb exposure for women depending on Pb concentration. The high Pbconcentration in some lip products together with their moderate Pb-RBA suggests that lip product ingestion is a potential healthconcern to women.
■ INTRODUCTION
Lead (Pb) exposure is a common environmental hazard tohumans and is of great concern worldwide. Exposure to Pbcauses loss of appetite, and anemia and sometimes leads topermanent brain damage or even death.1,2 Pregnant womenand young children are particularly vulnerable to Pb exposure.It has been demonstrated that women’s blood Pb levels (BLLs)rise during pregnancy and lactation due to increased boneturnover, which releases stored skeletal Pb.3 Gulson et al.4
reported a 20% increase in BLLs during pregnancy in womenwith BLLs at 3 μg dL−1. In addition to being remobilized duringpregnancy, maternal skeletal Pb may be transported across theplacenta and enter fetal circulation.5 Increased fetal Pb exposurehas been linked with elevated incidences of low birth weight,miscarriages, and even fetal death.6,7 The risks of maternal Pbexposure to fetal health warrants study of Pb exposure forwomen of childbearing age.Lead exposure is complicated as it occurs from both dietary
and nondietary pathways.8 Food is the primary ingestion sourceof Pb exposure for the general population.9 However, exposurefrom nondietary sources such as incidental ingestion of Pb-
containing products may constitute a significant source. Animportant nondietary Pb exposure pathway for women ismouthing or ingestion of lip products such as lipsticks and lipglosses.10,11 Since different pigments have been used to producespecific colors in paints, it is likely that Pb may be added to lipproducts.12 Although a small amount of lip product is appliedeach time (∼10 mg), the number of daily applications may varydepending on the type of lip product and the habit of users.According to Loretz et al.,13 the average number of applicationsamong 311 women from the USA who regularly use lipstickswas 2.4; however, this may vary significantly (up to 20) withindividual circumstances. It has been estimated that a womanmay ingest ∼1.8 kg of lipstick inadvertently over a lifetime,14
which represents a significant Pb exposure pathway dependingon Pb concentration in lip products as well as oral Pbbioavailability (e.g., Pb fraction absorbed across gastrointestinalbarrier following ingestion).
Received: March 22, 2016Accepted: May 17, 2016Published: May 17, 2016
In recent years, Pb contamination in lip products has gainedincreasing attention. In 2007, Campaign for Safe Cosmeticsmeasured Pb concentrations in 33 brands of lipsticksmanufactured in the USA,15 with Pb being detected in 61%of products with the highest concentration of 0.7 mg kg−1. Onthe basis of microwave-assisted digestion, Hepp et al.16
reported Pb concentrations of 0.1−3.1 mg kg−1 in 20 lipsticksfrom the USA. A subsequent extensive survey of 400 lipsticksfrom the USA market by Hepp17 reported the highest Pbconcentration of 7.2 mg kg−1, averaging 1.1 mg kg−1. Thesereported values are below the US Food and DrugAdministration (FDA) limit of 20 mg Pb kg−1 in cosmetics.18
Similar studies found low Pb concentrations in lip productsfrom California, USA (n = 32; <0.03−1.3 mg kg−1), andHarbin, China (n = 30; 0.02−2.0 mg kg−1).10,11 In contrast,other studies have found high Pb concentrations (1154 and3760 mg kg−1) in some brands of lip products sold in Iran andSaudi markets.19,20
While studies have investigated Pb concentrations in lipproducts, studies measuring oral Pb bioavailability in lipproducts are scarce. When assessing Pb exposure via theingestion of lip products, previous studies estimated daily Pbintake based on total Pb concentration.10,11 While it is aconservative approach, conceivably, not all Pb in lip products isabsorbed into the bloodstream due to bioavailability con-straints.21,22 Therefore, exposure assessment based on total Pbconcentration may overestimate the risk associated with Pb inlip products. Reliable estimates of Pb exposure and health risksassociated with oral ingestion of lip products depend on thequantification of Pb bioavailability using in vivo assays.Therefore, the objective of this study was to (1) examine
total metal concentrations including Pb in 93 lip products, (2)determine Pb relative bioavailability (RBA, relative toabsorption of Pb acetate) in lip products using a mousefemur assay, and (3) assess the potential health risks of Pb in lipproducts to women based on Pb-RBA. Accurate assessment ofPb-RBA is an important step to understand the potential healthrisks of Pb in lip products to women via oral ingestion.
■ MATERIALS AND METHODSSample Collection and Preparation. A total of 93 lip
products, including 75 lipsticks and 18 lip glosses, werepurchased from retail stores or via the Internet in China. Lipproducts included popular brands and colors (orange, pink,brown, red, purple, green, and white), varying in price (0.7−29USD). Detailed information about lip products is provided inTable S1. Samples were stored at 4 °C until analyzed. The totalconcentrations of 7 metals (Co, Cd, As, Ni, Cr, Zn, and Pb) inlip products were determined using inductively coupled plasmamass spectrometry (ICP-MS, NexION300X, PerkinElmer,USA) following digestion of lip products (0.1 g) with repeatedadditions of concentrated HNO3 and H2O2 based on USEPAMethod 3050B. Although the HNO3/H2O2 method could notcompletely dissolve lip products due to the high wax and greasecontent, preliminary work suggested that Pb concentrations inlipsticks and lip glosses determined following the HNO3/H2O2digestion protocol were in good agreement with data derivedusing a microwave-assisted HNO3/HF method (Figure S1).Moreover, the HNO3/H2O2 digestion method has been widelyused for lipstick analysis.10,11,19
To better understand the source of Pb in lip products, typicalraw materials that are commonly used to produce lip productsincluding wax (n = 5), grease (n = 5), and pigments (n = 22)
were purchased from the Internet and analyzed for Pbconcentrations using ICP-MS following digestion with HNO3and H2O2. Waxes included beeswax, carnauba wax, cera alba,cera flava, and osmanthus wax; greases included castor oil,jojoba oil, coconut oil, palm oil, and olive oil while pigmentshaving orange, red, pink, purple, and brown colors werepurchased.
Assessment of Pb Relative Bioavailability. To date,there are no report of Pb relative bioavailability (RBA) in lipproducts following oral ingestion. One reason for the lack ofdata is the difficulty in replicating noneating exposure fromboth a methodological approach and an animal ethicsviewpoint. To circumvent these issues and to provide anestimate of Pb bioavailability following lipstick ingestion, twodifferent protocols may be utilized to administer materialduring animal bioassays, e.g., single gavage dose (which maynot be representative of lipstick exposure scenarios) andmultiple doses of the matrix via diet to achieve steady state. Thesteady state dosing approach provides an advantage ofmimicking daily continuous exposure. Although this approachhas not been utilized previously for the assessment of Pbbioavailability in lip products, it has been utilized for theassessment of arsenic- and Pb-RBA in contaminated soils.23−25
As a consequence, the steady state approach (e.g., lipsticksincorporated into mouse chow) was the most suitable for thedetermination of Pb-RBA in lip products.In this study, an in vivo mouse assay, utilizing Pb
accumulation in femur as the biomarker of Pb exposure wasused to measure Pb-RBA in lip products. Fifteen lip productswith Pb concentrations ranging from 87 to 10 185 mg kg−1
were assessed for Pb-RBA using female Balb/c mice with bodyweights of 18−20 g. Following acclimation for 1 week understandard animal housing conditions (12 h light/dark cycle, 25°C, and 50% humidity) with free access to Milli-Q water and arodent basal diet, mice were fasted overnight, weighed, andrandomly transferred to individual polyethylene cages prior toexposure.Lead acetate and lip products were supplied to mice in
amended diets. Initially, mouse basal feed was freeze-dried,ground to a powder, and then homogenized using a foodprocesser. Lead acetate solution was thoroughly mixed withmouse feed to achieve three Pb concentrations (5, 50, and 80mg Pb kg−1 dw). Lip products (∼1 g) were thoroughly mixedwith mouse feed powder at a ratio of 1:100 by grinding with amortar and pestle. Milli-Q water was then added to the mixtureof feed-lip product, which was made into a paste by kneading.The amended-feed was evenly divided into 21 portions afterwhich it was pelletized and freeze-dried. A preliminary studythat randomly selected pellets from a given amended-feedsample showed a relative standard deviation of <5% in Pbconcentration, indicating thorough mixing of Pb acetate or lipproducts with the feed.For Pb exposure, amended-feed (∼5 g dw) was supplied to
individually caged mice at 9:00 am every day. For each lipproduct and Pb acetate dose level, 3 separately caged mice wereused as a group. At the end of a 7 d exposure period, remainingfood was removed from cages and weighed with foodconsumption calculated as the difference between food suppliedand remaining. During the course of the experiment, mice hadaccess to Milli-Q water ad libitum. The 7 d exposure period wasselected as it was previously demonstrated that Pb accumu-lation in animals reaches a near steady state within 7−10 d.26
At the end of the exposure, mice were fasted overnight andthen sacrificed to collect femur samples by dissecting the hindlimbs from the trunk of the body and through the knee joint.This end point has been used as a biomarker of Pb exposure inanimals.26 Femur samples were immediately steamed tofacilitate the removal of muscle and connective tissue fromthe bone. After removal of tissue, the bone was freeze-dried andthen analyzed for Pb concentration using ICP-MS followingdigestion using concentrated HNO3 and H2O2 (USEPAMethod 3050B). Following zero correction, a linear doseresponse curve (DRC) of Pb concentration in femur wasestablished for Pb acetate exposed mice (Figure S2). Lead-RBAin lip products was calculated as the ratio of dose normalizedPb concentration in femur after lip product exposure to theslope of the corresponding DRC for Pb acetate (eq 1).
=×
×
Pb relative bioavailability (%)femur Pb after lip product exposure
Pb dose level via lip product slope of DRC100
lead acetate
(1)
Spectroscopic Assessment of Lip Products. To identifysources of Pb in lip products, two samples (#92 and #93) withthe highest Pb concentration (7781 and 10 185 mg kg−1
respectively) were analyzed by X-ray absorption near-edgestructure (XANES) spectroscopy at the Pb LIII-edge. XAS datawere collected at the Materials Research Collaborative AccessTeam beamline 10-ID, Sector 10, at the Advanced PhotonSource of the Argonne National Laboratory, United States.Detailed spectroscopic analysis is provided in the SupportingInformation.Human Health Risk Assessment. Assuming an ingestion
rate (IR) of 24 mg d−1 for a young Asian woman with bodyweight (BW) of 50 kg,10 daily Pb intake (DItotal and DIbioavailable,μg Pb kg−1 bw d−1) via lip product ingestion was calculated onthe basis of total Pb concentration (C, mg kg−1) and measuredPb-RBA (%) for the 15 lip products that were subjected tobioavailability assays as follows (eqs 2 and 3):
= ×CDI
IRBWtotal (2)
= × ×CDI
IR RBABWbioavalable (3)
The calculated daily Pb intake values were compared to theprovisional tolerable daily intake (PTDI) of 3.5 μg kg−1 bw d−1
to assess the potential risks of lipstick ingestion by women.27 Inaddition, the contribution of lip product ingestion to aggregatePb intake (considering Pb intake through dietary, ingestion ofsoil and dust, and inhalation of air) was assessed to quantify lipproduct ingestion to overall Pb exposure. Calculation of Pbexposure from dietary, soil, and air pathways is provided in theSupporting Information.QA/QC and Data Processing. During digestion of the lip
products using the USEPA 3050B, a cosmetics cream standardreference material (SRM) GBW09305 from the ChineseNational Standard Reference Center was included. Althoughthe matrix of the SRM was not lipstick or lip gloss, its similarityin composition with lip products made it suitable as a SRM forQA/QC. The accuracy of the HNO3/H2O2 digestion methodwas confirmed by an average Pb recovery of 34.2 ± 0.4 mg kg−1
(n = 3) from GBW09305 (37.2 mg kg−1). During measurementof Pb concentrations in digests of lip products and mousefemurs using ICP-MS, spiked and check samples (1−10 μg Pb
L−1) were included every 20 samples. The spike and checkrecoveries (n = 30) were 101 ± 6.5% and 99 ± 8.3%respectively.Lead concentration and Pb-RBA results were expressed as
the mean and standard deviation of 3 replicates. All graphs wereperformed using SigmaPlot (version 12.5, Systat Software Inc.,San Jose, CA, USA). One-way ANOVA was used to determinethe significant differences in concentration of different metals inlip products, Pb concentration in different raw materials, andPb-RBA between different lip products using SAS (version 9.1.3for Windows).
■ RESULTS AND DISCUSSIONPb Concentrations and Sources in Lip Products. Due
to daily exposure via ingestion, Pb in lip products has beenreceiving increasing attention. To determine whether lipproducts on the market in China are a source of Pb exposure,93 lip product samples, varying in color and price, werepurchased from retail stores or via the Internet. These sampleswere divided into two types, e.g., lipsticks (n = 75) and lipglosses (n = 18). Lead was detected in all samples, ranging from0.2 to 10 185 mg kg−1, averaging 497 mg kg−1 (Figure 1). All lip
products tested in this study exceeded the US FDA acceptablelimit of 0.1 mg Pb kg−1 in candy, which is likely to be consumedfrequently by children.19 Twenty-one out of the 93 samples(23%) contained Pb concentrations exceeding the FDA andChinese limits of 20 and 40 mg Pb kg−1, respectively, in coloradditives for cosmetics.18,28 Nine products had Pb concen-trations >1000 mg kg−1, with the highest being 10 185 mg kg−1.Compared to those of other metals in the lip products (Co, Cd,As, Ni, and Cr), Pb concentrations were significantly higher(Figure S3), suggesting Pb in lip products is of potential healthconcern.Type, color, and price are important factors influencing Pb
concentration in lip products. With respect to type, 11 out of75 lipstick samples (15%) contained Pb > 40 mg kg−1
compared to 10 out of 18 (56%) lip gloss samples (Figure2A). On the basis of color, orange and pink products containedhigher Pb concentrations than brown, red, and purple products(Figure 2B). Five out of 10 orange products (50%) contained>1000 mg kg−1 while 13 out of 37 pink products (35%)contained Pb > 40 mg kg−1. On the other hand, only 1 out of10 brown (10%) and 2 out of 26 red products (8%) had Pb >
Figure 1. Lead concentrations in 75 lipstick (+) and 18 lip gloss (▲)samples from retail stores and the Internet of China. The color of eachpoint in the figure represents the color in the lip products. The greendashed and red lines indicate the US Food and Drug Administrationlimit of 20 mg kg−1 and Chinese standard of 40 mg kg−1 for cosmetics.
40 mg kg−1, while Pb concentrations in 6 purple products werebelow the FDA limit of 20 mg kg−1 (Figure 2B). In addition tolip product type and color, Pb concentration in lip productstended to decrease with increasing price (Figure 2C). All lipproducts with Pb >40 mg kg−1 were <5 USD, while Pbconcentrations in samples costing >5 USD were below 20 mgPb kg−1.Previous studies have assessed Pb concentrations in lip
products from Europe and US, showing significantly lower Pbconcentrations than this study. Piccinini et al.29 reported Pbconcentrations of <0.1−3.8 mg kg−1 for 223 lip products from15 European countries, but showing higher Pb concentration inlipsticks (average 0.8 mg kg−1) than in lip glosses (0.4 mgkg−1). Similarly, more expensive lipsticks had lower Pbconcentrations. Hepp17 reported the average Pb concentrationin 400 lipsticks on the USA market was 1.1 mg kg−1. However,high Pb concentrations (2028−3760 mg kg−1) were observedin 3 brands of lipstick sold in Saudi markets.19 Similarly, a highPb concentration (1154 mg kg−1) was observed for one lipstickin Iran.20 However, lip products from the USA, Italy, andFrance did not show Pb concentrations above the FDA limit of20 mg kg−1,19 suggesting Pb contamination in lip productsshould attract more attention in developing countries wheresafety control is poorly enforced during manufacturing.It is known that metal contamination in lip products may
originate from natural or synthetic metal-containing ingre-dients.14 Gao et al.11 showed that lip products are often madeof the following materials: 20−30% wax, 50−70% grease, and5−15% pigment. Thus, typical wax, grease, and pigments withdifferent colors that are commonly used to produce lipproducts were purchased and analyzed for Pb concentration.Analyses showed that the raw materials contained lowconcentrations of Pb, although pigments (average 1.0 mgkg−1, n = 22) contained significantly higher Pb concentrationthan grease (average 0.01 mg kg−1, n = 5) or wax (0.04 mgkg−1, n = 5) (Figure 3A). In addition, little difference in Pbconcentration was found in pigments with different colors(Figure 3B). Hence, it can be concluded that high levels of Pbin the lip products were probably not caused by Pb from rawmaterials such as pigments, greases, and waxes.Some Pb minerals, including Pb tetroxide (red), Pb
monoxide (yellow), Pb chromate (yellow), Pb bromide(white), Pb iodide (yellow), Pb carbonate (white), and Pbsulfate (black), which are frequently used as colorants, might beadded by manufacturers, thereby leading to high Pb
concentrations in some cheap lip products.30,31 In this study,we found an association of high Pb with high Crconcentrations. For samples #1−72 with low Pb levels (<40mg kg−1), Cr concentrations were low (1−10 mg kg−1) withlittle variation among lip products (Figure S4A). However, forsamples #73−93 with high Pb concentrations (>40 mg kg−1),Cr concentration increased with Pb concentration. The molarratio of Pb to Cr in low-Pb lip products was <1 (0.04−0.75),while for high-Pb products, it was ∼1 (0.72−1.10) (FigureS4B), suggesting the presence of Pb chromate (PbCrO4) as anadditive to achieve orange and pink colors. The XANESanalysis of the two highest Pb orange samples (#92 and #93,7781 and 10 185 mg Pb kg−1) showed a close agreement inspectra between Pb in the lip products and PbCrO4 (Figure 4),confirming our speculation that Pb chromate was added to lipproducts.
Pb Relative Bioavailability in Lip Products. Reliableassessment of Pb exposure to women depends not only on totalPb concentration but also on Pb bioavailability in lip products.To date, reports of Pb-RBA in lip products are lacking,although one study showed an increase in blood Pbconcentration following oral daily gavage of a lipstick sample(19 mg kg−1 Pb) to rats for 12 weeks.20 To accurately quantifyPb exposure following ingestion of lip products, a mousebioassay was conducted to determine Pb-RBA in 15 lipproducts (8 lip glosses and 7 lipsticks) with Pb concentrationsranging from 87 to 10 185 mg kg−1. Low Pb lip products (<40mg kg−1) were not selected as it was difficult to accuratelyquantify Pb accumulation in mice at these concentrations.Mouse femur was used as the biomarker of Pb exposure, sincePb preferentially accumulates in bone compared to otherorgans/tissue during long-term exposure.32 Preliminary studiesdemonstrated that Pb accumulation in mouse femur followingPb acetate exposure was linearly dose dependent (Figure S2),confirming the suitability of using Pb-femur accumulationfollowing 7 d exposure to measure Pb-RBA in lip products.In this study, lip products with Pb concentrations of <40 mg
kg−1 Pb (Chinese limits) were considered as having low Pblevels, whereas 40−300 mg kg−1 Pb was moderate and >300 mgkg−1 was high. On the basis of femur as the biomarker of Pbexposure, Pb-RBA varied greatly from 23 ± 2.5 (#82) to 95 ±9.8% (#73), averaging 45% (Figure 5). Lead-RBA (56−95%)was significantly higher for products #73−77 having moderatePb concentration (87−299 mg kg−1) compared to 23−48% forproducts #78−93 having high Pb concentrations (325−10 185mg kg−1). For the two lip products (#73 and #75) with thelowest Pb concentrations (87 and 124 mg kg−1) among the 15samples, Pb-RBA was the highest (95 ± 9.8% and 70 ± 6.9%),
Figure 2. Variation in Pb concentration with lip product type (A),color (B), and price (C). Boxes represent the 25th to 75th percentileswhile solid and dashed lines in boxes denote the median and meanvalues, respectively. Error bars represent the 5th and 95th percentiles,and × signs represent the 1st and 99th percentiles, respectively.
Figure 3. Lead concentrations in raw materials of lip productsincluding pigments, grease, and wax (A) and variation in Pbconcentration with different pigment colors (B).
while significantly lower Pb-RBA values (34 ± 0.1% and 31 ±7.1%) were observed for products #92 and #93 with the highestPb concentrations (7781 and 10 185 mg kg−1). Excluding thesignificantly higher Pb-RBA for moderate-Pb lip products(#73−77), Pb-RBA showed little variation with Pb concen-tration and there was no significant difference (p > 0.05)between lip gloss and lipstick, averaging ∼40% (Figure 5).The significantly higher Pb-RBA values for moderate-Pb lip
products compared to high-Pb products may be due to theaddition of different Pb minerals to moderate-Pb lip products,which are more bioavailable than PbCrO4. Although XANESanalysis was not undertaken for lip products #73 and #75, theirmolar ratios of Pb to Cr (0.72−0.76) were <1 (Figure S4B),suggesting that Pb in the moderate-Pb samples was not presentas PbCrO4. Other Pb minerals, such as oxides or carbonate,with higher Pb solubility in gastrointestinal fluid compared toPbCrO4 (67−73% vs. 9%) were presumably used in these twoproducts,33 thereby leading to higher Pb-RBA. For futurestudies, analysis of Pb speciation in moderate-Pb samples
Figure 4. Normalized XANES spectra (a) and corresponding derivatives (b) for two lip product samples #92 and #93 with Pb concentration of 7781and 10 185 mg kg−1 and Pb chromate (PbCrO4).
Figure 5. Lead relative bioavailability in 15 lip products (8 lip glossand 7 lipstick samples) determined using mouse femur as a biomarkerafter 7 d of lip product exposure via diet. For samples #73−93, total Pbconcentration increased from 87 to 10 185 mg kg−1. Bars represent themean and standard deviation of three replicates.
Table 1. Estimated Daily Pb Intake Values for Women with Body Weight of 50 kg and Lip Product Ingestion Rate of 24 mg d−1
Based on Total Pb and Bioavailable Pb in 15 Lip Products
estimated daily Pb intake(μg kg−1 bw d−1) based on
contribution of lip product ingestion toaggregate Pb exposure (%) based on
sample total Pb (mg kg−1) bioavailable Pb (mg kg−1)a total Pbb bioavailable Pbc total Pbd bioavailable Pbe
aBioavailable Pb was the product of total Pb concentration and Pb relative bioavailability. bBased on total Pb concentration in the lip products.cBased on bioavailable Pb concentration in the lip products. dBased on total Pb in both lip product and other exposure pathways, which is describedin Table S3. eBased on bioavailable Pb in both lip product and other exposure pathways, which is described in Table S3. fBold values indicate theestimated daily Pb intake exceeding the PTDI of 3.5 μg kg−1 bw d−1.
should be undertaken to explain the variability in Pb-RBAamong lip products.Implications for Refining Risk Assessment for Women
Using Lip Products. When assessing Pb exposure via theingestion of lip products, previous studies rarely considered Pbbioavailability.10,11 In this study, we found that extremely highPb concentrations in some lip products (e.g., 10 185 mg kg−1)were due to the addition of PbCrO4 as a colorant (Figure 4).The high Pb concentrations together with moderate Pb-RBA(∼40%, Figure 5) make lip products an important Pb exposuresource for women using these products for adornmentpurposes.To quantify the contribution of Pb intake via lip products to
aggregate Pb exposure, we calculated daily Pb intake for womenthrough oral ingestion of lip products based on total andbioavailable Pb values. Only the 15 lip products that measuredfor Pb-RBA were included in the analysis. On the basis of totalPb concentration, daily Pb intake via the 15 lip products rangedfrom 0.04 to 4.9 μg kg−1 bw d−1 for a woman with body weightof 50 kg and lip product ingestion rate of 24 mg d−1 (Table 1).Oral ingestion of the three lip products with Pb concentrations>7000 mg kg−1 led to daily Pb intake close to or exceeding theprovisional tolerable daily Pb intake (PTDI) value of 3.5 μgkg−1 bw d−1.27 However, with the inclusion of Pb-RBA, daily Pbintake values were significantly reduced to 0.04−1.5 μg kg−1 bwd−1, with all values below the PTDI value. However, for a highrate of lip product ingestion (above the 95th percentile; 87 mgd−1),10 ingestion of some lip products (e.g., #93) may lead toPb intake (5.31 μg kg−1 bw d−1) exceeding the PTDI valueeven when Pb-RBA was incorporated into calculations. This Pbexposure scenario may potentially occur considering that somewomen may be required to wear lipstick or lip gloss as acondition of employment resulting in a higher number ofapplications per day compared to the general public.Ingestion of lip products is not the only Pb exposure pathway
for women. Lead may enter human body through inhalation ofair particulates, oral ingestion of soil and dust, and consumptionof water and food (e.g., rice, vegetables, and meat). Therefore,it is necessary to assess the relative contribution of lip productingestion to aggregate Pb exposure. Tables S2 and S3 show thecalculation of Pb intake through these pathways, with theassumption that Pb concentrations in these media wereequivalent to Pb guideline values based on Chinese environ-mental and food standards.34−37 Ingestion or inhalation ratesfor these media were adopted from Li et al.38 and Chen et al.,39
while Pb bioavailability was set as 50%, 10%, 10%, and 50% forinhalation, food consumption, drinking water, and soilingestion.39
On the basis of total Pb in lip products and other media, oralingestion of lip product #73 (87 mg Pb kg−1) contributed little(1.0%) to overall Pb exposure, whereas 56% of aggregate Pbexposure came from sample #93 (10 185 mg Pb kg−1) wheningested (Table 1). When taking Pb bioavailability intoconsideration for Pb exposure via lip product and otherpathways, Pb contribution from lip products increasedcompared to calculations based solely on total Pb concentrationdue to higher Pb biavailability in lip products than the defaultvalues for other Pb sources. Approximately 5% of aggregate Pbintake resulted from the ingestion of lip product #73, while thecontribution of lip product Pb to overall Pb exposure reached68% when lip product #93 (10 185 mg kg−1) was used. Ingeneral, oral ingestion of lip products with Pb concentrations>1800 mg kg−1 may lead to a contribution of >30% to
aggregate Pb exposure, while ingestion of samples with Pb <500 mg kg−1 contributed <10%.In addition, the health risk of Pb exposure to lip products for
women of childbearing age is of particular concern, asresearchers have shown that Pb previously accumulated inthe mother’s bones from past Pb exposure may be released intothe bloodstream during pregnancy.3,4 Released Pb may passthrough the placenta or be present in mother’s milk, therebyimpacting the fetus or infant’s developments.3 It was recentlyreported that the Pb maternal to fetal transfer ratio may be ashigh as 0.85.40 Therefore, excessive Pb intake via lip productsfor pregnant women or women prior to conception may subjectthe fetus and infant to elevated Pb exposure. Assuming that afemale uses lip products containing an average Pb concen-tration of 497 mg kg−1 (the average value of samples tested inthis study) and Pb-RBA of 40% from the age of 12 (with anaverage daily ingestion of 24 mg) and is pregnant at the age of25, a total of 22.6 mg of Pb will be absorbed from lip productsprior to pregnancy. The accumulated Pb via lip productingestion represents a source for remobilization, which has thepotential to impact the fetus or infant’s developments.3
Moreover, using XANES analysis, PbCrO4 was identified asthe dominant Pb specie in lip products with high Pbconcentrations. Hexavalent Cr (CrVI) is a well-recognizedcarcinogen. Presumably, when PbCrO4 in lip products wassolubilized in the gastrointestinal tract, CrVI may be available forabsorption into the systemic circulation, posing an additionalhealth risk. In this study, although Cr bioavailability was notdetermined, total Cr concentration in the 93 lip productsranged from 0.5 to 2736 mg kg−1 (Figure S4A). On the basis oftotal concentration, daily Cr intake via lip products ranged from0.01 to 65.7 μg d−1 for a woman with a lip product ingestionrate of 24 mg d−1. Ingestion of lip products containing Cr>1000 mg kg−1 would cause daily Cr intake exceeding therecommended daily Cr intake of 25 μg d−1 for women.41 SinceCr bioavailability in lip products was not performed, calculateddaily intake values may represent a worst-case scenario.However, Cr intake and bioavailability assessment from theuse of lip products may warrant further investigation.
■ ASSOCIATED CONTENT
*S Supporting InformationThe Supporting Information is available free of charge on theACS Publications website at DOI: 10.1021/acs.est.6b01425.
Descriptions of types, colors, and prices of the 93 lipproducts and estimated daily Pb intake through allexposure routes for adults (Tables S1−S3); comparisonof Pb concentrations determined using HNO3/H2O2 andthe microwave-assisted HNO3/ HF methods, linear doseresponse of Pb accumulation in mouse femur followingPb acetate exposure, concentration of other metals in thelip products, and molar ratio of Pb to Cr in lip products(Figures S1−S4). (PDF)
This work was supported in part by Jiangsu ProvincialInnovation Team Program and Jiangsu Provincial Double−Innovation Program.
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