Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 1
EnvironmentalEnvironmental Contamination, Contamination, POPsPOPs and and Human exposureHuman exposure
Roberto Fanelli, MariaRoberto Fanelli, Maria Ulaszewska, Elena FattoreElena Fattore
Mario Mario NegriNegri Institute for Pharmacological Research, Milan, ItalyInstitute for Pharmacological Research, Milan, Italy
Chemicals and their residues in Food and Water,Piacenza November 13-14 2008
outline
• POPs: a definition• Origins and fate of POPs in the environment• From environment to man• POPs exposure : concerns• Regulatory trends
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 2
Persistent (definition1)
Existing for a long or longer than usual time or continuously: as continuing without change in function or structure ……or effective in the open for an appreciable time usually through slow volatilizing ….or degraded only slowly by the environment <persistent pesticides>
Merriam-Webster Dictionary
Persistence.. just a feature ofsome man made compound ?
• Some natural compounds show high persistence in the environment.
• Fossil fuels, hair, bones, wood, proteinsequences refractory to enzymatic cleavage, metals…
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 3
Definition 2
“Persistent Organic Pollutants (POPs) are chemical substances that persist in the environment, bioaccumulate through the food web, and pose a risk of causing adverse effects to human health and the environment.”
UN Environment Program http://www.chem.unep.ch/pops/
A bit of history…• First generation pesticides (As, HCN) ineffective
and highly toxic• First important “second generation” pesticide was
DDT• Synthetized by Paul Muller (1939)• Toxic to a wide range of insects pests (broad
spectrum)• Persistent ( no need for frequent applications )• Insoluble in water (not washed out by rains)• Inexpensive and easy to apply
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 4
history continues…
• Effective in killing pests and boosting crop yields
• Widespread use around the globe
• Also non agricultural uses (de-lousing WWII soldiers, malaria control, mosquitos control in residential areas)
• Paul Muller awarded Nobel Prize for discovery ofDDT (1948)
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 5
bad news…(for DDT…)• Rachel Carson publishes “Silent Spring” (1962)• Data on toxicity to non target organisms ( birds, insects,
aquatic organisms..)• Introducing the concept of indirect toxicity due to
bioconcentration and biomagnification.• Many birds predator populations such as bald eagles,
brown pelican and peregrine falcon almost disappeared.• Atmospheric long distance transport to pristine areas
( measured in seals and esquimos..)• Birth of the environmental movement..• US cancel DDT registration ( 1972)
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 6
in the meantime…
• Pesticides (Organochlorine pesticidesDDT..+ others)
• Industrial chemicals (PCBs…PBDEs, PFOS)
• Inintentional byproducts (dioxins furans…)
• Aldrin/Dieldrin• Benzo(a)pyrene• Cadmium• Chlordane• DDT, DDD, DDE• Dicofol• Dioxins (TCDD) &
Furans• Endrin• Endosulfan• Hexachlorobenzene
Persistent Chemicals I
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 7
Persistent Chemicals II
• Heptachlor• alkyl-lead • Lindane• Mercury • Methoxychlor• Mirex• Octachlorostyrene• Polychlorinated biphenyl’s
(PCBs)
Persistent Chemicals III
• Pendimethalin• Pentabromo diphenyl ether• Pentachloronitrobenzene• Polybrominated Hydrocarbons• Polycyclic aromatic hydrocarbons
(PAHs)• Tin (organotins)• Toxaphene• Trifluralin• 1,2,4,5-tetrachlorobenzene
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 8
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 9
The “grasshopper” effect (Wania and Mackay-1996)
“Grasshopper effect” + fat based diet = POPs body levels in Inuit > 10-20 fold higher than general population
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 10
POPs levels in general populationMaternal milk Blood /serum
PCDD e PCDF(Dioxins&Furans)
9-15 pg TEQ/g fat(Abballe et al., 2008)
8-11 pg TEQ/g fat(De Felip et al. 2008)
PCB-DLPCB- NDL
11-19 pg TEQ/g fat(Abballe et al., 2008)50-219 ngΣ6PCB/g fat(Polder et al, 2008)
15-21 pg TEQ/g fat240-470 ngΣ6PCB/g fat(De Felip et al. 2008)
PBDE 76,3±308 ngΣPBDE/g fat(Johnson-Restrepo, 2007)
0,4-41ngΣPBDE/g fat(Hites, 2004)
PFOSPFOA
0,01-0,4 ng/mL0,05-0.61 ng/mL(Fromme et al, in press)
6,4-107 ng/mL<1-41,5 ng/mL(Fei et al., 2007)
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 11
How has the TDI been calculatedfor dioxins
(Tolerable Daily Intake)?
Critical toxicological effects : developmental (reproductive and nervous system)
Experiments done with experimental animals exposed prenatally and during lactation
Critical Toxicological Effects ( dioxins):developmental toxicity (reproductive and
nervous systems)1. Decreased sperm count in male offspring of Holzman rats (Mably et
al., 1992).
2. Accelerated eye opening and decreased sperm count in male
offspring of Long Evans rats (Gray et al., 1997).
3. Decreased sperm production and altered sexual behaviour in male
offspring in Wistar rats (Faqi et al., 1998).
4. Decreased anogenital distance in male offspring in Holzman rats
(Ohsako et al., 2001).
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 12
Specie Effects NOAELng/kg bw
LOAELng/kg bw(Single dose)
Estimated maternal body burden(ng/kg bw)
Associated EHDI(pg/kg bw-day)
Holzman rats
Decreased sperm count in male offspring
64a 100c 50
Long Evans rats
Accelerated eye opening and decreased sperm count in male offspring
50a 80c 40
Wistar rats
Decreased sperm production and altered sexual behaviour in male offspring
25b 40c 20
Holzman rats
Decreased anogenital distance in male offspring
12.5a
50a20d
80d10
Mably et al., 1992; Gray et al., 1997; Faqi et al., 1998; Ohsako et al., 2001asingle bolus dose; b maintenance dose; c 15GD; d16GD
Pivotal Studies For Risk Assessment
Estimated Human Daily Intake:(EHDI): 10-50 pg WHO-TEQ/kg bw-day
FIEHDITDI =
1) Estrapolation from animal to man (No FI)2) Interindividual variability in human population (FI = 3.2)
3) LOAEL instead of NOAEL (FI = 3)
dayTEQ/kgbw-WHO 2pg −=
TWI = 14 pg WHO-TEQ/kg bwWeekly TDI
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 13
Country PCDDs +PCDFs
DL-PCBs Total TEQs References
Belgium b,c 1.00 1.04 2.04 Focant et al., 2002
Finland d 0.79 0.74 1.53 Kiviranta et al., 2004
Italy d 0.96 1.30 2.28 Fattore et al., in press
Japan c 0.89 1.36 2.25 Tsutsumi et al., 2001
Norway d,e 1.21 1.52 1.73 Becher et al., 1998
Spain (Catalonia) f,g 1.36 Llobet et al., 2003
The Netherlands c 0.6 0.5 1.1 Baars et al., 2004
USA f 1.67 0.65 2.32 Schecter et al., 2001
(a)Rounding off to a maximum of three figures. (b)Only non-ortho dioxin-like PCBs included.(c)Lower bound.(d)Upper bound.(e)I-TEQs.(f)Medium bound.(g)Dioxin-like PCBs not included.
Mean dietary intake estimates (pgWHO-TE/kg-bw per day) for adults in different Countries
Dioxin intake in the italian general population
0
5
10
15
20
25
0 20 40 60 80 100Age (years)
pgW
HO
-TE/
kg-b
w da
y
2.3 pg WHO-TEQ kg bw-day
High percentiles, 2-3 times average value
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 14
High levels(Yusho and Yucheng incidents)
•Increased prenatal mortality,•Low birth weight,•Developmental delays•Behavioural disorders•Hearing loss•Alteration in sexual behaviours
Prenatal exposure to dioxin-like compounds seems to cause persistent changes
Background levels (USA, The Netherland)
•Thyroid and immune systemalterations,
•Neonatal hypotonia, •Neurobehavioral outcomes (hyperactivity, slower time reactions, lower IQ score)
•Feminised play
PCB non–dioxin-like possibly involved
What environmental levels for general population ?
• Estimated average dietary intake for European population: 1.2-3 pg/kg bw-day (body burden: 2-5 ng/kg bw).
• Estimated body burden for the US population: 5 ng/kg bw (obtained from 3 pg/kg bw-day).
Exceeding of TWI for consistent part of the general population
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 15
Most sensitive groups
Fetuses Infants Children
• The highest sensitivity in the adverse responses is during the developmental period.
• The large species differences in the sensitivity to dioxin is greatly reduced in the developing organism.
Higher exposure in comparison to their body weight
Rationale for a stricter regulation
• A “safe” environmental concentration cannot be established with sufficient reliability according to current procedures
• Long term, environmental accumulation difficult to reverse can happen with unpredictable results
• Remote areas should remain untouched• Very persistent and very bioaccumulative compounds can
end in high and unpredictable levels in humans and animals with unpredictable long term effects
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 16
Comparison between Second and Third round of WHO coordinated exposure study
Belgium
Croatia
Czech
Rep
ublic
Finlan
d
German
y
Hunga
ry
Norway
Russia
Slovak R
epub
lic
Spain
Ukraine
2000-2003
1992-1993
0
5
10
15
20
25
30
WHO
-TEQ
pg/
g of
fat
Levels of PCDDs/Fs in human milk. WHO coordinated exposure study 1992-2003
2000-20031992-1993
Priority lists…
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 17
…..guilty until proofof innocence…
Definition for regulatory purposes
• PBT = Persistent, bioaccumulative and toxic
• vPvB = very persistent and very bioaccumulative
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 18
toward a stricter regulation….P = t 1/2 > 60d in marine water or
> 40d in freshwaters or> 180d in marine sediments or> 120d in freshwater sediments
vP = t 1/2 > 60d in marine water or freshwater or> 180d in marine or freshwater sediments
B = BCF > 2000vB = BCF > 5000T = NOEC < 0.01 mg/l or CMR or ED
well, then we can relax…….(unfortunately..not)
• Reach will take a long time to have effect..• A new type of “persistent pollutants “ have been
identified:• Compouds steadily released into the environment
through the wastewaters treatment plants (pharmaceuticals, consumer products..) even if not persistent for their chemistry give a constant exposure because of their constant release…
Chemical residues in food and water; challenges for a future sustainable agriculture
MGPR 2008 - Piacenza (Italy), 13 and 14 November 19
conclusions
• Environmental persistency is now well recognized as a negative feature of chemical substances
• Evident adverse effects on wildlife and humans seems to belong to past
• More subtle adverse effects on endocrine homeostasis bound to in utero exposure are now considered the most sensitive endpoint for toxicity
• While exposure of the general population to POPs is decreased , sensitive subgroups, are still exposed to amounts higher than TDI.
Thanks for your attention And
Good luck !