outline - people.unica.it - Università di Cagliaripeople.unica.it/mgpr/files/2009/01/fanelli.pdf · Roberto Fanelli, Maria UlaszewskaRoberto Fanelli, Maria, Elena Fattore Mario Negri

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



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…



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



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)



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)



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



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





The “grasshopper” effect (Wania and Mackay-1996)

“Grasshopper effect” + fat based diet = POPs body levels in Inuit > 10-20 fold higher than general population



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)



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).



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



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



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



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



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…



…..guilty until proofof innocence…

Definition for regulatory purposes

• PBT = Persistent, bioaccumulative and toxic

• vPvB = very persistent and very bioaccumulative



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…



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 !



Documents

outline - people.unica.it - Università di Cagliaripeople.unica.it/mgpr/files/2009/01/fanelli.pdf · Roberto Fanelli, Maria UlaszewskaRoberto Fanelli, Maria, Elena Fattore Mario Negri