Analysis, fate and risks of organic contaminants in river basins under scarcity Valencia, 7-8 February 2011 Introduction to EDCs and perfluorinated compounds: general environmental problems, regulations in US and Europe, toxic effects and environmental levels

Damià Barceló, Mira Petrovic, Marinella Farré

IDAEA-CSIC, Department of Environmental Chemistry, Barcelona, Spain ICRA - Catalan Institute for Water Research, Girona, Spain

Outline

1. EDCs Definition, History, Effects in wildlife and Mode of action, Compounds and sources EU and US legislation Specific groups of EDCs 1. Steorid sex hormones 2. Alkylphenolic non-ionic surfactans and related compounds 3. Phthalates 4. Brominated flame retardants 5. Polychlorinated compounds 6. Environmental levels, Determination of EDCs (general aspects)

2. Perfluorinated compounds Endocrine Disrupting Chemicals (EDCs)

“An exogenous substance that causes adverse health effects in an intact organism, or its progeny, consequent to changes in endocrine function” (European Commission)

“An exogenous agent that interferes with the synthesis, secretion, transport, binding, action or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis, reproduction, development and/or behaviour” (EPA)

History

Silent Spring Raquel Carson DES

1962 1979

1938 1985 1992 1996

McLachlan Colburn 1st evidence of the estrogenic activity of —Conferences— synthetic compounds (EC Dodds and W Lawson) 1st EU action The impact of endocrine disruptors on health and wildlife, Keybridge, UK 1997: “Our Stolen Future” by Theo Colburn indicates human and ecological dangers of EDCs

2000s: Global research efforts on EDC toxicity, occurrence, treatment strategies, and prevention

Well-documented effects in wildlife

• Decreased fertility & growth • Sex alteration • Poor hatching/egg shell thinning • Abnormal thyroid function

Some examples include: •reproductive effects in Baltic seals, •eggshell thinning in birds of prey, •decline in the alligator population in a polluted lake, •general declines in frog populations, •effects on the reproduction and development of fish, •development of male sex organs in female marine organisms such as whelks.

Aquatic animals are the most affected, especially carnivores, because they are at the top of the "food chain". Suspected effects in humans

• Malformations of newborns • Undescended testicles • Abnormal sperm • Low sperm counts • Abnormal thyroid function • Possible breast, testicular, prostate • Other effects

How do the EDCs act ?

Substances can interact with endocrine systems and cause a disruption to normal functions in several ways:

• They can act like a natural hormone and bind to a receptor. This causes a similar response by the cell, known as an agonist response. • They can bind to a receptor and prevent a normal response, known as an antagonistic response. • A substance can interfere with the way natural hormones and receptors are synthesized or controlled. EDCs Do Not Follow a “Typical” Carcinogenic Dose:Response Curve

“Safe” “Typical” Carcinogenic Response Response EDC Response

Dose

Timing of Exposure is Critical

SOME CATEGORIES OF SUBSTANCES WITH REPORTED ENDOCRINE-DISRUPTING PROPERTIES*

SUBSTANCE EXAMPLES USES MODES OF ACTION Naturally occurring Phytoestrogens Isoflavones; Present in plant material Estrogenic and lignans; coumestans anti-estrogenic

Female sex hormones 17-β ; Produced naturally in animals Estrogenic (including humans) Synthetic Polychlorinated Dioxins By-products from incineration Anti-estrogenic organic compounds and industrial chemical processes

Polychlorinated Dielectric fluids (PCBs)

Organochlorine DDT; ; Insecticides Estrogenic and pesticides anti-estrogenic Organotins Tributyltin Anti-fouling agent

Alkylphenols Used in production of NPEOs and Estrogenic polymers, degradation product Alkylphenol ethoxylates Nonylphenol ethoxylate Surfactants Estrogenic Phthalates Dibutyl phthalate (DBP); Plasticisers Estrogenic butylbenzyl phthalate (BBP) Bi-phenolic compounds Bisphenol-A Component in polycarbonate Estrogenic and epoxy resins Synthetic Ethinyl estradiol Contraceptives Estrogenic *Environment Agency, R&D Technical Summary P38, 1999. Potential Sources

Incineration, Landfill Polychlorinated Compounds - Polychlorinated Dioxins, Polychlorinated Biphenyls Industrial And Municipal Effluents Alkylphenolics (Surfactants and Their Metabolites): Nonylphenol Phthalates (Found In Placticisers): Dibutyl Phthalate, Butylbenzyl Phthalate Municipal Effluent And Agricultural Runoff Natural Hormones; Synthetic Steroids - 17-B-Estradiol, Estrone, ; Ethynyl Estradiol Pulp Mill Effluents Phytoestrogens - Isoflavones, Lignans, Coumestans Agricultural Runoff / Atmospheric Transport Organochlorine Pesticides DDT, Dieldrin, Lindane Agricultural Runoff Pesticides Currently In Use , Trifluralin, Permethrin Harbors Organotins: Tributyltin

EU Regulations

EU adopted Strategy for EDCs (March 30,2000) (5257/00)

‰ URGENT NEED to establish monitoring programs and to assess hazards and risks of EDCs ‰ Establishment of PRIORITY LIST of substances, i.e., EU 33 priority substances within Water Framework Directive include EDCs: Octylphenol, Nonylphenol and Di(2-ethylhexyl)phthalate (DEHP) ‰ In the medium-long-term, EU Directives for EDCs and identification of substitutes ‰ The whole approach is to be based on the PRECAUTIONARY PRINCIPLE EU Regulations Implementation of the EU Strategy for EDCs COM(2001) 262 , 14-06-2001

ƒ Establishment of a priority list of substances ƒ Legislative actions - Water Framework Directive - in 2 years (20 years, phase out) ƒ Sweden Workshop on EDCs, June 2001 recommendations on Monitoring were: ƒ Study “hot-spots” (near WWTPs), ƒ Fill the gap between research/monitoring

US Regulations

1962: Public Health Services Standard – EDCs such as arsenic, cadmium, and phenols 1974: EPA establishes Safe Drinking Water Act – Maximum Contaminant Limits (MCLs)

– Synthetic chemicals including pesticides

Recent US Legislation (Amendments): – Safe Drinking Water Act, Nov. 1995 – Food Quality Protection Act, Aug. 1996

1996: EPA forms the Endocrine Screening and Testing Advisory Committee (EDSTAC) US Regulations

EDSTAC – Purpose of EDSTAC: design a screening and testing program – Final report issued in August 1998 outlining a three tiered approach (screening/testing/assessment) for evaluation of over 87,000 compounds

1998 - On-Going – EPA’s Screening Program (EDSP) – EPA is conducting a mass screening of compounds to determine their endocrine disruption potential, if any.

2001 – Low-dose Peer Review – Evaluate reported low-dose reproductive and developmental effects and dose-response relationships – National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS)

Specific groups of EDCs

1. Steorid sex hormones 2. Alkylphenolic non-ionic surfactans and related compounds 3. Phthalates 4. Brominated flame retrardants 5. Polychlorinated compounds 6. Bisphenol A sex hormons

ESTROGENS PROGESTOGENS Natural hormones: Natural hormones: CH3 Estradiol OH Progesterone CH3 C O CH3 Estrone H CH3

H HO O Synthetic compounds: Synthetic compounds: Ethynyl estradiol Norethindrone Levonorgestrel OH OH CH 3 CH3 C CH C CH

H

H H

HO O

Contraceptive pills Birth-control pills

Estrogens (20 to 50 µg daily) – Ethynyl estradiol –

Progestogens (30 µg to 2 mg daily) – Ethynodiol diacetate 1 mg norethindrone acetate – Levonorgestrel 20-35 μg ethynyl estradiol – Norethindrone The “day-after” pill

750 μg levonorgestrel Uses (other than contraception)

• Estrogens: • Progestogens:

– Management of menopausal – Infertility and postmenopausal syndrome – Endometriosis – Physiological replacement – Certain breast and therapy endometrial – Prostatic cancer and breast – Menstrual disorders cancer in postmenopausal women

* Doses up to 400 mg daily

Environmental fate, toxicity and estrogenic effects of steroid sex hormones and related synthetic compounds

Biodegradation: synthetic estrogens are more persistent than natural estrogens

Half-life in surface water:estradiol <3-27 days ⇒ estrone ethynyl estradiol > 26 days Relative estrogenic potency (relative to 17β-estradiol)

Estrogen receptor Uterine weight Response of Vitellogenesis binding affinity doubling potency MCF7 cells

Estradiol 1.0 1.0 1.0 1.0 Diethylstilbestrol 0.4 2.5 0.1 Estrone 0.05 Ethynyl estradiol >1.0

Aqueous concentration that may induce estrogenic effects: 0.1-10 ng/L (E2, EE) Nonionic surfactants Alkylphenol ethoxylates

amphoterics cationics 2% 8%

nonionics 49% anionics other nonionics; APEO 9% 13% 41%

Fatty amine/acid ethoxylates; 13%

AEO; 65%

Alkylphenol ethoxylates

O OH - Non-ionic surfactants n industrial formulation (textile, n=1-20 tannery, pulp and paper industries) C9H19 - Pesticides adjuvants Nonylphenol ethoxylates - Paint ingredients (NPEOs) - Wetting agents

• Global production is well over 500.000 tons • Use restricted in many countries • Throughout northern Europe (Scandinavian countries, England, Germany) a voluntary ban on NPEO use in household cleaning products began in 1995, and restrictions on industrial cleaning applications in 2000 • South Europe - use in industrial formulations not restricted • USA, Spain – not restricted Breakdown pathway of NPEOs

C H 9 19 OCH2CH2OH 9

NP9EO C H Increasing toxicity 9 19 OCH2CH2OCH2COOH 8

NP9EC

C H 9 19 OCH2CH2OH 8 NP EO Increasing 8 persistence

NP2EO

NP2EC Increasing polarity NP1EO Increasing Possible contamination bioconcentration of groundwaters NP1EC NP C9H19 OH

Main concern - Reproductive toxicity of some degradation products

OH Alkylphenols (NP and OP) R O OH Short alkylphenol n ethoxylates R n=1-2 (APEOs) O OCH2COOH Alkylphenoxy n carboxylates R n=0-1 (APECs) Halogenated derivatives formed during chlorination (in the presence of bromide) at water treatment works X X X O OH O OH OCH COOH n n 2 R R R

Halogenated alkylphenol Halogenated Halogenated alkylphenoxy ethoxylates (XAPEOs) alkylphenols carboxylates (XAPECs) (XAPs) Halogenated alkylphenolic compounds

• Posses higher acute toxicity to Daphnia magna than non-halogenated precursors1

• Suspected mutagens2

• Halogenated nonylphenolic derivatives retain a significant affinity for the receptors suggesting that they may be able to disturb the hormone imbalance of exposed organisms3

1H. Maki et al., Environ. Toxicol. Chem. 1998 2M. Reinhard et al, Environ. Sci. Technol. 1982 3N. García-Reyero, V. Requena, M. Petrovic, B. Fischer, P.D. Hansen, D. Barceló, B. Piña Environ. Toxicol. Chem. 2004

Breakdown during sewage treatment (AST) (according Ahel, Wat. Res. 1995) Ultimate biodegradation of NPEOs <40% 40-45% ends up in secondary effluent 20 % in sludge

Primary Effluents Secondary Effluents Digested Sludge

7% 8% 5% 5% 20%

20%

47% 25% 68%

95% NPnEO NP1EC+NP2EC

NP1EO+NP2EO NP Average composition of nonylphenolic compounds after chlorination (calculated on a molar basis)

River water Chlorinated river water Flocculation sludge

13%

48%

NPEC NP NPEO halogenated derivatives

After: Petrovic et al. ES&T, 2003

Environmental fate, toxicity and estrogenic effects of alkylphenolic compounds

Toxicity EC50, 48 h (Daphnia magna) 1.5 mg/L (NPEO), 0.18 mg/L (NP) Bioconcentration factor: algae 6600-7700 (NP), 3500-5000 (NP1EO) mussel 3400 (NP)

The relative estrogenic potency (relative to 17β-estradiol) in-vitro (according Jobling and Sumpter, Aquatic. Toxicol. 1993) NP 9.0 x 10-6 OP 3.7 x 10-5 -6 NP1EC 6.3 x 10 -6 NP2EO 6.0 x 10 -7 NP10EO 2.0 x 10

Aqueous concentration that may induce estrogenic effect: 1-20 μg/L Estrogenic potential of halogenated alkylphenolic compounds

RYA Dose/response curves Relative affinity as calculated from the ELRA

Halogenated NPs – weaker estrogens than NP

Halogenated NPs – significant affinity for ER

Antiestrogenic assay Competition assay

Halogenated NPECs – strong Phthalates

Plasticizers used in the manufacturing of PVC, COO-R1 epoxy resins and cellulose esters, adhesive formulations - medical products, cosmetics, packaging of

COO-R2 food (limited extent)

Phthalates from the “Priority pollutant” list according to the US EPA

R1 R2 Name Acronym

CH3 Dimethyl phthalate DMP

CH2CH3 Diethyl phthalate DEP

(CH2)3CH3 Dibutyl phathalate DBP

(CH2)3CH3 CH2C6H5 Butylbenzyl phthalate BBP

CH2CH(CH2CH3)(CH2)3CH3 Bis(2-ethylhexyl) phthalate DEHP

C8H17 Di-n-octyl phthalate DnOP

Environmental fate, toxicity and estrogenic effects of phthalates

Biodegradation (decreases as the length of the alkyl chain increases) - sewage sludge inocula: >50 - 99% ultimate degradation, 28 days Primary degradation half-lives in surface <1 day to 2 weeks

Toxicity EC50, 48 h (Daphnia magna) 3.9 mg/L (DBP)

The relative estrogenic potency (relative to 17β-estradiol) in-vitro BBP 10-4 -10-6 DBP 10-5 -10-7 DEHP 10-5 In-vivo tests (mouse and rat) Endocrine disruptive effects observed for DBP, DEHP, BBP, DEP and DHP

Environmental risk limits ERL (sediment containing 10% organic matter) according to Wezel et al. Ecotoxicol. Environ. Saf. (2000) DEHP 1,000 μg/kg (fresh weight) DBP 700 μg/kg Brominated Flame Retardants (BFR)

Main types of BFR – Polybrominated (PBB) – Polybrominated diphenyl ether (PBDE) – Tetrabromobisphenol - A (TBBPA) – Hexabromocyclododecane (HBCD) – textiles

Classes of BFR Additive - mixed into polymers, not chemically bound to (PBB and PBDE) Reactive - chemically bound to plastic (TBBPA)

Uses - Plastic components of computers and televisions - Circuit boards - Seats of cars and buses - Textiles

Brominated flame retardants

Polybrominated biphenyls (PBBs) Polybrominated diphenylethers (PBDEs) 209 congeners 209 congeners

O

Brx Bry Brx Bry

x + y = 1-10 x + y = 1-10

Hexabromocyclododecane (HBCD) Tetrabromobisphenol A (TBBPA) 3 isomers

Br CH3 Br Br Br

Br HO CH3 OH Br Br Br Br Br

α-HBCD β-HBCD γ-HBCD Production of BRF

Estimated world market demand for PBDEs, TBBPA and HBCD in 1999 given in metric tons (www.bsef.com)

Penta-BDE Octa-BDE Deca-BDE TBBPA HBCD

America 8290 1375 24300 21600 3100 Europe 210 450 7500 13800 8900 Asia 0 2000 23000 85900 3900 Total 8500 3825 54800 121300 15900

- Penta-BDE ban in the European Union effective in 2003. - Penta-BDE consumption has already dropped in Europe, and a shift in production towards other BFRs like Deca-BDE and HBCD took place.

Hormone disrupting effects of BFR

Heating (for example during manufacture of plastics) and burning of materials containing PBBs, PBDEs and other brominated flame retardants can produce polybrominated dibenzo-p-dioxins and , which have similar toxicological effects to chlorinated dioxines

Low level exposure of young mice to PBDEs causes permanent disturbances in behaviour, memory and learning

PBDEs have been shown to disrupt the thyroid hormone system in rats and mice; these systems are a crucial part of the development of the brain and body

TBBPA is active in a breast cancer cell assay; its chemical structure is very similar to bisphenol A

TBBPA was found to high potential for out-competing the natural hormone, thyroxine. PCDDs, PCDFs and PCBs

Polychlorinated dibenzo-p-dioxins (PCDDs) Formed as a byproduct of: - Combustion processes 9 1 - Metal industry O 8 2 - Chemical manufacturing - Biological and photochemical 7 3 processes O 6 4 - Reservoir sources Cly Clx -high chemical stability Polychlorinated dibenzofurans (PCDFs) -high lipophilicity

BIOCONCENTRATION O BIOMAGNIFICATION

Clx Cly Electrical and flame-retardant properties; used in: Polychlorinated biphenyls (PCBs) -Hydraulic fluids -Electrical equipment 3 2 2´ 3´ - Sealants 4 4´ - Plasticizers 11´ - Paints 55´6 6´ Clx Cly - Adhesives - Casting agents

Estrogenicity of PCBs and Dioxines

The main oestrogenic effect of PCBs may be due to their hydroxylated metabolites, which are produced when the body attempts to break them down, in addition some PCB congeners may be anti-oestrogenic

Those metabolites with a para-hydroxylation on one of the rings are particularly effective at mimicking oestradiol, though others are also oestrogenic

Many PCDDs are known to be toxic and carcinogenic. PCDDs appear to be anti- estrogenic

Exposure to PCBs in food has been linked to delayed brain development and reduced IQ in children

Dioxins alter the Bisphenol A (BPA)

HO OH

Plasticizer

• Bisphenol A is used in the production of epoxy resins and polycarbonate plastics. These plastics are used in many food and drink packaging applications, whilst the resins are commonly used as lacquers to coat metal products such as food cans, bottle tops and water supply pipes

• Some polymers used in dental treatment contain Bisphenol-A.

Global production is more than one million tons per year

Hormone disrupting effects of BPA

• Bisphenol A was first shown to be oestrogenic in 1938, using ovariectomized rats

• More recently, it was found to be oestrogenic in the MCF-7 human breast cancer cell culture assay in 1993 • The hormonal effects could be measured at concentrations as low as 2-5 ppb (2-5 µg/l).

• Bisphenol A can also act as an antiandrogen, blocking the action of in a yeast screen containing a human androgen receptor In this screen bisphenol A was approximately as potent as , a well known anti-androgenic chemical.

• Bisphenol A produces identical effects to those produced by oestradiol on rat uterus and vagina; the vagina was particularly sensitive to the chemical

• It has been claimed that bisphenol acts in the same way as female hormones in the area of the developing rat brain which regulates fertility and sexual behaviour Environmental levels

Water samples - Wastewater - Suface water - Sea water

Solid samples - Sewage sludge -Soil - Sediment

Environmental levels – steroid sex hormones

Matrix (Location) Compounds Concentration (ng/l or ng/g) WATER Wastewater STP influent → effluent (Italy) Estrogens and progestogens 0.4-188 → 0.3-82.1 (Spain) Natural and synthetic estrogens <0.2-115 →<0.2-21.5 (The Netherlands) Natural and synthetic estrogens <0.5-140 →<0.4-47 River water (Germany) Natural and synthetic estrogens <0.1-5.1 (UK) Natural and synthetic estrogens <0.2-17 (UK) Synthetic estrogens/progestogens 2-17 (Spain) Estrogens and progestogens 0.2-71.1 (USA) Steriods and hormones 5-2000 (Canada) Steroids 2-67 Surface water (The Netherlands) Natural and synthetic estrogens 0.1-5.5 Drinking water (Germany) Natural and synthetic estrogens <0.1-2.1 (U.K.) Synthetic estrogens/progestogens <1-10 Seawater SOLID SAMPLES River sediment (Germany) Natural and synthetic estrogens <0.2-1.5 River sediment (Spain) Estrogens and progestogens 0.05-22.8 Activated and digested sludge (Germany) Natural and synthetic estrogens <2-49 Environmental levels – alkylphenolic compounds

Concentration Concentration (water) Matrix /location (sediment/soil) Compound μg/L mg/kg

Freshwater aquatic systems

Spain (Catalonia), water and sediment NPEO, NPEC, <0.1-31 (NPEO) 0.010-0.820 (NPEC) NP <0.1-15 (NP) 0.022-0.645 (NP) <0.1-35 (NPEC) Germany (Baden-Württenberg) NP, OP <0.01-0.49 (NP) <0.05-0.26 (NP) <0.01-0.19 (OP) USA and Canada (Great Lakes) NP, OP <0.01-0.92 (NP) 0.17-72 (NP) <0.005-0.084 (OP) <0.01-1.08 (OP)

<0.02-7.8 (NPE1O) <0.015-38 (NPE1O) USA streams (30 rivers) NP, NPEO <0.11-0.64 (NP) <0.003-2.96 (NP)

<0.06-0.60 (NPE1O) <0.003-0.17 (NPE1O) <1.6-14.9 (NPE3-17O) Italy (river Po) AEO - 0.15-1.05

Japan NPEO, NP, OP 0.04-0.42 (NPE1O) - 0.04-0.52 (NPE2O) <0.02-0.3 (NP) Soil

Sludge-amended soil NPEO, NP - 0.11—1.1 (NPE1O) 0.095—0.012 (NPE2O)

Sludge-amended soil NPEO, NP, OP - 0.07—1.21 (NPE1O) 0.08—0.39 (NPE2O) 2.35—4.61 (NP)

Environmental levels – alkylphenolic compounds

Concentration Concentration Matrix /location Compound (water) (sediment/soil) μg/L mg/kg

Marine and estuarine environment

Spanish coastal area AEO <0.1-15 0.037-1.3

CDEA <0.05-24 0.03-2.7

NPEO, NPEC, <0.2-11 (NPEO) 0.01-0.62 (NPEO) NP <0.15-4.1 (NP) <0.01-1.05 (NP)

Venice lagoon (Italy) – Estuarine water NPEO, NPEC 1.1-38.5 (NPEO)a - 0.6-102 (NPEC)

Krka estuary (Croatia) NPEO, NP <0.02-0.44 (NP1EO) - 0.1-0.7 (NP3-18EO) <0.02-1.2 (NP) English estuaries NPEO, NP, OP <0.6-76 (NP1+2EO) 0.16-3.97 (NP1EO) <0.08-5.8 (NP) 0.03-9.05 (NP)

Italy (Tiber estuary) PEG, MCPEG, 0.5-68 (PEG) - DCPEG <0.05-2.1 (MCPEG)

The Netherlands (Scheldt Estuary) NPEO, NP, 0.04-2.7 (NPEO) 0.04-0.25 (NPEO) NPEC 0.04-2.0 (NP)

USA (Jamaica Bay) NPEO, NP, 0.16-0.94 (NPEO) 0.05-30 (NPEO) OPEO, OP 0.077-0.42 (NP) <0.001-0.027 (BrNP)

Israel coast (sea water) NPEO <1.0-25 - Environmental levels – PBDEs

Matrix (Location) Compounds Concentration

Sediment Tetra- + Penta-BDEs 21 – 59 ng/g River sediments (Japan) BDE-47 490 ng/g Sediments downstream of a plastic industry (Sweden) BDE-99 750 ng/g BDE-100 170 ng/g BDE-47+99+100 nd – 9.6 ng/g Sediments from a river with textile industries (Sweden) BDE-209 nd – 360 ng/g Sum PBDE nd – 1.1 ng/g Sediment (Baltic Sea) BDE-47 <0.17 - 6.2 ng/g River mouth sediments (Europe) BDE-99 <0.19 – 7.0 ng/g

Sewage Sludge Sum PBDE 20 – 30 ng/g Digested sludge (Gothenburg, Sweden) Sum PBDE 0.4 – 15 ng/g Sewage sludge (Germany) BDE-47 39 – 91 ng/g Digested sludge (Stockholm, Sweden) BDE-99 48 – 120 ng/g BDE-100 11 – 28 ng/g BDE-209 140 – 350 ng/g

Biota Sum PBDE 26 – 1200 ng/g fat Fish from background areas (Sweden) BDE-47+99+100 19 – 4600 ng/g fat Fish (Sweden) Sum PBDE 2100 ng/g fat Osprey found dead (Sweden) Tetra- + Penta-BDEs 0.1 – 17 ng/g fat Marine fish and shellfish (Japan) Sum PBDE 18 -983 ng/g fat Freshwater fish (North-Rhine Westphalia) BDE-47 167 – 190 ng/g fat Salmon (Baltic sea) BDE-99 52 ng/g fat Sum PBDE 2.5 – 4.5 ng/g fat Cow s milk (Germany) ´ Sum PBDE 0.47 – 1.7 ng/g fat Reindeer and moose (Sweden) Sum PBDE 3.6 – 35.1 ng/g fat Chickens (US)

Human exposure to BDE-47

BABIES ng/Kg * day % Dermal contact 1.5 1.2 Diet 117.9 95.1 Inhalation 0.1 0.1 Dust 4.5 3.6 TOTAL 123.9 100 ADULTS ng/Kg * day % Dermal contact 0.1 10.5 Diet 0.6 63.1 Inhalation 0.0 2.7 Dust 0.2 23.7 TOTAL 0.9 100

Estimating human exposure to PBDE-47 via air, food and dust using Monte Carlo methods. T.Webster, V.Vieira, A.Schecter. Organohalogen Compds. (2005) 505-508. Feed contamination (for fish) by PBDEs

Fish farms

Wild fish

Market fish

Global assessment of polybrominated diphenyl ethers in farmed and wild salmon R.A.Hites, J.A.Foran, S.J.Schwager, B.A.Knuth, M.C.Hamilton, D.O.Carpenter. Environ. Sci. Technol. 38 (2004) 4945-4949.

Perfluorinated compounds (PFCs)

Perfluorinated = fully fluorinated

FFF F F F F O F

F F F F F F F OH

Ex. Perfluorooctanoic acid (PFOA , C-8)

Very stable (C-F bond energy 485 kJ/mol)

(C-C 346, C-N 305, C-O 358, C-Cl 327 kJ/mol) PFCs Most Common Structures

FFF O HO F O OH F F F FFF F F F F O n=3 - 9 Perfluorocarboxylic acids F S N

F F F F F F F O R R = methyl, ethyl FFF O Sulfonamides - F S O

F F F O n=2, 4, 6 F F F Perfluorosulfonic acids F

O FFF F F F n = 4, 6, 8 O - F P Phosphate acids O F F F OH OH n=4, 6, 8 Fluorotelomer alcohols FFF O

FFF F P R

F F F F R n = 2, 4, 6 F F F OH n=4, 6, 8 O Phosphinic / Phosphonic Telomer acids

PFCs Properties

ƒ Thermally stable (in excess of 150°C)

ƒ Resist degradation (acid, alkali, oxidizing agents, bio…)

ƒ Hydrophobic and oleophobic (3 phases in Kow)

ƒ Good surfactants, lubricants

ƒ Non-flammable

ƒ Chemically inert Due to PFCs properties are used in a plethora of industrial applications

carpet, upholstery, paper, textiles, cookware, paint, polymers, lubricants, flame retardants, pesticide formulations…

Due to PFCs properties are Globally Distributed (environmentally, biologically) PFCs Human Exposure Pathways (WATER- FOOD)

PFCs -Biological Effects

ƒ Biopersistence: PFOS and PFOA are the most studied and have been subject to restrictions in both manufacturing and use (3M, 2009). Currently, a high number of new PFCs are in use as alternatives, however these new PFCs can also breakdown to PFOS and PFOA, which would add to the reservoir of these persistent contaminants in the general environment

ƒ Bioaccumulation: PFCs accumulate in the , blood and breast milk (Lau et al., 2007), where it is primarily attached to proteins. In animal studies, PFCs are linked to bladder cancer (Alexander et al., 2003), liver cancer (Biegler et al., 2001), and developmental and reproductive toxicity (including neonatal mortality) (Lau, 2003) and impairment of thyroid, liver and immune system functions (Lau et al., 2007).

ƒ Exposure to PFCs can lead to increase in infertility for women (Biegler et al., 2001) and reproductive tract abnormalities: Cryptorchidism (undescended testicles) and alteration of puberty timing, specially when exposure occurred during early stages of development. PFCs are able to cross the human placenta (Inoue et al., 2004). PFCs - Concentration levels in Drinking water

519 598 PFOS (ng/L) 0.55 0.65 PFOA (ng/L)

18 2

3 2 80

8 1 1

7 2 3 1 58 57 8 2 5 2 8 3

PFCs - Drinking water

Germany

After detection of PFOA in drinking water at concentrations up to 0.64 μg/l in Arnsberg, Sauerland, Germany, the German Drinking Water Commission (TWK) assessed PFCs in drinking water and set for the first time worldwide in June 2006 a health‐ based guide value for safe lifelong exposure at 0.3 μg/l (sum of PFOA and PFOS).

New and shorter-chained PFCs (C4-C7) and their mixtures are being introduced as replacements. These "new" compounds could be main contributors to total PFC levels in drinking water in future. PFCs - Concentration levels in Food

PFCs - Concentration levels in Food

PFCs

The EFSA Journal (2008) Journal number, 653, 1‐131. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and their salts Scientific Opinion of the Panel on Contaminants in the Food chain