Endocrine disruptors Anses risk assessment activities EU-OSHA - PowerPoint PPT Presentation

Endocrine disruptors Anses risk assessment activities EU-OSHA workshop Workplace risks to reproductivity : from knowledge to action 16 January 2014 1

Background history and context In 2009, Anses was asked by French ministries to: Identify products and/or articles containing potential endocrine disruptors (ex.  Bisphenol A, Phtalates, Perfluorinated compounds…) Estimate human exposures to these EDs in particular pregnant women and/or  newborns or infants Conduct a Human health risk assessment :  Reproductive effects: fertility or developmental abnormalities on the • reproductive development (eg. cryptorchy, hypospadia…) and/or Endocrine effects (specifically for reproductive endocrine disruption). • For BPA to conduct a complete Human health risk assessment including effects on  the thyroid organ, the immune system, neuro-development, diabetis, obesity…). General population and occupational setting  2

Reports on BPA and related compounds 2013 http://www.anses.fr/en/content/bisphenol-anses-demonstrates- potential-health-risks-and-confirms-need-reduce-exposure Risk assessment of Bisphenol A (BPA) on human health • Other Bisphenols (S, F, M, B, AP, AF, BADGE) • BPA substitutes overview : hazards and uses • Social representations: an analysis of uncertainties and their interpretations on • Endocrine disruptors definition and criteria 3

ED Risk assessment reports under completion 5 substances in consumer goods : • Chemical compounds Production and uses •N hexane Glues, paint, varnish, lubricants, etc. : out and indoor air toluene Glue, degreasing agents, car air fresheners, etc.: out and indoor air MTBE Motor fuel : out and indoor air Quaternium 15(Q15) Mosquito repellents, detergents, adhesives, etc.: Out and indoor air o-phenylphenol (OPP) Air freshener, sanitizers and cleaning agents, etc. : out and indoor air 4

Pending ED reports (2014) 6 substances for which toxicological profiles and exposure data are being • assembled : the relevance of performing RA will depend on the identification of exposure situations Chemical compounds • •4-nitrophenol 4-tert-octylphénol DEGME 4-tertButylPhénol 4-nonylphénol Chlorocrésol Occupational exposure limits • BPA 2014 • BBP under review • DEHP and DBP adopted, to be submitted to public consultation soon in 2014 • 5 •

EDs under priorization for RA • Perfluorinated : • PHTALATES •Di-n-butylphtalate : DBP •PFOA •Diisobutylphtalate : DIBP •PFOS •Butylbenzylphtalate : BBP •Diethylhexylphtalate : DEHP, •Diisononylphtalate : DINP •Diisodecylphtalate : DIDP • Polybrominated : •Diisopentylphtalate :DIIP •Dipropylphtalate •2,2’,4,4’-tetrabrominated •Mono-n-butylphtalate diphenylether (2,2’,4,4’-tetraBDE) •Di-n-hexylphtalate •Di-2propyl-heptylphtalate : •Decabrominated diphenylether DPHP (DecaBDE) •Diisoundecylphtalate : DIUP •Dicyclohexylphtalate : •Diisooctylphtalate : DIOP •Ditridecylphtalate : DTDP 6

BPA Effects and associated Toxicological Value selected for the RA Internal TV Internal NOAEL by by application of a application of a Margin of Safety LOAEL NOAEL* bioavailability Study Route of (MOS) of 300 on Critical effects factor of 3% reference exposure the internal NOAEL (µg/kg/d) (µg/kg/d) (µg/kg/d) (µg/kg/d) Brain and Xu et al. , oral / 50 1.5 0.005 behaviour 2010c Female Rubin et al. , reproductive oral / 100 3 0.01 2001 system Metabolism and Miyawaki et oral 260 87 2.6 0.009 obesity al. , 2007 Moral et al. , Mammary gland oral / 25 0.75 0.0025 2008 7

Conceptual diagram for BPA exposure assessment  On the basis of BPA uses report (Anses, 2011) Oral exposure Cutaneous Inhalation Non EU uses Surface and Drinking Food and Outdoor Outdoor Domestic Indoor air undergrounfd water beverages dust air soil water fungicide products food contact Tyres,brake Lacker, furniture– cosmetics Dental Water materials Various Thermal fluid, Medical varnish, construction devices fillings pipes and goods** paper hydraulic paint, etc mateirials containers fluid Environmental releases (industry, sewage, water treatment plants, etc.) Antioxidant Tying products flame Developer for Other Other Epoxy Antioxidant in Polycurethane plasticizers, retardant thermal polymers resins resins in pollyvinyl automobile hardeners reagent paper chloride industry Bisphenol A ** : CD, DVD, computers, screens, household electric appliances, small electric equipment, cell phones, optical equipment, sportswear, etc.

Exposure assessment methodology Identification of sources, compartments and routes of exposure ฀ litterature, inventory of • uses based on a survey of industries that targeted French companies; BPA contamination data ฀ litterature, specific French surveys commissioned by the Anses • in order to document BPA concentration in indoor air, settled dust, drinking water, food and thermal receipts; Development of exposure scenarios • Several studies document levels of BPA in thermal receipts (Biedermann et al. 2011 , EWG • 2010, Mendum et al . 2010, etc.). However none of them relate to thermal receipts disributed in France Anses coordinated a study : 50 receipts ( sept.-oct. 2011) • 9

BPA contamination data : thermal receipts Östberg et Noaksson, SCL, 2011 Biedermann et EWG, 2010 Danish EPA, Mendum et Schreder, Liao and Kannan, Geens et al ., 2012 2010 cité dans al. , 2010 2011 al. , 2010 2010 2011b Danish EPA, 2011 Country France Switzerland USA et Japan Danmark Sweden USA USA USA, Japan, Korea Belgium Vietnam Supermarkets, Chromatograms Shops, Récolte par 4 Supermarkets, shops, stations- shops, supermarkets, familles shops, banks, Sampling places Supermarkets, Shops and Banks, shops, Not precised service, banks cinemas… public institutions suédoises stations service, shops, banks restaurants restaurant, restaurants, fast- parkings… food Number of 50 13 36 12 16 22 103 44 10 (tickets non receipts tested imprimés) Number of 36 11 16 9 8 11 97 44 receipts with BPA (soit 72 %) (soit 85 %) (soit 44 %) (soit 75 %) 100 % (soit 80 %) (soit 50 %) (soit 94 %) (soit 100 %) BPA concentration in receipts (% m/m) Moyenne 1,33 % 1,33 % 1,9 % 1,14 % 1,58 % 1,24 % 1,70 % 0,0211 %2 1,46 % Min – Max 0,8–1,9 % 0,8–1,7 % 0,8–2,8 % 0,87-1,70 % 0,58-3,2 % 0,3–1,5 % 0,9–2,2 % <10-7–1,4 % 0,9-2,1 % LD / LQ LD : 0,01% LQ : 0,00005% non précisé LD = 0,00005% LD = 0,00005% LD : 0,09% LD : 0,005% LQ : 10-7% LQ = 0,000001% LQ : 0,02% LQ : 0,26% Analytical LC-MS/MS HPLC/fluo HPLC/ CoulArray HPLC/GC/MS - GC/FID GC/MS LC/MS-MS GC-ECNI/MS method Other bisphenols BPS - BPB, BPS, BPF BPS - - - - - searched 10

Handling of thermal receipts Cashier scenario – Pregnant women F =Percutaneous absorption flow, D= duration of exposure, S= surface in contact with the paper, BW=body weight F (µg.cm-2.h-1) x D (h.d-1) x S (cm2) Internal dose (µg.kgbw-1.d-1) = BW (kg) Internal Dose (µg/kgBW/d) DI TICKET THERMIQUE TRAVAILLEURS FEMMES ENCEINTES 0,014 0,434 Minimum 0.01 95,0% 5,0% 0,06 P5 0.05 Probability of occurrence P25 0.11 0,05 P95 P50 0.20 0,04 P75 0.29 0,03 P90 0.38 0,02 P95 0.43 0,01 Maximum 0.71 Mean 0.21 0,00 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 Internal dose (µg/kgBW/j) 11

Effect on the femal Effect on brain and ITV = 0.005 µg/kg/j reproductive ITV = 0.01 µg/kg/j behaviour system DI TICKET THERMIQUE TRAVAILLEURS FEMMES ENCEINTES DI TICKET THERMIQUE TRAVAILLEURS FEMMES ENCEINTES 0,014 0,434 0,014 0,434 95,0% 5,0% 95,0% 5,0% 0,06 0,06 P95 P95 0,05 0,05 0,04 0,04 0,03 0,03 0,02 0,02 0,01 0,01 0,00 0,00 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 Level of 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 confidence : Effect on limited Effet on mammary metabolism and ITV = 0.009 µg/kg/j ITV = 0.0025 µg/kg/j gland obesity DI TICKET THERMIQUE TRAVAILLEURS FEMMES ENCEINTES DI TICKET THERMIQUE TRAVAILLEURS FEMMES ENCEINTES 0,014 0,434 0,014 0,434 95,0% 5,0% 95,0% 5,0% 0,06 0,06 P95 P95 0,05 0,05 0,04 0,04 0,03 0,03 0,02 0,02 0,01 0,01 0,00 0,00 12 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8

Conclusions There are risk situations for the unborn child associated with exposure to BPA during pregnancy . Risks relate to the mammary gland and may be characterized by an increase in the number of undifferentiated epithelial structures associated with an increased susceptibility of the mammary gland to tumour transfomation. The risks potentially affect children of both sexes. Given the uncertainties associated with the RA, the conf onfidenc dence lev evel el has as been een • described des ed as as moder oderate by the experts . The aggregate assessment taking into account the different exposures showed the • pr predom edomina nanc nce of of di diet etar ary ex expos osur ure co comp mpare red to to ot other her rout utes es. Nevertheless the study of particular exposure scenarios during pregnancy identified spec pecific ri risk sk situat ations ons as assoc ociat ated wit with th the han handl dling ng of of ther hermal pap paper er and also with the drinking of water from refillable polycarbonate containers