Toxicological Relevance of Endocrine Disrupting Chemicals (EDCs( EDCs) ) and Pharmaceuticals in Water

Transcription

1 Toxicological Relevance of Endocrine Disrupting Chemicals (EDCs( EDCs) ) and Pharmaceuticals in Water AwwaRF Project #3085 / WRF No part of this presentation may be copied, reproduced or otherwise utilized without permission.

2 pharmaceuticals and EDCs in drinking water Source:

3 strengths and limitations of This study is this study Not meant to provide numbers for regulations Not meant to evaluate ALL pharma/edcs Not meant to evaluate mixture toxicity This study provides: Robust analytical and toxicological methodology An initial understanding using detected pharma/edc agents Additional occurrence data Toxicity assessments for key pharms/edcs This study is a beginning, and more research is needed

4 pharmaceuticals Source:

5 endocrine disruptors (EDCs) Source:

6 Source:

7 National Research Council (NRC) Health Implications of Perchlorate Ingestion. National Academy Press. Washington, DC. New Jersey Drinking Water Quality Institute (NJDWQI) Maximum Contaminant Level Recommendation for Perchlorate. New Jersey Drinking Water Quality Institute. Submitted to Commissioner B.M. Campbell, NJDEP. Newnham HH, Topliss DJ, Le Grand BA, Chosich N, Harper RW and Stockigt JR Amiodarone-induced hyperthyroidism: assessment of the predictive value of biochemical testing and response to combined therapy using propylthiouracil and potassium perchlorate. Aust N Z J Med. 18: Noonan NE Interim Assessment Guidance for Perchlorate. Memorandum. United States Environmental Protection Agency, Office of Research and Development. Washington, DC June 18. Nzengung VA, Wang C and Harvey G Plant-mediated transformation of perchlorate into chloride. Environ Sci Technol. 33: Orris GJ, Harvey GJ, Tsui DT and Eldridge JE Preliminary analyses for perchlorate in selected natural materials and their derivative products. U.S. Geological Survey Open-File Report : Tucson, AZ: U.S. Geological Survey. Parsons "Scientific and technical report for perchlorate biotransport investigation: A study of perchlorate occurrence in selected ecosystems. Interim final report." Air Force Institute for Environment, Safety and Occupational Health Risk Analysis. Brooks Air Force Base, TX, USA. Patino R, Wainscott MR, Cruz-Li EI, Balakrishnan S, 1) McMurry aggregated C, Blazer known VS and Anderson TA Effects of ammonium data perchlorate on the reproductive performance and thyroid follicle histology of zebrafish. Environ Toxicol Chem. 22: PE J., S G., T S., Rohrer JS and Pohl CA Improved method determination of trace perchlorate in ground and drinking waters by ion chromatography. J Chromatogr A. 888(1-2): Pearce EN, Leung AM, Blount BC, Bazrafshan HR, He X, Pino S, Valentin-Blasini L and Braverman L Breast milk iodine and perchlorate concentrations in lactating Boston-area women. J Clin Endocrinol Metab.: Perchlorate Study Group (PSG). n.d. Position Paper of the Perchlorate Study Group Concerning Revision of the Perchlorate Public Health Goal to Adopt Scientific Findings of the National Acadmy of Sciences. Bates Number: AFL Postel S Placental transfer of perchlorate and triiodothyronine in the guinea pig. Endocrinology. 60: Primedica Hormone, Thyroid and Neurohistological Effects of Oral (Drinking Water) Exposure to Ammonium Perchlorate in Pregnant and Lactating Rats and in Fetuses and Nursing Pups Exposed to Ammonium Perchlorate during Gestation or via Maternal Milk (Argus ). Argus Research Laboratories. Horsham, PA. Reichert LJM and de Rooy HAM Treatment of amiodarone induced hyperthyroidism with potassium perchlorate and methimazole during amiodarone treatment. British Med J. 298(6687): Research Triangle Institute (RTI) Perchlorate Peer Review Workshop Report. EPA Contract Number 68-W Prepared for Office of Solid Waste, U.S. Environmental Protection Agency, Washington, DC, by Center for Environmental Analysis, Research Triangle Institute. Research Triangle Park, NC. Richardson SD and Ternes TA Water analysis: emerging contaminants and current issues. Anal Chem. 77(12): Rickman JE LC/MS/MS measures perchlorate in ppb range. Trends in Anal Chem. 22: VIII-IX.

8 2) what was scientifically reliable. Source: -

9 3) determined the most sensitive endpoints. Source: -

10 focused the list of pharmaceuticals and EDCs Source: -

11 selection of target pharmaceuticals Prescription drugs 1 3, Potential for toxicity Most used Final candidates 4 Detection; Public interest 5 Drug groups

12 1 selection of EDCs Status as an EDC Hundreds of purported EDCs Selected data compilations screened Criteria: In vivo Relevant species Endocrine mediated effect Adverse effect 2 Occurrence & exposure Occurrence in drinking water, especially U.S. Resistance to conventional drinking water treatment Availability of method for analysis 3 Potential for toxicity Severity of effects Potency Pharmacokinetics Availability of studies suitable for risk assessment 4 5 Final candidates 13 EDCs PAC, public, scientific interest Endocrine Mode of Action

13 deriving ADIs / screening values carcinogens Response Slope factor Tumor response Dose non cancer

14 selected pharmaceuticals cancer and non cancer endpoints R R/M R R Evidence of Cancer in Rat or Mouse R/M R/M R

15 selected EDCs endocrine-mediated endpoints

16 drinking water equivalent levels (DWELs) Non Cancer Consume 2 liters of water per day 70 kg body weight ADI ( μg/ kg d) 70 kg DWEL ( μg/l) = 2 L / d Carcinogens Acceptable risk of 1 in 1,000,000 (10-6 ) and exposure for 30 years over a 70 year lifetime kg 70 yr DWEL ( μg/l) = 1 SF ( μg/kg d) 2 L / d 30 yr

17 pharmaceuticals -Max Finished Water Conc data from Dr. Snyder s Lab

18 EDCs *None directly based on endocrine-medicated effects unless otherwise indicated Based on endocrine effect Environment Protection and Heritage Council **Joint FAO/WHO Expert Committee on Food Additives -Max Finished Water Conc data 2008 from Awwa Dr. Research Snyder s Foundation. Lab ALL RIGHTS RESERVED.

19 concerns might be raised Source: -

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21 1 second in 32 years = 1 ppb Source:

22 1 pancake in stack 4 miles high = 1 ppb Source: -

23 meprobamate =.043 ppb atrazine = 1 ppb Source:

24 phenytoin: ~1800 (8 oz) glasses of water per day = ADI/Screening value Source:

25 bisphenol A: ~ 25 (8 oz) glasses of water per day = ADI/ Screening value Source:

26 bisphenol A: ~ 148,000 (8 oz) glasses of water per day = EPA RfD Source:

27 amount of water to meet ADI / screening value pharmaceuticals

28 amount of water to meet ADI /screening value EDCs

29 estrogens: human breast milk: ~ ng/ml government ADI = ng/ml Source: -

30 conclusions Pharms/EDCs are a significant public interest Pharmaceuticals and EDCs can be detected in water Based on research so far, selected pharms occur below estimated ADIs / screening values

31 contact Intertox, Inc nd Ave Suite 415 Seattle, WA USA Tel: