Biomonitoring Summary
Bisphenol A
CAS No. 80-05-7
General Information
Bisphenol A is a phenolic chemical which has been used for over 50 years in the manufacture of polycarbonate plastics and epoxy resins; in thermal paper production; and as a polymerization inhibitor in the formation of some polyvinyl chloride plastics. Polycarbonates are used to make products such as compact discs, automobile parts, baby bottles, plastic dinnerware, eyeglass lenses, toys, and impact-resistant safety equipment. Epoxy resins containing bisphenol A are used in protective linings of some canned food containers, wine vat linings, epoxy resin-based paints, floorings, and some dental composites. In recent years, about 5-6 billion pounds of bisphenol were produced annually worldwide. Bisphenol A may enter the environment from industrial sources or from product leaching, disposal, and use. In 1999-2000, bisphenol A was detected in 41.2% of 139 U.S. streams in 30 states (Kolpin et al., 2002). Bisphenol A can be biodegraded and does not bioaccumulate significantly in aquatic organisms. Some invertebrates may be sensitive and show reproductive effects (European Commission, 2003).
General population exposure to bisphenol A may occur through ingestion of foods in contact with bisphenol A containing materials. For small children, hand-to-mouth and direct oral contact with materials containing bisphenol A are possible. Exposure from indoor air is a small component of total exposure estimates (Wilson et al., 2007. In animal and human studies, bisphenol A is well absorbed orally. In humans, little free bisphenol A circulates after oral absorption due to the high degree of glucuronidation by the liver. The glucuronidated bisphenol A is excreted in the urine within 24 hours with no evidence of accumulation (Volkel et al., 2002).
Human health effects from bisphenol-A at low environmental doses or at biomonitored levels from low environmental exposures are unknown. Occupational exposure of epoxy workers to bisphenol A dust may produce eye irritation and skin sensitization. In animal studies, bisphenol A has low acute toxicity. It is not considered a teratogen (Kim et al., 2001). Bisphenol A is rated as weakly estrogenic (Matthews et al., 2001). Some reproductive or developmental changes are observed at high doses in standard experimental animal studies (e.g., delayed vaginal opening and preputial separation) (Ema et al., 2001; Tyl et al., 2002; NTP-CERHR, 2008). Reproductive and neurodevelopmental effects of bisphenol A at low doses in animals, including environmental doses potentially relevant to humans, have been the subject of ongoing scientific reviews and study (European Commission, 2002, 2010; Gray et al., 2004; NTP, 2001; NTP-CERHR, 2007 and 2008; vom Saal and Hughes, 2005 Welshons et al., 2006; Witorsch, 2002). Examples of recent animal studies which suggest possible low dose effects include altered development of the fetal prostate and mammary gland, inhibition of postnatal testosterone production, and changes in neurodevelopment (Akingbemi et al., 2004; Leranth et al., 2008; NTP-CERHR, 2007; Timms et al., 2005).
Bisphenol A is not considered mutagenic and is unlikely to be a carcinogen, although it may form DNA adducts in vitro and inhibit mitotic spindle activity (Haighton et al., 2002). IARC and NTP do not have ratings for bisphenol A with respect to human carcinogenicity. The epoxy resin oligomer, bisphenol A diglycidyl ether, has limited evidence of animal carcinogenicity and is not classifiable as a human carcinogen by IARC.
Biomonitoring Information
Urinary levels of bisphenol A include both conjugated and unconjugated forms and reflect recent exposure to the chemical. In the participants of NHANES 2003-2004, prevalent exposure to bisphenol A in the U.S. population was demonstrated with children, females, and lower income strata having slightly higher urinary levels (Calafat et al., 2008). This study confirmed levels seen in an earlier smaller sample of 394 U.S. residents (Calafat et al., 2005), and slightly higher levels in children and non-Hispanic blacks is also apparent in NHANES 2005-2010 (CDC, 2012). Several previous small studies in Japanese pregnant women, Japanese university students, and Korean residents have found mean urinary bisphenol A levels to be similar or up to several times higher than those in the U.S. representative NHANES 2003-2004 subsample (Fujimaki et al., 2004; Kim et al., 2003; Ouchi and Watanabe, 2002), although one study of 73 Koreans found levels that averaged seven times higher than median levels in the NHANES 2003-2004 subsample (Yang et al., 2003; Calafat et al., 2008). Applications of certain dental sealants were shown to increase urinary levels of bisphenol A for 24 hours (Joskow et al., 2006). Hanaoka et al. (2002) studied workers with exposure to bisphenol A diglycidyl ether and found mean urinary levels of bisphenol A about double that of unexposed workers.
Finding a measurable amount of bisphenol A in the urine does not imply that the levels of bisphenol A cause an adverse health effect. Biomonitoring studies on levels of bisphenol A provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of bisphenol A than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.
References
Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, and Hardy MP. Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology 2004;145:592-603.
Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham LL. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 2005;113(4):391-395.
Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Perspect 2008;116(1):39-44.
Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, 2012. [online] Available at URL: https://www.cdc.gov/exposurereport/. 10/16/12
Ema M, Fujii S, Furukawa M, Kiguchi M, Ikka T, Harazono A. Rat two-generation reproductive toxicity study of bisphenol A. Reprod Toxicol 2001; 5: 505-523.
European Commission. Bisphenol A. Human Health. Directorate-General Health and Consumer Protection.Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE). May 22, 2002. Brussels, Belgium. Available at URL: http://ec.europa.eu/health/ph_risk/committees/sct/documents/out156_en.pdf. 10/16/12
European Commission. European Union Risk Assessment Report. Human health addendum of April 2008. 4,4'-Isopropylidenediphenol (Bisphenol-A) Part 2 Human Health. Joint Research Centre Institute of Health and Consumer Protection. 2010. Ispra, Italy. Available at URL: http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/15069/1/lbna24589enn.pdf. 10/16/12
Fujimaki K, Arakawa C, Yoshinaga J, Watanabe C, Serizawa S, Imai H, et al. Estimation of intake level of bisphenol A in Japanese pregnant women based on measurement of urinary excretion level of the metabolite. Nippon Eiseigaku Zasshi 2004;59(4):403-408.
Gray GM, Cohen JT, Cunha G, Hughes C, McConnell EE, Rhomberg et al. Weight of the evidence evaluation of low-dose reproductive and developmental effects of bisphenol A. Hum Ecol Risk Assess 2004;10:875-921.
Haighton LA, Hlywka JJ, Doull J, Kroes R, Lynch BS, Munro IC. An evaluation of the possible carcinogenicity of bisphenol A to humans. Regul Toxicol Pharmacol 2002;35(2 Pt 1):238-254.
Hanaoka T, Kawamura N, Hara K, Tsugane S. Urinary bisphenol A and plasma hormone concentrations in male workers exposed to bisphenol A diglycidyl ether and mixed organic solvents. Occup Environ Med 2002;59(9):625-628.
Joskow R, Barr DB, Barr JR, Calafat AM, Needham LL, Rubin C. Exposure to bisphenol A from bis-glycidyl dimethacrylate-based dental sealants. J Am Dent Assoc 2006;137(3):353-362.
Kim JC, Shin HC, Cha SW, Koh WS, Chung MK, Han SS. Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy. Life Sci 2001;69(22):2611-2625.
Kim YH, Kim CS, Park S, Han SY, Pyo MY, Yang M. Gender differences in the levels of bisphenol A metabolites in urine. Biochem Biophys Res Commun 2003;312(2):441-448.
Kolpin DW, Furlong ET, Meyer MT, Thurman EM, Zaugg SD, Barber LB, et al. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance. Environ Sci Technol 2002;36(6):1202-1211.
Leranth, C., Szigeti-Buck, K., MacLusky, N.J., and Hajszan, T. Bisphenol A prevents the synaptogenic response to testosterone in the brain of adult male rats. Endocrinology 2008;149:988-994.
Matthews JB, Twomey K, Zacharewski TR. In vitro and in vivo interactions of bisphenol A and its metabolite, bisphenol A glucuronide, with estrogen receptors alpha and beta. Chem Res Toxicol 2001;14(2):149-157.
National Toxicology Program Center for the Evaluation of Risks to Human Production (NTP-CERHR). NTP-CERHR Expert Panel Report on Reproductive and Developmental Toxicity of Bisphenol A. November 26, 2007. Available at URL: https://ntp.niehs.nih.gov/ntp/ohat/bisphenol/BPAFinalEPVF112607.pdf. 11/19/12
National Toxicology Program Health Assessment and Translation (formerly Center for the Evaluation of Risks to Human Production, NTP-CERHR). NTP-CERHR Panel Report on Reproductive and Developmental Toxicity of Bisphenol A. September, 2008. Available at URL: https://ntp.niehs.nih.gov/?objectid=49C35E83-C0BC-4D5F-4AF7273D67E03195. 10/16/12
National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review (NTP). August 2001. National Toxicology Program, U.S. Department of Health and Human Services. National Institute of Environmental Health Sciences, National Institutes of Health. Research Triangle Park, NC. Available at URL: https://ntp.niehs.nih.gov/ntp/htdocs/liason/LowDosePeerFinalRpt.pdf. 10/16/12
Ouchi K, Watanabe S. Measurement of bisphenol A in human urine using liquid chromatography with multi-channel coulometric electrochemical detection. J Chromatogr B Analyt Technol Biomed Life Sci 2002;780(2):365-370.
Timms BG, Howdeshell KL, Barton L, Bradley S, Richter CA, vom Saal FS. Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. Proc Natl Acad Sci USA 2005;102(19):7014-7019.
Tyl RW, Myers CB, Marr MC, Thomas BF, Keimowitz AR, Brine DR, et al. Three-generation reproductive toxicity study of dietary bisphenol A in CD Sprague-Dawley rats. Toxicol Sci 2002;68(1):121-146.
Volkel W, Colnot T, Csanady GA, Filser JG, Dekant W. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chem Res Toxicol 2002;15:1281-1287.
Vom Saal FS, Hughes C. An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 2005;113(8):926-33.
Welshons WV, Nagel SC, vom Saal FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology 2006;147(6 Suppl):S56-69.
Wilson NK, Chuang JC, Morgan MK, Lordo RA, Sheldon LS. An observational study of the potential exposures of preschool children to pentachlorophenol, bisphenol-A, and nonylphenol at home and daycare. Environ Res 2007;103(1):9-20.
Witorsch RJ. Low-dose in utero effects of xenoestrogens in mice and their relevance to humans: an analytical review of the literature. Food Chem Toxicol 2002;40(7):905-12.
Yang M, Kim SY, Lee SM, Chang SS, Kawamoto T, Jang JY, et al. Biological monitoring of bisphenol a in a Korean population. Arch Environ Contam Toxicol 2003;44(4):546-51.
