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Hazard Identification Materials for Consideration of the Female Reproductive Toxicity of Bisphenol-A

Bisphenol A (BPA) will be considered for listing at the next meeting of the Developmental and Reproductive Toxicant Identification Committee (DARTIC) scheduled for May 7, 2015 in Sacramento. At this meeting , the DARTIC will consider whether BPA "has been clearly shown through scientifically valid testing according to generally accepted principles to cause female reproductive toxicity".

BPA is being brought to the DARTIC consistent with the committee's request at its July 15, 2009 meeting to re-visit consideration of BPA if additional epidemiological or other specific types of data on reproductive and developmental toxicity became available. Substantial new epidemiological and toxicological data on BPA and female reproductive toxicity have become available since 2009. The Office of Environmental Health Hazard Assessment (OEHHA) has compiled for consideration by the DARTIC the following hazard identification materials on BPA and female reproductive toxicity.

Video of the DART meeting held on May 7, 2015.

Hazard Identification Materials on the Female Reproductive Toxicity of BPA

The following materials are being provided to the DARTIC:

The hazard identification materials provided to the DARTIC in 2009:

  1. OEHHA, "Evidence on the Developmental and Reproductive Toxicity of Bisphenol A." October 2009. This document provides an integrative review of the data available in 2009.
  2. National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR, 2008). "NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A." NTP, US Department of Health and Human Services, Research Triangle Park, NC, NIH Publication No. 08-5994.
  3. European Union (EU). "European Union (EU) Risk Assessment Report: 4,4'-isopropylidenediphenol (bisphenol-A)." Final Report, 2003
  4. EU Update of the Risk Assessment of 4,4'-Isopropylidenediphenol (Bisphenol-A), Final Human Health Draft for publication, 2008.
  5. Public comments submitted to the DARTIC in 2009 regarding possible listing of BPA.

The hazard identification materials provided to the DARTIC in 2009:

  1. OEHHA, "Evidence on the Developmental and Reproductive Toxicity of Bisphenol A." October 2009. This document provides an integrative review of the data available in 2009.
  2. National Toxicology Program - Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR, 2008). "NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A." NTP, US Department of Health and Human Services, Research Triangle Park, NC, NIH Publication No. 08-5994.
  3. European Union (EU). "European Union (EU) Risk Assessment Report: 4,4'-isopropylidenediphenol (bisphenol-A)." Final Report, 2003
  4. EU Update of the Risk Assessment of 4,4'-Isopropylidenediphenol (Bisphenol-A), Final Human Health Draft for publication, 2008.
  5. Public comments submitted to the DARTIC in 2009 regarding possible listing of BPA.

Articles and reports available to OEHHA and cited in the 2014 EHP review, OEHHA (2009), NTP-CERHR, (2008), EU (2003) and (EU 2008) that directly pertain to female reproductive toxicity are also being provided, as is a list of the articles and reports that OEHHA was unable to obtain.

Portions of Provided Documents Relevant to Female Reproductive Toxicity

To assist the committee and public, the relevant pages from the 2014 EHP review and the OEHHA, NTP, and EU documents that are directly relevant to female reproductive toxicity in mammals are identified below.

  • Bisphenol A and Reproductive Health: Update of Experimental and Human Evidence, 2007–2013 (Peretz et al., Env. Hlth. Perspect., 2014, 122(8): 775-786) [2014 EHP Review]
    • Abstract (Page 775)
    • Early oogenesis and ovarian follicle formation (Pages 776-777)
    • Steroidogenesis in females (Page 777)
    • Oocytes: quantity, quality, and fertilization (Pages 777-778)
    • Polycystic ovarian syndrome (Page 778)
    • Oviduct (Page 778)
    • Uterine morphology (Page 778)
    • Uterine endometrium (Pages 778-779)
    • Uterine receptivity and implantation (Page 779)
    • Placenta (Page 779)
    • Pregnancy outcomes (Pages 779-780)
    • Puberty and sexual receptivity (Pages 782-783)
    • Sexual dysfunction (Page 783)
    • Conclusions (Page 783)
  • Evidence on the Developmental and Reproductive Toxicity of Bisphenol A (OEHHA, 2009)
    • Executive Summary (Pages 11-12)
    • Female reproductive studies in humans (Pages 65-67)
    • Female reproductive studies in laboratory rodents (Pages 68-119)
    • Uterine weight effects (Page 68)
    • Uterine cell morphology (Page 69)
    • Uterine protein expression (Page 70)
    • Effects on gravid uteri (Page 71)
    • Long-term uterine effects of neonatal exposure (Page 71)
    • Effects on the ovary (Pages 82-84)
    • Effects on the ovarian follicles and oocytes (Pages 84)
    • Effects on the estrous cycle (Pages 93-98)
    • Altered estrous cycle patterns and lengths (Pages 93-94)
    • Alteration of estrous cycle onset (Pages 95-98)
    • Effects on fertility (Page 99)
    • Multi-generation studies (Pages 99-100)
    • Reproductive Assessment by Continuous Breeding (RACB) biosassay (Page 101)
    • Effects on the vagina (Pages 101-106)
    • Effects on the mammary gland (Pages 107-113)
    • Maternal behavior (Page 118)
    • Summary and human health relevance (Pages 119-120)
    • Appendix 1: Female Reproductive Toxicity Studies (Pages A1-7 – A1-16)
  • NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A (2008) [Attachment to OEHHA, 2009]
    • Can Bisphenol A Affect Human Development or Reproduction? (Pages 6-9)
    • Human studies (Page 15)
    • Reproductive studies in animals (developmental pertaining to female reproductive toxicity endpoints) (Pages 16-17)
    • Mammary gland (Pages 21-24)
    • Puberty and Sexual Maturation (Pages 26-29)
    • Other Effects Considered (Pages 29-30)
    • Evaluation of reproductive organ data (BDR Pages 239, 241, 245-246)
    • Rat - oral exposure postnatally with or without prenatal exposure. Reproductive studies. (BDR Pages 247-252, 254-255, 258-260, 263-264, 268-269, 271-272, 273-274, 278-279, 281-283, 285-286, 288, 292-293, 294-295, 299)
    • Mouse - parenteral exposure postnatally with or without prenatal exposure. Female reproductive endpoints. (BDR Pages 303-305)
    • Sheep (BDR Pages 307-308)
    • Development pertaining to reproductive toxicity (BDR Pages 321-325)
    • Reproductive system development (BDR Pages 328-339)
    • Reproductive toxicity data: human female (BDR Pages 330-332)
    • Reproductive toxicity: female experimental animals (BDR Pages 333-338)
    • Reproductive toxicity: male and female (BDR Pages 357-371, 374-378)
    • Utility of reproductive toxicity data: (BDR Pages 378-379)
    • Summary of reproductive toxicity data (BDR Pages 379-381)
    • Summaries, Conclusions, and Critical Data Needs: Reproductive Toxicity (BDR Page 381)
  • EU Risk Assessment Report: 4,4'-isopropylidenediphenol (bisphenol-A). Final Report (2003) [Attachment to OEHHA, 2009]
    • In the section "Toxicity to Reproduction"
      • Studies investigating endocrine modulating activity: in vitro systems (Pages 197-198, 201-212)
      • Effects on fertility (Pages 212-220)
      • Effects on development pertaining to reproduction (Pages 223-226)
      • Summary of toxicity to reproduction (Pages 231-233)
  • EU "Updated European Risk Assessment Report 4,4'-Isopropylidenediphenol (bisphenol-A). Environment Addendum of February 2008 (to be read in conjunction with published EU RAR of Bisphenol A, 2003)." [Attachment to OEHHA, 2009]
    • In the section "Reproductive Toxicity"
      • Summary of original risk assessment report (Pages 84-86)
      • Updated information (Pages 86-90, 91-92, 96-97, 100, 103-104)
      • Developmental effects on female reproductive tract expressed in old-age (Pages 120-121)
      • Human case control study (Page 121)
      • Impact of new information and summary of reproductive toxicity (Pages 122, 127-129)

Link to Public Comments

Public comments on the Hazard Identification Materials

US Food and Drug Administration - Update on Bisphenol A (BPA) for Use in Food Contact Applications http://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm064437.htm European Food Safety Authority - Scientific Opinion on the Risks to Public Health Related to the Presence of Bisphenol A (BPA) in Foodstuffs http://www.efsa.europa.eu/en/efsajournal/pub/3978

Thursday, April 23, 2015

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