You are here: EPA Home Research Environmental Assessment IRIS IRIS Summaries

Integrated Risk Information System

Recent Additions | Contact Us Search: All EPA IRIS 

List of IRIS Substances

Search IRIS by Keyword

IRIS Summaries/Toxicological Reviews

Entire IRIS Website

Category (section) Status Last Revised

Critical Effect Experimental Doses*

view QuickView

0356

Bisphenol A.; CASRN 80-05-7

Health assessment information on a chemical substance is included in IRIS only after a comprehensive review of chronic

toxicity data by U.S. EPA health scientists from several Program Offices and the Office of Research and Development. The

summaries presented in Sections I and II represent a consensus reached in the review process. Background information

and explanations of the methods used to derive the values given in IRIS are provided in the Background Documents.

STATUS OF DATA FOR Bisphenol A.

File First On-Line 09/26/1988

Oral RfD Assessment (I.A.) on-line 07/01/1993

Inhalation RfC Assessment (I.B.) no data

Carcinogenicity Assessment (II.) no data

_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A. Reference Dose for Chronic Oral Exposure (RfD)

Substance Name — Bisphenol A.

CASRN — 80-05-7

Last Revised — 07/01/1993

The oral Reference Dose (RfD) is based on the assumption that thresholds exist for certain toxic effects such as cellular

necrosis. It is expressed in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning perhaps an

order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without

an appreciable risk of deleterious effects during a lifetime. Please refer to the Background Document for an elaboration of

these concepts. RfDs can also be derived for the noncarcinogenic health effects of substances that are also carcinogens.

Therefore, it is essential to refer to other sources of information concerning the carcinogenicity of this substance. If the

U.S. EPA has evaluated this substance for potential human carcinogenicity, a summary of that evaluation will be contained

in Section II of this file.

__I.A.1. Oral RfD Summary

UF MF RfD

Reduced mean body

weight

NOEL: None

LOAEL: 1000 ppm diet

1000 1 5E-2

mg/kg/day

Share

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

1 of 6 6/29/2011 1:43 PM
Rat Chronic Oral

Bioassay

NTP, 1982

(50 mg/kg/day)

*Conversion Factors: Assumed food consumption equivalent to 5% of body weight/day

__I.A.2. Principal and Supporting Studies (Oral RfD)

NTP (National Toxicology Program). 1982. NTP Technical report on the carcinogenesis bioassay of bisphenol A (CAS No.

80-05-7) in F344 rats and B6C3F1 mice (feed study). NTP-80-35. NIH Publ. No. 82-1771.

In this 103-week dietary study, groups of 50 rats/sex were fed diets containing 0, 1000, or 2000 ppm bisphenol A. All

treated groups of rats had reduced body weights, compared with controls, evident from the 5th week of exposure. Food

consumption was also reduced, compared with controls, but this effect was not observed until the 12th week of treatment.

Reduced body weights in rats, therefore, was considered a direct adverse effect of exposure to bisphenol A.

In the same study (NTP, 1982), male mice (50/group) were fed diets containing 0, 1000, or 5000 ppm bisphenol A and

female mice (50/group) were fed 0, 5000, or 10,000 ppm bisphenol A. Male mice at 5000 ppm and female mice at 5000

and 10,000 had reduced body weights. At 1000 and 5000 ppm, there was an increase in the number of multinucleated giant

hepatocytes in male mice. This effect was not considered to be adverse, and this level is a NOAEL in mice. Assuming a food

factor for mice of 0.13, this dietary concentration corresponds to a dosage of 130 mg/kg/day. Because the LOAEL of 50

mg/kg/day in rats is less than the NOAEL of 130 mg/kg/day in mice, the NOAEL in mice cannot be chosen as a basis for the

RfD. The LOAEL of 50 mg/kg/day in rats, the lowest dosage used in either species in the chronic studies, is chosen as the

basis for a chronic oral RfD.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — The UF of 1000 includes 10 for uncertainty in the extrapolation of dose levels for animals to humans, 10 for

uncertainty in the threshold for sensitive humans, and 10 for uncertainty in the effects of duration on toxicity when

extrapolating for subchronic to chronic exposure.

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

Three subchronic oral toxicity studies of bisphenol A have been considered using dogs, rats and mice (U.S. EPA, 1984a,b,c;

NTP, 1982). The only toxic effect seen in beagle dogs fed 1000-9000 ppm bisphenol A in the diet for 90 days was an

increase in group mean liver weight in the high-dose group (U.S. EPA, 1984a). The only effect seen in 2-generation

bisphenol A feeding studies (100-9000 ppm) conducted with Charles River rats (U.S. EPA, 1984b,c) were decreases in body

weight in the F0 generation at 9000 ppm and F1 generation at greater than or equal to 1000 ppm. Rats and mice of both

sexes were fed bisphenol A (250 to 4000 ppm rats; 5000to 25,000 ppm mice) in the diet for 90 days (NTP, 1982). Doses

>1000 ppm produced decreased body weight in both sexes of rats with no alteration in food consumption. Male mice

receiving >15,000 ppm and all treated females had decreased body weight gain compared with controls. A dose-related

increase in severity of multinucleated giant hepatocytes was found in the treated male mice.

In mice, a dosage of 1250 mg/kg/day was associated with fetotoxicity and maternal toxicity, but did not cause a significant

increase in the incidence of malformations at any dose level (NTP, 1985a). In rats, dosages of less than or equal to 1280

mg/kg/day were not toxic and did not cause malformations to the fetus (NTP, 1985b).

__I.A.5. Confidence in the Oral RfD

Study — Medium

Database — High

RfD — High

Confidence in the key study is medium because this study, although well controlled and performed, failed to identify a

chronic NOAEL for reduced body weight, the critical effect, in rats, the most sensitive species. Confidence in the database is

high, however, because the subchronic studies in rats indicate that the NOAEL for reduced body weight in rats is probably

not far below the LOAEL of 1000 ppm of the diet and the uncertainty factor of 10 to estimate a NOAEL from the LOAEL is

probably conservative. The developmental toxicity of bisphenol A has been adequately investigated. Confidence in the RfD,

therefore, is high.

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

2 of 6 6/29/2011 1:43 PM
__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 1987

Other EPA Documentation — U.S. EPA, 1984a,b,c

Agency Work Group Review — 09/16/1987, 03/24/1988, 04/20/1988

Verification Date — 04/20/1988

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent

toxicology literature pertinent to the RfD for Bisphenol A. conducted in September 2002 identified one or more significant

new studies. IRIS users may request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or

(202)566-1676.

__I.A.7. EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone),

(202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

Top of page

_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Bisphenol A.

CASRN — 80-05-7

Not available at this time.

Top of page

_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Bisphenol A.

CASRN — 80-05-7

This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for

evidence of human carcinogenic potential.

Top of page

_III. [reserved]

_IV. [reserved]

_V. [reserved]

_VI. Bibliography

Substance Name — Bisphenol A.

CASRN — 80-05-7

Last Revised — 07/01/1992

_VI.A. Oral RfD References

NTP (National Toxicology Program). 1982. NTP Technical Report on the carcinogenesis bioassay of bisphenol A (CAS No.

80-05-7) in F344 rats and B6C3F1 mice (feed study). NTP-80-35. NIH Publ. No. 82-1771.

NTP (National Toxicology Program). 1985a. Teratologic evaluation of bisphenol A (CAS No. 80-05-7) administered to CD-1

mice on gestational days 6-15. NTP, NIEHS, Research Triangle Park, NC.

NTP (National Toxicology Program). 1986a. Teratologic evaluation of bisphenol A (CAS No. 80-05-7) administered to CD(R)

rats on gestational days 6-15. NTP, NIEHS, Research Triangle Park, NC.

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

3 of 6 6/29/2011 1:43 PM
Date Section Description

U.S. EPA. 1984a. Ninety-day oral toxicity study in dogs. Office of Pesticides and Toxic Substances. Fiche No. OTS0509954.

U.S. EPA. 1984b. Reproduction and ninety-day oral toxicity study in rats. Office of Pesticides and Toxic Substances. Fiche

No. OTS0509954.

U.S. EPA. 1984c. Fourteen-day range finding study in rats. Office of Pesticides and Toxic Substances. Fiche No.

OTS0509954.

U.S. EPA. 1987. Health and Environmental Effects Document on Bisphenol A. Prepared by the Office of Health and

Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and

Emergency Response, Washington, DC.

Top of page

_VI.B. Inhalation RfC References

None

Top of page

_VI.C. Carcinogenicity Assessment References

None

Top of page

_VII. Revision History

Substance Name — Bisphenol A.

CASRN — 80-05-7

09/26/1988 I.A. Oral RfD summary on-line

07/01/1992 I.A.2. Principal study clarified

07/01/1992 I.A.4. Citations clarified

07/01/1992 VI.A. Oral RfD references on-line

07/01/1993 I.A.6. Other EPA Documentation clarified

04/01/1997 III., IV.,

V.

Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were

removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA

Program Offices for this information.

12/03/2002 I.A.6. Screening-Level Literature Review Findings message has been added.

Top of page

_VIII. Synonyms

Substance Name — Bisphenol A.

CASRN — 80-05-7

Last Revised — 09/26/1988

80-05-7

bisferol A

Bishpenol A.

2,2-bis-4'-hydroxyfenylpropan

bis(4-hydroxyphenyl) dimethylmethane

2,2-bis(4-hydroxyphenyl)propane

2,2-bis(p-hydroxyphenyl)propane

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

4 of 6 6/29/2011 1:43 PM
IRIS Home

Chronic Health Hazards

for Non-Carcinogenic

Effects

Reference Dose for

Chronic Oral Exposure

(RfD)

Oral RfD Summary

Principal and

Supporting Studies

Uncertainty and

Modifying Factors

Additional

Studies/Comments

Confidence in the

Oral RfD

EPA Documentation

and Review

Reference

Concentration for

Chronic Inhalation

Exposure (RfC)

Inhalation RfC

Summary

Principal and

Supporting Studies

Uncertainty and

Modifying Factors

Additional

Studies/Comments

Confidence in the

Inhalation RfC

EPA Documentation

and Review

Carcinogenicity

Assessment for Lifetime

Exposure

Evidence for Human

Carcinogenicity

Weight-of-Evidence

Characterization

bis(4-hydroxyphenyl)propane

bisphenol

bisphenol A

Bisphenol A.

4,4'-bisphenol A

dian

4,4'-dihydroxydiphenyldimethylmethane

p,p'-dihydroxydiphenyldimethylmethane

2,2-(4,4'-dihydroxydiphenyl)propane

4,4'-dihydroxydiphenylpropane

4,4'-dihydroxydiphenyl-2,2-propane

p,p'-dihydroxydiphenylpropane

2,2-di(4-hydroxyphenyl)propane

beta-di-p-hydroxyphenylpropane

dimethyl bis(p-hydroxyphenyl)methane

dimethylmethylene-p,p'-diphenol

diphenylolpropane

2,2-di(4-phenylol)propane

4,4'-isopropylidenebisphenol

p,p'-isopropylidenebisphenol

p,p'-isopropylidenediphenol

NCI-C50635

phenol, 4,4'-dimethylmethylenediphenol, 4,4'-isopropylidenedipropane, 2,2-bis(p-hydroxyphenyl)-

Top of page

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

5 of 6 6/29/2011 1:43 PM
EPA Home Privacy and Security Notice Contact Us

http://www.epa.gov/ncea/iris/subst/0356.htm

Print As-Is

Last updated on Monday, March 07, 2011

This document will now print as it appears on screen when you use the File » Print command.

Use View » Refresh to return to original state.

Human

Carcinogenicity

Data

Animal

Carcinogenicity

Data

Supporting Data for

Carcinogenicity

Quantitative Estimate

of Carcinogenic Risk

from Oral Exposure

Summary of Risk

Estimates

Dose-Response

Data

Additional

Comments

Discussion of

Confidence

Quantitative Estimate

of Carcinogenic Risk

from Inhalation

Exposure

Summary of Risk

Estimates

Dose-Response

Data

Additional

Comments

Discussion of

Confidence

EPA

Documentation,

Review and,

Contacts

Bibliography

Revision History

Synonyms

Recent Additions | Search IRIS | IRIS Home | Environmental Assessment | Research

Bisphenol A. (CASRN 80-05-7) | IRIS | US EPA http://www.epa.gov/ncea/iris/subst/0356.htm

6 of 6 6/29/2011 1:43 PM