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Bisphenol A.
CASRN 80-05-7
Contents
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 On-Line 09/26/1988
Category (section) Status Last Revised
----------------------------------------- -------- ------------
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
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Reduced mean body NOEL: None 1000 1 5E-2
weight mg/kg/day
LOAEL: 1000 ppm diet
Rat Chronic Oral (50 mg/kg/day)
Bioassay
NTP, 1982
*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 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
Data Base -- 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 data base 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.
___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
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Bisphenol A.
CASRN -- 80-05-7
Not available at this time.
_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.
_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.
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.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Bisphenol A.
CASRN -- 80-05-7
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
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
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
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'-dimethylmethylenedi-
phenol, 4,4'-isopropylidenedi-
propane, 2,2-bis(p-hydroxyphenyl)-
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0356.HTM
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