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n-Butanol
CASRN 71-36-3
Contents
0140
n-Butanol; CASRN 71-36-3
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 n-Butanol
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 09/01/1990
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 03/01/1991
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- n-Butanol
CASRN -- 71-36-3
Last Revised -- 09/01/1990
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
-------------------- ----------------------- ----- --- ---------
Hypoactivity and NOAEL: 125 mg/kg/day 1000 1 1E-1
ataxia mg/kg/day
LOAEL: 500 mg/kg/day
Rat Oral Subchronic
Study
U.S. EPA, 1986
*Conversion Factors: none
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
U.S. EPA. 1986. Butanol: Rat oral subchronic toxicity study. Office of
Solid Waste, Washington, DC.
Four groups of male and female rats (30/sex/group) were dosed daily by gavage
with 0, 30, 125 and 500 mg/kg/day of butanol for 13 weeks. Six weeks after
the initiation of dosing, an interim sacrifice of 10 rats/sex was performed to
evaluate clinical, biochemical and gross morphological changes. The remaining
animals continued in the experiment until the day of the final sacrifice (day
92 or 93). Data generated from this study on body and organ weight changes,
food consumption, moribundity, mortality, and ophthalmological, gross, and
histopathologic examinations did not show any dose-related differences between
control and treated animals. Slight but significant reductions in some
hematologic parameters were observed in the mid- and high-dosed females at the
interim, but not at final sacrifice. This effect was considered to be
transitory rather than adverse. Ataxia and hypoactivity were consistently
observed in high-dosed (500 mg/kg/day) males and females during the final 6
weeks of the dosing period. Thus, the 125 mg/kg/day dose of butanol is
considered a NOAEL for central nervous system effects in rats. By application
of an uncertainty factor of 1000, an RfD of 0.1 mg/kg/day or 9 mg/day for a 70
kg-person is derived.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 1000 was applied: 10 for intraspecies
variability, 10 for interspecies extrapolation, and 10 for expanding
subchronic to long-term exposure.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Sterner et al. (1949) reported that occupational exposure to 100 ppm (300
mg/cu.m) butanol had no impact on workers' health. This 10-year study
included hematological evaluations, test of liver function, urine analysis,
chest X-rays, ophthalmological examinations, and comparison of absenteeism
among butanol-exposed men vs. all men in the plant. Details of the
experimental protocol of this study were not available for risk analysis.
Several other human inhalation studies have reported irritations to eyes,
nose, and throat, and mild headaches, at concentrations of 50 ppm (150
mg/cu.m) or higher; however, these effects were transitory in nature. An
abstract of a rat inhalation study (4-month exposure) suggested a NOAEL of 0.8
mg/cu.m for reversible blood cholinesterase activity and increased thyroid
activity.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- High
Data Base -- Low
RfD -- Low
The oral subchronic study provided more than adequate toxicologic endpoints
based on a very well-designed experimental protocol; therefore, a high
confidence is recommended. The data base does not provide pertinent
information on oral chronic or reproductive studies; therefore, a low
confidence is recommended. A low to medium confidence is recommended for the
RfD.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- U.S. EPA, 1986
Agency Work Group Review -- 05/14/1986
Verification Date -- 05/14/1986
___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 -- n-Butanol
CASRN -- 71-36-3
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- n-Butanol
CASRN -- 71-36-3
Last Revised -- 03/01/1991
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- D; not classifiable as to human carcinogenicity
Basis -- Based on no human and no animal cancer data.
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
None.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
1-Butanol was negative in reverse mutation and DNA damage tests in
Salmonella typhimurium (McCann et al., 1975; Connor et al., 1985; Nakamura et
al., 1987), but weakly positive for inhibition of DNA synthesis in Escherichia
coli (Yoshiyama et al., 1973). Negative results were reported for sister
chromatid exchanges in chick embryo and Chinese hamster cells and for
micronucleus formation in Chinese hamster cells (Bloom, 1982; Obe and Ristowe,
1977; Lasne et al., 1984). 1-Butanol induced spindle disturbances in Chinese
hamster V79 lung cells (Onfelt, 1987).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
None.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
None.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1989
The 1989 Health and Environmental Effects Document for 1-Butanol has received
Agency and external peer review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 12/06/1990
Verification Date -- 12/06/1990
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
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).
_VI. BIBLIOGRAPHY
Substance Name -- n-Butanol
CASRN -- 71-36-3
Last Revised -- 03/01/1991
__VI.A. ORAL RfD REFERENCES
Sterner, J.H., H.C. Crouch, H.F. Brockmyre and M. Cusak. 1949. A ten-year
study of butyl alcohol exposure. Am. Ind. Hyg. Assoc. 10(3): 53-59.
U.S. EPA. 1986. Butanol: Rat oral subchronic toxicity study. Office of
Solid Waste, Washington, DC.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Bloom, S.E. 1982. 6. Detection of sister chromatid exchanges in vivo using
avian embryos. In: Cytogen. Assays Environ. Mutagens. p. 137-159.
Connor, T.H., J.C. Theiss, H.A. Hanna et al. 1985. Genotoxicity of organic
chemicals frequently found in the air of mobile homes. Toxicol. Lett. 25(1):
33-40.
Lasne, C., Z.W. Gu, W. Venegas and I. Chouroulinkov. 1984. The in vitro
micronucleus assay for detection of cytogenetic effects induced by mutagen-
carcinogens: Comparison with the in vitro sister-chromatid exchange assay.
Mutat. Res. 130(4): 273-282.
McCann, J., E. Choi, E. Yamasaki and B.N. Ames. 1975. Detection of
carcinogens as mutagens in the Salmonella/microsome test: Assay of 300
chemicals. Proc. Natl. Acad. Sci. USA. 72(12): 5135-5139.
Nakamura, S., Y. Oda, T. Shimada et al. 1987. SOS-inducing activity of
chemical carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002:
Examination with 151 chemicals. Mutat. Res. 192(4): 239-246.
Obe, G. and H. Ristow. 1977. Acetaldehyde, but not ethanol, induces sister
chromatid exchanges in Chinese hamster cells in vitro. Mutat. Res. 56(2):
211-213.
Onfelt, A. 1987. Spindle disturbances in mammalian cells. III. Toxicity, c-
mitosis and aneuploidy with 22 different compounds. Specific and unspecific
mechanisms. Mutat. Res. 182(3): 135-154.
U.S. EPA. 1989. Health and Environmental Effects Document for 1-Butanol.
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.
Yoshiyama, Y., K. Nagai, H. Some and G. Tamura. 1973. Selective inhibition
by pantoyl lactone and butyl alcohol of the initiation of DNA replication in
E. coli. Agric. Biol. Chem. 37(6): 1317-1320.
_VII. REVISION HISTORY
Substance Name -- n-Butanol
CASRN -- 71-36-3
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 I.A.5. Confidence levels revised
09/01/1990 I.A.4. Citation spelling corrected from Staner to Sterner
09/01/1990 VI. Bibliography on-line
01/01/1991 II. Carcinogen assessment now under review
03/01/1991 II. Carcinogenicity assessment on-line
03/01/1991 VI.C. Carcinogenicity references added
01/01/1992 I.A.7. Primary contact changed
01/01/1992 IV. Regulatory action updated
VIII. SYNONYMS
Substance Name -- n-Butanol
CASRN -- 71-36-3
Last Revised -- 03/31/1987
71-36-3
ALCOOL BUTYLIQUE
BUTANOL
1-BUTANOL
BUTANOLEN
Butanol, n-
BUTANOLO
BUTYL ALCOHOL
n-BUTYL ALCOHOL
BUTYL HYDROXIDE
BUTYLOWY ALKOHOL
BUTYRIC ALCOHOL
CCS 203
1-HYDROXYBUTANE
METHYLOLPROPANE
NA 1120
PROPYLCARBINOL
PROPYLMETHANOL
RCRA WASTE NUMBER U031
UN 1120
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0140.HTM
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