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N-Nitroso-di-n-butylamine
CASRN 924-16-3
Contents
0037
N-Nitroso-di-n-butylamine; CASRN 924-16-3
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-Nitroso-di-n-butylamine
File On-Line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 07/01/1993
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- N-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- N-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- N-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
Last Revised -- 07/01/1993
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 -- B2; probable human carcinogen
Basis -- Increased incidences of several tumor types in rats, mice, and
hamsters exposed by various routes
___II.A.2. HUMAN CARCINOGENICITY DATA
Human exposure to nitrosamines results from contact with mixtures
containing these compounds (e.g., cutting oils, tobacco products). Because of
potential confounding by the other substances in these mixtures, data from
human exposure is of limited use in the evaluation of carcinogenicity of
individual nitrosamines.
___II.A.3. ANIMAL CARCINOGENICITY DATA
There is a large data base on the carcinogenicity of nitrosamines, most of
which pertains to structure-activity relationships rather than to dose-
response. Druckrey reported dibutylnitrosamine produced bladder rather than
liver tumors in rats treated by s.c. injection. Dibutylnitrosamine also
induces carcinoma of the bladder, lung, and trachea in Syrian hamsters and
stomach carcinomas in Chinese hamsters treated by gavage. Liver tumors, lung
adenomas, and forestomach carcinomas were observed in male CR mice fed this
compound in the diet.
Druckrey et al. (1967) treated BD rats with dibutylnitrosamine in dietary
concentrations providing doses of 10, 20, 37, or 75 mg/kg bw/day. Treatment
was presumably lifetime. No control data were reported. All four of the
surviving high-dose animals developed liver tumors as well as 13/16, 4/10, and
2/10 in the 37, 20, and 10 mg/kg bw/day groups. Esophageal tumors and bladder
tumors were also observed in the lower dose groups. Average time-to-tumor was
treatment dose-dependent.
Bertram and Craig (1970) exposed 50 each male and female C57Bl6 mice to
either 60 mg or 240 mg dibutylnitrosamine/L in drinking water. The treatment
solution was replaced by water for 50% of all animals in the high-dose group,
as these animals showed hematuria. The remainder of the high-dose animals and
all low-dose animals were maintained on the treatment solutions until they
became moribund or died. Squamous-cell carcinomas of the bladder were found
in 44/90 high-dose mice and 19/89 low-dose mice; they predominated in the
males. Carcinomas and papillomas of the esophagus were also found.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Dibutylnitrosamine is mutagenic for E. coli and S. typhimurium and causes
mitotic recombination in S. cerevisiae, recessive lethal mutations in D.
melanogaster and chromosome aberrations in mammalian cells. Positive
responses are dependent upon the presence of mammalian metabolic enzymes
(Montesano and Bartsch, 1976).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
___II.B.1. SUMMARY OF RISK ESTIMATES
Oral Slope Factor -- 5.4E+0 per (mg/kg)/day
Drinking Water Unit Risk -- 1.6E-4 per (ug/L)
Extrapolation Method -- Linearized multistage procedure, extra risk
Drinking Water Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- -------------
E-4 (1 in 10,000) 6E-1 ug/L
E-5 (1 in 100,000) 6E-2 ug/L
E-6 (1 in 1,000,000) 6E-3 ug/L
___II.B.2. DOSE-RESPONSE DATA (CARCINOGENICITY, ORAL EXPOSURE)
Tumor Type -- bladder and esophagus tumors
Test Animals -- Mouse/C57Bl6, males
Route -- drinking water
Reference -- Bertram and Craig, 1970
Administered Tumor
Dose (mg/L) Incidence
------------- ------------
0 not reported
60 46/47
240 45/45
___II.B.3. ADDITIONAL COMMENTS (CARCINOGENICITY, ORAL EXPOSURE)
Water consumption reported by the authors indicates that males received
doses of 7.6 and 29.1 mg/kg/day. Specific tumor incidences were not reported
for control animals. The authors stated that this strain has a very low
spontaneous tumor incidence. A slope factor of 1.2 per (mg/kg)/day for
dibutylnitrosamine was calculated from the data of Druckrey et al. (1967).
The unit risk should not be used if the water concentration exceeds 60 ug/L,
since above this concentration the unit risk may not be appropriate.
___II.B.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, ORAL EXPOSURE)
Although adequate numbers of animals were treated for their lifetime,
control data were not reported. The risk estimate above is supported by an
independent study (Druckrey et al., 1967); a slope factor of 1.9 per
(mg/kg)/day was derived from these data using a one-hit model.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
Inhalation Unit Risk -- 1.6E-3 per (ug/cu.m)
Extrapolation Method -- Linearized multistage procedure, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- ---------------
E-4 (1 in 10,000) 6E-2 ug/cu.m
E-5 (1 in 100,000) 6E-3 ug/cu.m
E-6 (1 in 1,000,000) 6E-4 ug/cu.m
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION EXPOSURE
The inhalation risk estimates were calculated from the oral exposure data
in II.B.2.
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
The unit risk should not be used if air concentrations exceed 6 ug/cu.m,
since above this concentration the unit risk may not be appropriate.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION EXPOSURE)
See II.B.4.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1980
The values in the Ambient Water Quality Criteria Document for Nitrosamines
(1980) received extensive peer and public review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 07/23/1986, 08/13/1986, 10/29/1986
Verification Date -- 10/29/1986
___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-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
Last Revised -- 03/01/1990
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Bertram, J.S. and A.W. Craig. 1970. Induction of bladder tumours in mice
with dibutylnitrosamine. Br. J. Cancer. 24: 352-359.
Druckrey, H., R. Preussmann, S. Ivankovic and D. Schmaehl. 1967.
Organotropism and carcinogenic effects of 65 different N-nitroso compounds in
BD-rats. Z. Kerbsforsch. 69(2): 103-201. (Eng. trans.)
Montesano, R. and H. Bartsch. 1976. Mutagenic and carcinogenic N-Nitroso
compounds: Possible environmental hazards. Mutat. Res. 32: 179-228.
U.S. EPA 1980. Ambient Water Quality Criteria for Nitrosamines. Prepared by
the Office of Health and Environmental Assessment, Environmental Criteria and
Assessment Office, Cincinnati, OH for the Office of Water Regulations and
Standards, Washington, DC. EPA 440/5-80-064. NTIS PB 81-117756.
_VII. REVISION HISTORY
Substance Name -- N-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
09/30/1987 IV. Regulatory Action section on-line
03/01/1988 II.A.1. Text clarified
03/01/1988 II.B.1. Number rounded off
03/01/1988 II.B.4. Confidence statement revised
03/01/1988 II.C.1. Number rounded off
03/01/1988 II.C.4. Confidence statement revised
03/01/1988 II.D.3. Secondary contact changed
02/01/1990 VI. Bibliography on-line
03/01/1990 VI.C. Druckrey et al., 1972 reference title clarified
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
01/01/1992 IV. Regulatory actions updated
07/01/1993 II.D.3. Secondary contact's phone number changed
VIII. SYNONYMS
Substance Name -- N-Nitroso-di-n-butylamine
CASRN -- 924-16-3
Primary Synonym -- Dibutylnitrosamine
Last Revised -- 01/31/1987
924-16-3
1-butanamine, N-butyl-N-nitroso-
butylamine, N-nitrosodi-
DBN: DBNA
Dibutylamine, N-nitroso
Dibutylnitrosamine
di-n-butylnitrosamine
di-n-butylnitrosamin
N-butyl-N-nitroso-1-butamine
NDBA
Nitroso-di-n-butylamine, N-
N,N-di-n-butylnitrosamine
N-nitrosobutylamine
N-Nitroso-di-n-butylamine
RCRA waste number U172
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0037.HTM
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