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Benomyl
CASRN 17804-35-2
Contents
0011
Benomyl; CASRN 17804-35-2
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 Benomyl
File On-Line 01/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 03/01/1989
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 -- Benomyl
CASRN -- 17804-35-2
Last Revised -- 03/01/1989
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
-------------------- ----------------------- ----- --- ---------
Decreased pup NOEL: 100 ppm diet 100 1 5E-2
weanling weights (5 mg/kg/day) mg/kg/day
3-Generation LEL: 500 ppm
Reproduction Rat (25 mg/kg/day)
Study
du Pont, 1968a
*Conversion Factors: l ppm = 0.05 mg/kg/day (assumed rat food consumption)
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
E.I. duPont de Nemours and Co. 1968a. MRID No. 00066773. Available from
EPA. Write to FOI, EPA, Washington DC. 20460.
Benomyl, 50 or 70% wettable powder (dose based on % active ingredient), was
administered in the diet at 0, 100, 500, and 2500 ppm (0, 5, 25, and 125
mg/kg/day) to male and female ChR-CD rats for 3 generations (7 litters). Six
males and females were mated for the first generation, 12 males and females
for the second generation, and 20 males and females for the third generation.
Histology was performed on F3bn weanlings. F3c pups were used for a post
weaning growth curve study. No treatment-related effects were seen with the
exception of pup weanling weights in F2b, F3b, and F3c litters at 500 and 2500
ppm as compared with control values. The NOEL was 100 ppm (5 mg/kg/day) and
the LEL, based on decreased pup weanling weights, was 500 ppm (25 mg/kg/day).
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- A UF of 100 includes uncertainties in extrapolation from laboratory
animals to humans. The extrapolation from the teratology data was considered
to be sufficiently covered by this UF, since the NOEL for teratogenic effects
is 30 mg/kg/day, that is, 6 times higher than the NOEL of 5 mg/kg/day used to
establish the RfD. Thus, there is an overall 600-fold margin between the
teratogenic NOEL and the RfD.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Data Considered for Establishing the RfD
1) 3-Generation Reproduction - rat: Principal study - see previous
description; core grade minimum
2) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=2500 ppm (125 mg/kg/day)
(HDT); core grade minimum (E.I. du Pont de Nemours and Co., 1969)
3) 2-Year Feeding - dog: NOEL=500 ppm (12.5 mg/kg/day); LEL=2500 ppm (62.5
mg/kg/day) (biochemical alterations, hepatic cirrhosis, decreased weight gain
and lower food consumption); core grade minimum (E.I. du Pont de Nemours and
Co., 1970)
4) Teratology - rat: NOEL=30 mg/kg/day; LEL=62.5 mg/kg/day (microphthalmia);
core grade minimum (E.I. du Pont de Nemours and Co., 1982)
5) Teratology - rat: Fetotoxic NOEL=30 mg/kg/day; Fetotoxic LEL=62.5
mg/kg/day (decreased fetal weight); Maternal NOEL=125 mg/kg/day (HDT); core
grade minimum (E.I. du Pont de Nemours and Co., 1980a)
6) Teratology - mouse: Teratogenic NOEL=50 mg/kg/day; Teratogenic LEL=100
mg/kg/day (supra occipital scars, subnormal vertebral centrum, supernumary
ribs, cleft palate); core grade minimum (Kavlock et al., 1982)
Other Data Reviewed:
1) Ocogenic - mice: CD-1 mice were given 0, 500, 1500, and 7500 (reduced to
5000 ppm after 37 weeks) ppm (0, 75, 225, 1125/750 mg/kg/day). High dose
males had microscopic evidence of hepatocellular and testicular (and
epididymal) degeneration; core grade minimum (E.I. du Pont de Nemours and Co.,
1980b)
2) 90-Day Feeding - rat: NOEL=500 ppm (25 mg/kg/day); LEL=2500 ppm (125
mg/kg/day) (increased relative and absolute liver weight in females and
increased SGPT values in males); core grade minimum (E.I. du Pont de Nemours
and Co., 1967)
3) 90-Day Feeding - dog: NOEL=500 ppm (12.5 mg/kg/day); LEL=2500 ppm (62.5
mg/kg/day) (depressed albumon/globulin, A/G ratio, and increased SGPT in
males); core grade minimum (E.I. du Pont de Nemours and Co., 1968b)
Data Gap(s): None
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- High
RfD -- High
The principal study is of adequate quality and is therefore given medium
confidence. Since additional studies are of adequate quality, the data base
is given high confidence. High confidence in the RfD follows.
___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 -- Pesticide Registration Standard April, 1986;
Special Review Position Document; Pesticide Registration Files
Agency Work Group Review -- 03/26/1986
Verification Date -- 03/26/1986
___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 -- Benomyl
CASRN -- 17804-35-2
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Benomyl
CASRN -- 17804-35-2
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Benomyl
CASRN -- 17804-35-2
Last Revised -- 07/01/1989
__VI.A. ORAL RfD REFERENCES
E.I. du Pont de Nemours & Company. 1967. MRID No. 00066771. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1968a. MRID No. 00066773. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1968b. MRID No. 00066785. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1969. MRID No. 00097284. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1970. MRID No. 00097305, 00097318,
00097326. Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1980a. EPA Accession No. 256575.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1980b. MRID No. 00096514. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. du Pont de Nemours & Company. 1982. MRID No. 00115674. Available from
EPA. Write to FOI, EPA, Washington D.C. 20460.
Kavlock, R.J., N. Chernoff, L.E. Gray, Jr., J.A. Gray and D. Whitehouse.
1982. Teratogenic effects of benomyl in the Wistar rat and CD-1 mouse, with
emphasis on the route of administration. Toxicol. Appl. Pharmacol. 62:
44-54.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Benomyl
CASRN -- 17804-35-2
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 I.A.5. Confidence levels revised
03/01/1989 I.A. Major text revisions
07/01/1989 VI. Bibliography on-line
01/01/1992 IV. Regulatory action updated
VIII. SYNONYMS
Substance Name -- Benomyl
CASRN -- 17804-35-2
Last Revised -- 01/31/1987
17804-35-2
ARILATE
BBC
BENLAT
BENLATE
BENLATE 50
BENLATE 50 W
Benomyl
BENOMYL 50W
2-BENZIMIDAZOLECARBAMIC ACID, 1-(BUTYLCARBAMOYL)-, METHYL ESTER
BNM
1-(BUTYLCARBAMOYL)-2-BENZIMIDAZOLECARBAMIC ACID, METHYL ESTER
1-(BUTYLCARBAMOYL)-2-BENZIMIDAZOL-METHYLCARBAMAT
CARBAMIC ACID, METHYL-, 1-(BUTYLCARBAMOYL)-2-BENZIMIDAZOLE ESTER
D 1991
DU PONT 1991
F1991
FUNDASOL
FUNDAZOL
FUNGICIDE 1991
MBC
METHYL 1-(BUTYLCARBAMOYL)-2-BENZIMIDAZOLYLCARBAMATE
1-(N-BUTYLCARBAMOYL)-2-(METHOXY-CARBOXAMIDO)-BENZIMIDAZOL
TERSAN 1991
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0011.HTM
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