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Benomyl (CASRN 17804-35-2)

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Benomyl; CASRN 17804-35-2

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR Benomyl

File First 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
weanling weights

3-Generation Reproduction
Rat Study

du Pont, 1968a

NOEL: 100 ppm diet
(5 mg/kg/day)

LEL: 500 ppm
(25 mg/kg/day) 

100
1
5E-2
mg/kg/day

*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 Studies/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
Database — High
RfD — High

The principal study is of adequate quality and is therefore given medium confidence. Since additional studies are of adequate quality, the database 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

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 Benomyl 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).

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_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.

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]


_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.

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_VI.B. Inhalation RfC References

None

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_VI.C. Carcinogenicity Assessment References

None

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_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
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.

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_VIII.  Synonyms

Substance Name — Benomyl
CASRN — 17804-35-2
Last Revised — 01/31/1987

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