Methomyl (CASRN 16752-77-5)
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0069
Methomyl;
CASRN 16752-77-5
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 Methomyl
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1991 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data | 10/01/1991 |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Methomyl
CASRN — 16752-77-5
Last Revised — 03/01/1991
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 |
---|---|---|---|---|
Kidney and Spleen 2-Year Feeding Study du Pont, 1968a |
NOEL: 100 ppm LEL: 400 ppm |
100 |
1 |
2.5E-2 mg/kg/day |
*Conversion Factors -- 1 ppm = 0.025 mg/kg/day (assumed dog food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
E.I. du Pont de Nemours & Company, Inc. 1968a. MRID No. 0000709l, 00009012. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Beagle dogs (4/sex/dose) were fed methomyl in their ad libitum diets. The diets contained 0 (control), 50, l00, 400, and l000 ppm methomyl. Dose- related histopathologic changes were observed in kidney and spleen at 400 and l000 ppm and in the liver and bone marrow at l000 ppm level. The enlarged prostate gland in one animal each of the l00 and 400 ppm dose group was not considered compound-related since the effect was not dose-related and since dogs tend to show prostate enlargement with age. The NOEL for systemic effects was l00 ppm (2.5 mg/kg/day).
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — A UF of l00 was used to extrapolate animal data accounting for intra- and inter-species differences.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
The NOEL (l00 ppm) observed in the dog study is further supported by lifetime studies in rats and mice, and a reproduction study in rats. In converting ppm to mg/kg/day, the dog study yields the lowest NOEL of all species tested. The NOEL for maternal toxicity in the rabbit was 2 mg/kg/day. Although a fraction lower than the NOEL used to establish the RfD, this NOEL was not used since exposure in teratology studies is by gavage and the chronic study in dogs more closely reflects continuous dietary exposure.
Data Considered for Establishing the RfD:
- 2-Year Feeding - dog: Principal study - see discussion above; core grade minimum
- 22-Month Feeding - rat: NOEL l00 ppm (5 mg/kg/day); LEL 200 ppm (l0 mg/kg/day) (effects on spleen) (females) (du Pont, 1968b)
- 2-Year Feeding - rat: NOEL l00 ppm (5 mg/kg/day); LEL 400 ppm (l0 mg/kg/day) (ChE inhibition, growth retardation) (1981); core grade minimum (du Pont, 1981a)
- 3-Generation Reproduction - rat: NOEL l00 ppm (5 mg/kg/day); core grade minimum (du Pont, 1968c)
- Teratology - rat: No teratogenic effects at highest dose, 400 ppm; maternal toxicity at 400 ppm (du Pont, 1978)
- Teratology - rabbit: No teratogenic effects at highest dose l6 mg/kg/day; maternal toxicity at 6 mg/kg/day (death and CNS effects) (du Pont, 1983)
Data Gap(s): None
Other Data Reviewed:
- 2-Year Feeding (oncogenic) - mice: Systemic NOEL=50 ppm (7.5 mg/kg/day); Systemic LEL=11 mg/kg/day (du Pont, 1981b)
- Delayed Neurotoxicity - Hens: Not a neurotoxin - tested up to 200 mg/kg/day (du Pont, 1967)
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — High
RfD — High
The 2-year dog study used for supporting the RfD is of adequate quality, but considering the study date (1968) not entirely in compliance with today's requirements. However, the rest of the database is of very good quality and supports the finding in the dog study; therefore, confidence in the database is high. High confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Files
Agency Work Group Review — 04/22/1986
Verification Date — 04/22/1986
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 Methomyl conducted in November 2001 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to 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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Methomyl
CASRN — 16752-77-5
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Methomyl
CASRN — 16752-77-5
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Methomyl
CASRN — 16752-77-5
Last Revised — 03/01/1991
_VI.A. Oral RfD References
E.I. du Pont de Nemours & Company, Inc. 1967. MRID No. 00008827. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1968a. MRID No. 0000709l, 00009012. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1968b. MRID No. 00007092, 00009011. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1968c. MRID No. 00007093. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1978. MRID No. 00008621. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1981a. MRID No. 00078361. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1981b. MRID No. 00078423. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
E.I. du Pont de Nemours & Company, Inc. 1983. MRID No. 00131257. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Methomyl
CASRN — 16752-77-5
Date |
Section |
Description |
---|---|---|
03/31/1987 | IV. | Regulatory Action section on-line |
12/01/1988 | I.A.4. | Core grades added to studies 1, 3 and 4 |
03/01/1991 | I.A.4. | Citations added |
03/01/1991 | III.A. | Health Advisory on-line |
03/01/1991 | VI. | Bibliography on-line |
10/01/1991 | II. | Carcinogenicity assessment now under review |
01/01/1992 | IV. | Regulatory actions updated |
08/01/1995 | II. | EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995. |
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. |
01/09/2002 | I.A., II. | This chemical is being reassessed under the IRIS Program. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
02/09/2004 | I.A., II. | This chemical is no longer being reassessed under the IRIS Program. See Federal Register February 9, 2004 (Volume 69, Number 26). |
_VIII. Synonyms
Substance Name — Methomyl
CASRN — 16752-77-5
Last Revised — 01/31/1987
- 16752-77-5
- ACETIMIDIC ACID, N-((METHYLCARBAMOYL)OXY)THIO-,METHYL ESTER
- ACETIMIDIC ACID, THIO-N-((METHYLCARBAMOYL)OXY)-,METHYL ESTER
- ACETIMIDOTHIOIC ACID, METHYL-, N-(METHYLCARBAMOYL) ESTER
- DUPONT 1179
- ENT 27,341
- ETHANIMIDOTHIOIC ACID, N-(((METHYLAMINO)CARBONYL)OXY)-, METHYL ESTER
- IN 1179
- LANNATE
- LANNATE L
- MESOMILE
- Methomyl
- METHYL N-((METHYLAMINO)CARBONYL)OXY)ETHANIMIDO)THIOATE
- 2-METHYLTHIO-ACETALDEHYD-O-(METHYLCARBAMOYL)-OXIM
- 2-METHYLTHIO-PROPIONALDEHYD-O-(METHYLCARBAMOYL)-OXIM
- METOMIL
- N-(((METHYLAMINO)CARBONYL)OXY)ETHANIMIDOTHIOIC ACID METHYL ESTER
- NU-BAIT II
- NUDRIN
- RCRA WASTE NUMBER P066
- SD 14999
- 3-THIABUTAN-2-ONE, O-(METHYLCARBAMOYL)OXIME
- WL 18236