Chlorimuron-ethyl (CASRN 90982-32-4)
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0406
Chlorimuron-ethyl; CASRN 90982-32-4
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 Chlorimuron-ethyl
File First On-Line 11/01/1989
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 11/01/1989 |
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 — Chlorimuron-ethyl
CASRN — 90982-32-4
Last Revised — 11/01/1989
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
|
---|---|---|---|---|
Increase in WBC, 1-Year Dog Study duPont, 1985 |
NOEL: 250 ppm LEL: 1500 ppm |
300
|
1
|
2E-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. duPont de Nemours and Company, Inc. 1985. MRID No. 00149579. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Twenty-four male and 24 female beagle dogs were randomly vdistributed into four dose groups consisting of six males and six females. Each animal was given a daily allotment Purina Certified Canine Diet No 5007 (350 g) containing INF- 6025 at 0, 25, 250, or 1500 ppm (0, 0.625, 6.25, 37.5 mg/kg/day) for 1 year. Dogs were housed individually in stainless steel cages. Water was provided ad libitum.
Mortality was not affected by the test substance. Compound-related decreases were seen in RBC counts, HCT values, and Hb concentrations. Although occasional changes in RBC mass was parameters were seen in the 250 ppm group, these changes did not exhibit a dose-relationship and it was concluded that they were a function of the small sample size. In the high-dose group (1500 ppm) males, ALP activity was significantly elevated at 3, 6, 9, and 12 months. The high-dose females had significantly elevated ALP activity at 6 months and elevated WBC counts with increased neutophils and monocytes. These effects were considered compound-related. Although there were no changes in liver morphology, the increase in relative liver weight for the female high-dose group was considered compound-related, primarily because of the associated increase in ALP activities.
The NOEL for INF-6025 is 250 ppm (6.25 mg/kg/day). The LEL is 1500 ppm (37.5 mg/kg/day) based on increased mean relative liver weight in female dogs and effects on hematology [increased alkaline phosphatase (ALP) in male dogs and decreased erythrocyte (RBC) counts and other effects related to RBC mass and increased leukocyte (WBC) counts in male and female dogs].
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 100 was used to account for the inter-and intraspecies differences. An additional UF of 3 was used to account for the lack of an adequate reproduction study.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
1) 1-Year Feeding - dog: Principal study - see previous description;
2) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=250 ppm (12.5 mg/kg/day); Systemic LEL=2500 ppm (125 mg/kg/day) (lower body weights, changes in organ weights, effects on clinical chemistry and hematology parameters); core grade minimum (duPont, 1985b)
3) Teratology - rat: Maternal NOEL=30 mg/kg/day; Maternal LEL=150 mg/kg/day (decreased body weight); Developmental toxicity NOEL=30 mg/kg/day; Developmental toxicity LEL=150 mg/kg/day (increased incidence of partially ossified or unossified sternebrae); core grade minimum (duPont, 1983a)
4) Teratology - rabbit: Maternal NOEL=48.3 mg/kg/day; Maternal LEL=300 mg/kg/day (decreased weight gain); Developmental toxicity NOEL=12.8 mg/kg/day; Developmental toxicity LEL=48.3 mg/kg/day (delayed ossification); core grade minimum (duPont, 1985c)
Other Data Reviewed:
1) 18-Month Feeding (oncogenic) - mouse: Systemic NOEL=125 ppm (18.75 mg/kg/day); Systemic LEL=1250 ppm (187.5 mg/kg/day) (centrilobular hepatocellular hypertrophy at 90 days); core grade minimum (duPont, 1985d)
2) 90-Day Feeding and One-Generation Reproduction - rat: NOEL=100 ppm (5 mg/kg/day); LEL=2500 ppm (125 mg/kg/day) (body weight changes and histopathology); core grade minimum (duPont, 1983b)
3) 90-Day Feeding - dog: NOEL=100 ppm (2.5 mg/kg/day); LEL=1250 ppm (hematology changes, organ weight changes and atrophy of thymus and prostate); core grade guideline (duPont, 1983c)
4) 90-Day Feeding - mouse: NOEL=125 ppm (18.75 mg/kg/day); LEL=1250 ppm (187.5 mg/kg/day) (centrilobular hepatocellular atrophy); core grade minimum (duPont, 1984)
Data Gap(s): Rat Reproduction Study (current study to be reevaluated)
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical study is of good quality and is given a high confidence rating. Additional studies are also of good quality but an adequate reproduction study is not available, therefore the database is given a medium confidence rating. Medium 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 Files
Agency Work Group Review — 06/15/1989
Verification Date — 06/15/1989
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 Chlorimuron-ethyl conducted in September 2002 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 — Chlorimuron-ethyl
CASRN — 90982-32-4
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Chlorimuron-ethyl
CASRN — 90982-32-4
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Chlorimuron-ethyl
CASRN — 90982-32-4
Last Revised — 11/01/1989
_VI.A. Oral RfD References
E.I. duPont de Nemours and Company. 1983a. MRID No. 00131582 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1983b. MRID No. 00131581 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1983c. MRID No. 00132745 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1984. MRID No. 00143127 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1985a. MRID No. 00149579 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1985b. MRID No. 00143128 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1985c. MRID No. 00149578 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
E.I. duPont de Nemours and Company. 1985d. MRID No. 00145781 Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Chlorimuron-ethyl
CASRN — 90982-32-4
Date |
Section |
Description |
---|---|---|
11/01/1989 | I.A. | Oral RfD summary on-line |
11/01/1989 | VI. | Bibliography on-line |
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. |
_VIII. Synonyms
Substance Name — Chlorimuron-ethyl
CASRN — 90982-32-4
Last Revised — 11/01/1989
- 90982-32-4
- BENZOIC ACID, 2-(((((4-CHLORO-6-METHOXY-2-PYRIMIDINYL)AMINO)CARBONYL)AMINO)SULFONYL)-, ETHYL ESTER
- CASWELL NO. 193B
- CHLORIMURON ETHYL ESTER
- DPX-F 6025
- EPA PESTICIDE CHEMICAL CODE 128901
- ETHYL 2-(((((4-CHLORO-6-METHOXY-2-PYRIMIDINYL)AMINO)CARBONYL)AMINO)SULFONYL) BENZOATE
- ETHYL 2-(((4-CHLORO-6-METHOXYPYRIMIDINE-2-YL)AMINOCARBONYL)AMINOSULFONYL)BENZOATE