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Chlorsulfuron (CASRN 64902-72-3)

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Chlorsulfuron; CASRN 64902-72-3

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 Chlorsulfuron

File First On-Line 01/31/1987

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) on-line 01/01/1990
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 — Chlorsulfuron
CASRN — 64902-72-3
Last Revised — 01/01/1990

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 body weight

2-Year Rat Study
Oral Exposure (diet)

du Pont, 1980a

NOEL: 100 ppm
(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. du Pont de Nemours & Company, Inc. 1980a. MRID No. 00031419, 00086003. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Three hundred sixty-eight male and 371 female CD rats were received from Charles River Breeding Laboratories. Following a 12-day pretest, 320 rats of each sex were divided into four groups of 80 males and 80 females and housed in pairs. Groups were fed diets containing 0, 100, 500, or 2500 ppm chlorsulfuron for two years. All rats were examined at least once daily during the first 14 weeks of the study and at least twice daily after that for abnormal behavior and clinical signs of toxicity. Three, 6, 12, 18, and 24 months after initiation of the study, 10 rats from each of the study groups were subjected to clinical chemistry, hematologic and urine analytical examinations. The observed results included a mild to moderate reduction in mean body weights and weight gains in male rats fed 500 ppm or 2500 ppm chlorsulfuron.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — A composite 100-fold UF has been used to compensate for both the interspecies differences in extrapolating to humans, and the expected intrahuman variability to the toxicity of this chemical.

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

Data Considered for Establishing the RfD

  1. 2-Year Feeding (oncogenic) - rat: Principal Study - see discussion above; core grade guideline
  2. 6-Month Feeding - dog: Systemic NOEL=2500 ppm (62.5 mg/kg/day) (HDT); core grade minimum (du Pont, 1980b)
  3. 3-Generation Reproduction - rat: Reproductive NOEL=500 ppm (25 mg/kg/day); Reproductive LEL=2500 ppm (125 mg/kg/day) (decreased fertility indices); Maternal NOEL=500 ppm; Maternal LEL=2500 ppm (decreased mean body weight); core grade guideline (du Pont, 1980c)
  4. Teratology - rat: Teratogenic NOEL=2500 ppm (125 mg/kg/day) (HDT); Maternal NOEL=2500 ppm; Fetotoxic NOEL=2500 ppm; core grade minimum (du Pont, 1978)
  5. Teratology - rabbit: Teratogenic NOEL=75 mg/kg/day; Fetotoxic NOEL=25 mg/kg/day; Fetotoxic LEL=75 mg/kg/day (increased incidence of resorption); core grade minimum (du Pont, 1980d)

Data Gap(s): None

Other Data Reviewed

  1. 2-Year Feeding (oncogenic) - mice: Systemic NOEL=500 ppm (75 mg/kg/day); Systemic LEL=5000 ppm (decreased body weight and food consumption); core grade guideline (du Pont, 1981)
  2. 90-Day Feeding - rat: NOEL=100 ppm (5 mg/kg/day) (LDT); LEL=5000 ppm (25 mg/kg/day) (slight decrease in plasma creatinine, slight increased hematocrit); core grade minimum (du Pont, 1980e)

__I.A.5. Confidence in the Oral RfD

Study — High
Database — High
RfD — High

The principal study appears to be of good quality and is given a high rating. Additional studies are also of good quality, and therefore, the database given a high confidence rating. 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 files

Agency Work Group Review — 04/08/1986

Verification Date — 04/08/1986

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 Chlorsulfuron 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).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Chlorsulfuron
CASRN — 64902-72-3

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Chlorsulfuron
CASRN — 64902-72-3

This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.

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


_VI.  Bibliography

Substance Name — Chlorsulfuron
CASRN — 64902-72-3
Last Revised — 01/01/1990

_VI.A. Oral RfD References

E.I. du Pont de Nemours & Company, Inc. 1978. MRID No. 00031424. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1980a. MRID No. 00031419, 00086003. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1980b. MRID No. 00031420. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1980c. MRID No. 00031423. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1980d. MRID No. 00086827. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1980e. MRID No. 00031421. Available from EPA. Write to FOI, EPA, Washington DC 20460.

E.I. du Pont de Nemours & Company, Inc. 1981. MRID No. 00090030. Available from EPA. Write to FOI, EPA, Washington DC 20460.

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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 — Chlorsulfuron
CASRN — 64902-72-3

Date
Section
Description
03/31/1987 IV. Regulatory Action section on-line
01/01/1990 I.A. Prinicipal study year corrected
01/01/1990 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 — Chlorsulfuron
CASRN — 64902-72-3
Last Revised — 01/31/1987

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