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Chlorpyrifos (CASRN 2921-88-2)

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Chlorpyrifos; CASRN 2921-88-2

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 Chlorpyrifos

File First On-Line 01/31/1987

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) on-line 03/01/1988
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 — Chlorpyrifos
CASRN — 2921-88-2
Last Revised — 03/01/1988

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 plasma ChE
activity after 9 days.

20-Day Human
Cholinesterase
Inhibition Study

Dow Chemical, 1972
NOEL: 0.03 mg/kg/day

LOEL: 0.10 mg/kg/day
10
1
3E-3
mg/kg/day

*Conversion Factors: none

__I.A.2. Principal and Supporting Studies (Oral RfD)

Dow Chemical Company. 1972. Accession No. 112118. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Sixteen human male volunteers were treated (4/dose) with 0, 0.014, 0.03, or 0.10 mg/kg/day of chlorpyrifos by capsule for a total of 20 days at the low and mid dose, and for 9 days at the high dose. Treatment of the high-dose group (0.1 mg/kg/day) was discontinued after 9 days due to a runny nose and blurred vision in one individual. Mean plasma ChE in this group was inhibited by about 65% compared to the control average. No effect on RBC ChE activity was apparent at any dose.

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

UF — The UF of 10 is the standard factor allowing for the range of human sensitivity for cholinesterase inhibition.

MF — None 

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

Data Considered for Establishing the RfD

1) 20-day ChE inhibition study - humans: Principal study - see previous description

2) Chronic feeding - dog: Plasma ChE NOEL=0.01 mg/kg/day (LDT); NOEL (other effects)=3.0 mg/kg/day (HDT); core grade minimum (Dow Chemical, 1971a)

3) Chronic feeding - rat: Plasma ChE NOEL=0.1 mg/kg/day; NOEL (other effects)=3.0 mg/kg/day (HDT); few animals used (Dow Chemical, 1971b)

4) Reproduction - rat: ChE NOEL=0.1 mg/kg/day; Reproductive NOEL=1.0 mg/kg/day (HDT); core grade minimum (Dow Chemical, 1971c)

5) Teratology - rat: Maternal (ChE) NOEL=0.1 mg/kg/day; Developmental NOEL=15 mg/kg/day (HDT); core grade minimum (Dow Chemical, 1983)

6) Teratology - mouse: Maternal (ChE) NOEL=0.1 mg/kg/day; Developmental NOEL=10 mg/kg/day (decreased fetal length, increased skeletal variations at 25 mg/kg/day); core grade minimum (Dow Chemical, 1979)

Data Gap(s): Chronic feeding/oncogenicity - rat.

__I.A.5. Confidence in the Oral RfD

Study — Medium
Database — Medium
RfD — Medium

The principal human study was limited because only 4 males/dose were studied, but several doses were used; thus, the study is given a medium to low confidence rating. The available experimental data in rats, dogs, rabbits, and mice appears to be similar to the NOEL for ChE inhibition in humans; thus, confidence in the database is rated medium. Medium confidence in the RfD follows.

__I.A.6. EPA Documentation and Review of the Oral RfD

Office of Pesticide Programs files

Agency Work Group Review — 03/11/1986

Verification Date — 03/11/1986

__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 — Chlorpyrifos
CASRN — 2921-88-2

Not available at this time.

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_II. Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Chlorpyrifos
CASRN — 2921-88-2

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 — Chlorpyrifos
CASRN — 2921-88-2
Last Revised — 11/10/1989

_VI.A. Oral RfD References

Dow Chemical Company. 1972. Accession No. 112118. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Dow Chemical USA. 1971a. MRID No. 00029063, 00064933, 00146519. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Dow Chemical USA. 1971b. MRID No. 00081270, 00095178. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Dow Chemical USA. 1971c. MRID No. 00029064, 00064934. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Dow Chemical USA. 1979. MRID No. 00095268. Available from EPA. Write to FOI, EPA, Washington DC 20460.

Dow Chemical USA. 1983. MRID No. 00130400. 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 — Chlorpyrifos
CASRN — 2921-88-2

Date
Section
Description
03/01/1988 I.A.5. Core grades added
11/01/1989 VI. Bibliography on-line
01/01/1992 IV. Regulatory actions 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.
02/22/2001 I.A., II. This chemical is being reassessed under the IRIS Program.
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).

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_VIII. Synonyms

Substance Name — Chlorpyrifos
CASRN — 2921-88-2
Last Revised — 01/31/1987

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