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Phosmet (CASRN 732-11-6)

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0091

Phosmet; CASRN 732-11-6

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 Phosmet

File First On-Line 01/31/1987

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) on-line 01/01/1992
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 — Phosmet
CASRN — 732-11-6
Last Revised — 01/01/1992

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

Reduced body weight
(males), liver cell
vacuolation,
cholinerase
inhibition

2-Year Rat Feeding
Study

Stauffer Chemical, 1967

NOEL: 40 ppm
(2.0 mg/kg/day)

LEL: 400 ppm
(20.0 mg/kg/day)

100
1
2E-2
mg/kg/day

*Dose Conversion Factors & Assumptions: 1 ppm = 0.05 mg/kg/day (assumed rat food consumption)

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

Stauffer Chemical Company. 1967. MRID No. 00062651, 00075419, 00076436, 00080431, 00080556; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Phosmet was administered in the diet at levels of 20, 40, and 400 ppm to groups of 25 Charles River strain albino rats/sex for a period of 2 years. A control was included. There was slight decrease in body weight gain in males in the 400 ppm group. Plasma, erythrocyte, and brain cholinesterase activity was decreased in the 400 ppm group. Moderate liver cell vacuolation was observed in rats in the 400 ppm group.

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

UF — Based on a chronic exposure study, an uncertainty factor of 100 was used to account for inter- and intra- species differences.

MF — None

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

The NOEL in a 2-year dog study is 1 mg/kg/day, less than the NOEL used in support of the RfD. However, since systemic effects were noted in the rat, a l00 fold UF was applied to the rat NOEL (2.0 mg/kg/day) rather than a l0-fold UF applicable to the ChE inhibition observed in the dog. Thus, overall a more restrictive RfD value was calculated.

Data Considered for Establishing the RfD

1) 2-Year Feeding (Oncogenic) - rat: Systemic NOEL=40 ppm (2 mg/kg/day); ChE NOEL=40 ppm; LEL=400 ppm (20 mg/kg/day) (decreased body weight gain in males; increased incidence of moderate liver cell vacuolation; inhibition of plasma, erythrocyte and brain cholinesterase activity); core grade minimum (Stauffer Chemical Co., 1967)

2) 2-Year Feeding - dog: NOEL=40 ppm (1.0 mg/kg/day); LEL=400 ppm (10 mg/kg/day) (inhibition of erythrocyte and brain cholinesterase activity); core grade minimum (Stauffer Chemical Co., 1967)

3) 3-Generation Reproduction - rat: NOEL=80 ppm (4 mg/kg/day) (HDT); core grade minimum (Stauffer Chemical Co., 1968a)

4) Teratology - rabbit: Teratogenic and Reproductive NOEL=60 mg/kg (HDT) (cholinesterase activity inhibited from 10 mg/kg upwards); core grade minimum (Stauffer Chemical Co., 1966a)

5) Teratology - monkey: NOEL=8 mg/kg (HDT); core grade minimum (Stauffer Chemical Co., 1968b)

Data Gap(s): None

Other Data Reviewed

1) Teratology - rabbit: NOEL=35 mg/kg/day (HDT); core grade supplementary (Stauffer Chemical Co., 1966b)

2) Teratology - rat: NOEL=30 mg/kg/day (HDT) (reduced maternal body weight gain at 30 mg/kg/day); core grade supplementary (Stauffer Chemical Co., 1979)

3) Teratology - rat: NOEL=25 mg/kg/day (gavage) and 29 mg/kg/day (diet); core grade supplementary (Stauffer Chemical Co., 1976)

__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 confidence rating. Additional studies are of good quality; therefore, the database is given a high confidence rating. High confidence in the RfD follows.

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

Pesticide Registration Standard, April 1986

Pesticide Registration Files

Agency Work Group Review — 06/10/1986

Verification Date — 06/10/1986

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 Phosmet 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 — Phosmet
CASRN — 732-11-6

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Phosmet
CASRN — 732-11-6

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 — Phosmet
CASRN — 732-11-6
Last Revised — 01/01/1992

_VI.A. Oral RfD References

Stauffer Chemical Company. 1966a. MRID No. 00062649, 00080433, 0009076; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1966b. MRID No. 00062649; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1967. MRID No. 00062651, 00075419, 00076436, 00080431, 00080556; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1968a. MRID No. 00062650, 00081432; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1968b. MRID No. 00112269; HED Doc. No. 001999. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1976. MRID No. 00063192; HED Doc. No. 005102. Available from EPA. Write to FOI, EPA, Washington, DC 20460.

Stauffer Chemical Company. 1979. MRID No. 00031555; HED Doc. No. 001999. 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 — Phosmet
CASRN — 732-11-6

Date
Section
Description
03/31/1987 IV. Regulatory Action section on-line
01/01/1992 I.A.4. Citations added
01/01/1992 IV. Regulatory actions updated
01/01/1992 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.

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_VIII.  Synonyms

Substance Name — Phosmet
CASRN — 732-11-6
Last Revised — 01/31/1987

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