Metalaxyl (CASRN 57837-19-1)
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0068
Metalaxyl;
CASRN 57837-19-1
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 Metalaxyl
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 01/01/1995 |
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 — Metalaxyl
CASRN — 57837-19-1
Last Revised — 01/01/1995
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 |
---|---|---|---|---|
Increased serum 6-Month Feeding Dog Ciba-Geigy, 1981a |
NOEL: 250 ppm (6.25 mg/kg/day) LEL: 1000 ppm (25 mg/kg/day) |
100 |
1 |
6E-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)
Ciba-Geigy Corporation. 1981a. MRID No. 00071598. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Four groups of 6 male and 6 female dogs were given diets containing 0, 50, 250, or 1000 ppm metalaxyl for 6 months. Two dogs of each sex were also added to the control and high-dose groups to be continued on control diets after termination of the feeding period. Alkaline phosphatase levels in the dogs given the 1000 ppm diet were significantly higher than those for control group dogs at the 4-, 5-, and 6-month observations. Liver-to-brain weight ratios for the high dose group females were significantly increased in comparison with control group values, and absolute liver weights and liver-to-body weight ratios showed a dose-related trend toward increasing liver weight. However, these trends were not statistically significant. These results suggested a NOEL of 250 ppm (6.3 mg/kg/day) and an LEL of 1000 ppm (25 mg/kg/day).
__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 the inter- and intraspecies differences. An additional UF of 10 to account for the subchronic (6-month) nature of the dog study was not considered necessary since the 3-month rat study and the 2-year rat study have the same NOEL, thus indicating that the effects seen in subchronic exposure studies are not likely to be exacerbated in chronic exposure studies.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD
- 6-Month Feeding - dog: Principal study - see discussion above; core grade minimum
- 3-Month Feeding - rat: NOEL=250 ppm (12.5 mg/kg/day); LEL=1250 ppm (62.5 mg/kg/day) (decreased food consumption and minimal cellular hypertrophy in parenchymal cells); core grade guideline (Ciba-Geigy, 1977)
- Teratology - rat: Teratogenic NOEL=400 mg/kg/day (HDT); Fetotoxicity NOEL=50 mg/kg/day; LEL=250 mg/kg/day (unossified sternebrae); Maternal toxicity NOEL=50 mg/kg/day; LEL=250 mg/kg/day (convulsions, ataxia); core grade minimum (Ciba-Geigy, 1985)
- Teratology - rabbit: Maternal toxicity NOEL=150 mg/kg/day; LEL=300 mg/kg/day (HDT) (2.3% body weight loss supported by preliminary range-finding study results, weight loss more pronounced at 500 mg/kg/day in preliminary study and mortality at 1000 mg/kg/day dose level in range-finding study); Embryotoxicity, Fetotoxicity and Teratogenicity NOEL=300 mg/kg/day (HDT); core grade minimum (Ciba-Geigy, 1984)
- 3-Generation Reproduction - rat: Reproductive Effects NOEL=1250 ppm (62.5 mg/kg/day) (HDT); core grade minimum (Ciba-Geigy, 1980a)
- 2-Year Chronic Feeding (oncogenic) - rat: Systemic NOEL=250 ppm (12.5 mg/kg/day); LEL=1250 ppm (62.5 mg/kg/day) (HDT) (Increased liver weight and periacinar vacuolization of hepatocytes); core grade minimum (Ciba-Geigy, 1980b)
Data Gap(s): None
Other Data Reviewed
- 2-Year Oncogenic - mice: Systemic NOEL=250 ppm (37.5 mg/kg/day); LEL=1250 ppm (87.5 mg/kg/day) (fatty infiltration of liver); core grade minimum (Ciba- Geigy, 1981b)
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — High
RfD — High
The principal study appears to be of good quality and is given a medium confidence rating. Additional studies are of good quality and there are no data gaps; 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 — 07/08/1986, 12/08/1994
Verification Date — 07/08/1986
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 Metalaxyl conducted in August 2003 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 — Metalaxyl
CASRN — 57837-19-1
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Metalaxyl
CASRN — 57837-19-1
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 — Metalaxyl
CASRN — 57837-19-1
Last Revised — 03/01/1991
_VI.A. Oral RfD References
Ciba-Geigy Corporation. 1977. MRID No. 00084110. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1980a. MRID No. 00071600, 00130952. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1980b. MRID No. 00071565, 00080302, 00098481, 00130950. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1981a. MRID No. 00071598. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1981b. MRID No. 00103354, 00127880, 00130951. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1984. MRID No. 00144371. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1985. MRID No. 00144422, 00144423. 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 — Metalaxyl
CASRN — 57837-19-1
Date |
Section |
Description |
---|---|---|
03/31/1987 | IV. | Regulatory Action section on-line |
03/01/1991 | I.A.4. | Citations added |
03/01/1991 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory action updated |
01/01/1995 | I.A. | Oral RfD noted as pending change |
01/01/1995 | I.A.6. | Work group review date added |
08/01/1995 | I.A., I.A.6. | 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. |
10/28/2003 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Metalaxyl
CASRN — 57837-19-1
Last Revised — 01/31/1987
- 57837-19-1
- ALANINE, N-(METHOXYACETYL)-N-(2,6-XYLYL)-, METHYL ESTER, DL-
- APRON 2E
- CG 117
- CGA 48988
- DL-ALANINE, N-(2,6-DIMETHYLPHENYL)-N-(METHOXYACETYL)-,METHYL ESTER
- METALAXIL
- Metalaxyl
- N-(2,6-DIMETHYLPHENYL)-N-(METHOXYACETYL)-ALANINE METHYL ESTER
- N-(2,6-DIMETHYLPHENYL)-N-(METHOXYACETYL)-DL-ALANINE METHYL ESTER
- RIDOMIL
- RIDOMIL 2E
- SUBDUE
- SUBDUE 2E
- SUBDUE 5SP