Prometryn (CASRN 7287-19-6)
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0258
Prometryn;
CASRN 7287-19-6
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 Prometryn
File First On-Line 09/30/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 07/01/1992 |
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 — Prometryn
CASRN — 7287-19-6
Last Revised — 07/01/1992
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
|
---|---|---|---|---|
Liver and kidney 106-Week Dog Feeding Ciba-Geigy, 1965a |
NOEL: 150 ppm diet LEL: 1500 ppm diet |
1000
|
1
|
4E-3
mg/kg/day |
*Conversion Factors and Assumptions — 1 ppm = 0.025 mg/kg/day (assumed dog food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
Ciba-Geigy Corporation. 1965a. MRID No. 00042794; HED Doc. No. 001830, 003500, 005665, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Groups of 3 male and 3 female beagles were dosed with prometryn 80W (80% wettable powder) in their feed for 106 weeks at active ingredient (a.i.) concentration levels of 0 (vehicle control), 15, 150, and 1500 ppm (0, 0.375, 3.75, and 37.5 mg/kg/day). The dogs were observed daily, weighed weekly, given physical examinations daily for the first week and weekly thereafter, and given neurologic and ophthalmic examinations monthly. Food consumption was measured daily. The following clinical pathology measurements were made: Hematology - hematocrit, hemoglobin, sedimentation rate, and leukocytes (total and differential); Clinical Chemistry - BUN, glucose, alkaline phosphatase, and SGOT; Urinalysis - specific gravity, pH, albumin, sugar, appearance, and microscopic sediment. All surviving dogs were sacrificed at 106 weeks and examined grossly. A battery of tissues were examined histopathologically. The defined doses were as follows: NOEL = 3.75 mg a.i./kg/day (150 ppm a.i.); LEL = 37.5 mg a.i./kg/day (1500 ppm a.i.) - degenerative hepatic changes, renal tubule degeneration, and slight bone marrow atrophy.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — A 100-fold UF has been used to compensate for the inter- and intraspecies differences in extrapolating from the dog to the human. An additional UF of 10 was used because the existing database does not unequivocally establish that the dog is the most sensitive species. The other studies (each having a higher NOEL) are of insufficient quality.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
This chemical has a very old database. The RfD was established on the data available and given a low confidence.
Data Considered for Establishing the RfD:
1) 106-Week Feeding (80W) - dog: Principal study - see previous description; core grade minimum
2) 104-Week Feeding/Oncogenicity (50WP) - rat: Systemic NOEL=1250 ppm a.i. (62.5 mg a.i./kg/day, HDT); Systemic LEL=none; core grade supplementary (Ciba- Geigy, 1965b)
3) 3-Generation Reproduction (50WP) - rat: Reproductive NOEL=100 ppm a.i. (5.0 mg a.i./kg/day, HDT); LEL=none; core grade supplementary (Ciba-Geigy, 1966)
4) Teratogenicity (technical) - rabbit: Maternal NOEL=12 mg/kg/day; Maternal LEL=72 mg/kg/day (decreased food consumption-HDT); Embryotoxic NOEL=72 mg/kg/day; LEL=none; Fetotoxic NOEL=12 mg/kg/day; Fetotoxic LEL=72 mg/kg/day (increased fetal resorptions-HDT); Teratogenic NOEL=72 mg/kg/day (HDT); LEL=none; Developmental toxicity index=1; core grade minimum (Ciba-Geigy, 1985)
5) Teratogenicity - Rat NOEL and LEL values could not be defined with any degree of certainty because of the lack of individual animal data. There were reportedly no compound-related developmental anomalies at the HDT (250 mg/kg/day); core grade supplementary (Ciba-Geigy, 1977)
Data Gap(s): Chronic Rat Feeding Study; Rat Reproduction Study; Rat Teratology Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
The principal study is old, but appears to be of satisfactory quality and is given a medium rating. The confidence in the database is low. Therefore, the confidence in the assigned RfD is low.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Standard (1986)
Pesticide Registration Files
Agency Work Group Review — 12/09/1986, 04/15/1987
Verification Date — 04/15/1987
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 prometryn 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 — Prometryn
CASRN — 7287-19-6
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Prometryn
CASRN — 7287-19-6
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 — Prometryn
CASRN — 7287-19-6
Last Revised — 07/01/1992
_VI.A. Oral RfD References
Ciba-Geigy Corporation. 1965a. MRID No. 00042794; HED Doc. No. 001830, 003500, 005665, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1965b. MRID No. 00042794; HED Doc. No. 001830, 003500, 005665, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1966. MRID No. 00024472; HED Doc. No. 001830, 003500, 005665, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1977. MRID No. 00060644, 40457516; HED Doc. No. 001832, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1985. MRID No. 00157995; HED Doc. No. 005665, 005666. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
_VI.B. Inhalation RfD References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Prometryn
CASRN — 7287-19-6
Date |
Section |
Description |
---|---|---|
01/01/1992 | IV. | Regulatory Action section on-line |
07/01/1992 | I.A.1. | Short citation clarified |
07/01/1992 | I.A.2. | Principal study clarified |
07/01/1992 | I.A.4. | Citations added |
07/01/1992 | VI.A. | Oral RfD references 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. |
10/28/2003 | I.A.6 | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Prometryn
CASRN — 7287-19-6
Last Revised — 09/30/1987
- 7287-19-6
- 2,4-BIS(ISOPROPYLAMINO)-6-METHYL MERCAPTO-s-TRIAZINE
- 2,4-BIS(ISOPROPYLAMINO)-6-METHYLTHIO-1,3,5-TRIAZINE
- 2,4-BIS(ISOPROPYLAMINO)-6-METHYLTHIO-s-TRIAZINE
- 2,4-BIS(PROPYLAMINO)-6-METHYLTHIO-1,3,5-TRIAZIN
- CAPAROL
- G 34161
- GESAGARD
- MERKAZIN
- 2-METHYLMERCAPTO-4,6-BIS(ISOPROPYLAMINO)-s-TRIAZINE
- 2-METHYLTHIO-4,6-BIS(ISOPROPYLAMINO)-s-TRIAZINE
- N,N'-BIS(1-METHYLETHYL)-6-METHYL-THIO-1,3,5-TRIAZINE-2,4-DIAMINE
- POLISIN
- PRIMATOL Q
- PROMETREX
- PROMETRIN
- Prometryn
- PROMETRYNE
- SELEKTIN
- SESAGARD
- s-TRIAZINE, 4,6-BIS(ISOPROPYLAMINO)-2-METHYLMERCAPTO-
- s-TRIAZINE, 2,4-BIS(ISOPROPYLAMINO)-6-(METHYLTHIO)-