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Prometryn
CASRN 7287-19-6
Contents
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 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 NOEL: 150 ppm diet 1000 1 4E-3
degeneration and (3.75 mg/kg/day) mg/kg/day
bone marrow atrophy
LEL: 1500 ppm diet
106-Week Dog Feeding (37.5 mg/kg/day)
Study
Ciba-Geigy, 1965a
*Dose Conversion Factors & 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 data base 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 COMMENTS (ORAL RfD)
This chemical has a very old data base. 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
Data Base -- 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 data base 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
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.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.
_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
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)-
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0258.HTM
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