Propazine (CASRN 139-40-2)
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0187
Propazine;
CASRN 139-40-2
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 Propazine
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 10/01/1990 |
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 — Propazine
CASRN — 139-40-2
Last Revised — 10/01/1990
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 |
---|---|---|---|---|
Decrease in body 2-Year Rat Feeding Ciba-Geigy, 1980a |
NOEL: 100 ppm (diet) LEL: 1000 ppm (diet) |
300
|
1
|
2E-2
mg/kg/day |
*Conversion Factors -- 1 ppm = 0.05 mg/kg/day (assumed rat food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
Ciba-Geigy Corporation. 1980a. MRID No. 00041408, 00076955, 00087893. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Two hundred and sixty males and 260 female CD rats were selected randomly and given 0, 3, 100 or 1000 ppm of propazine in their diets for 2 years. Seventy animals of each sex were placed in the control and high dose group. Sixty animals of each sex were placed in the low and mid-dose groups. At 1000 ppm there was a significant decrease in body weight in both sexes. There was a significant increase in mammary tumors in females at 1000 ppm. The NOEL for systemic effects was 100 ppm (5 mg/kg/day).
An RfD based on the subchronic dog NOEL of 5 mg/kg/day and a 1000 UF, to account for inter- and intraspecies differences and a subchronic-to-chronic extrapolation, would yield a value similar to the RfD.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An uncertainty factor of 100 is used to account for the inter- and intraspecies differences. An additional UF is used to account for the fact that the database on chronic toxicity lacks an adequate second mammalian bioassay (that is, a chronic feeding study in the dog may yield a more sensitive toxicological endpoint). However, since the 90-day studies in rats and dogs do not show an order of magnitude species difference, an additional 3-fold UF is considered appropriate.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Data Considered for Establishing the RfD:
1) 2-Year Feeding (oncogenic) - Rat: Principal study - see previous description; core grade minimum
2) 3-Generation Reproduction - Rat: NOEL=5 mg/kg/day; LEL=50 mg/kg/day (reduced mean pup body weight); core grade minimum (Ciba-Geigy, 1979)
3) Teratology - Rat: Fetotoxic NOEL=100 mg/kg/day; Fetotoxic LEL=300 mg/kg/day; Maternal Toxic NOEL=100 mg/kg/day; Maternal Toxic LEL=300 mg/kg/ day; core grade supplementary (Ciba-Geigy, 1976)
4) 90-Day Feeding - Dog: NOEL=200 ppm (5 mg/kg/day); LEL=1000 ppm (HDT) (25 mg/kg/day) (decreased body weight); no core grade (Ciba-Geigy, 1967)
Other Data Reviewed:
1) 2-Year Feeding (oncogenic) - Mouse: Systemic NOEL=15 mg/kg/day; Systemic LEL=450 mg/kg/day; (increased focal myocardial fibrosis and focal myocardial degeneration); core grade minimum (Ciba-Geigy, 1980b)
Data Gap(s): Chronic Dog Feeding Study; Rat Teratology Study; Rabbit Teratology Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical study appears to be of fair quality and is given a medium confidence rating. Additional studies are supportive, but because there are data gaps, the database is given a medium confidence rating. Medium confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Files
Agency Work Group Review — 08/19/1986, 09/29/1986, 05/20/1987
Verification Date — 05/20/1987
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 Propazine conducted in November 2001 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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Propazine
CASRN — 139-40-2
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Propazine
CASRN — 139-40-2
Not available at this time.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Propazine
CASRN — 139-40-2
Last Revised — 10/01/1990
_VI.A. Oral RfD References
Ciba-Geigy Corporation. 1980a. MRID No. 00041408, 00076955, 00087893. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1979. MRID No. 00041409. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1976. MRID No. 00087879. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1967. MRID No. 0011680. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Ciba-Geigy Corporation. 1980b. MRID No. 00044335. 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 — Propazine
CASRN — 139-40-2
Date |
Section |
Description |
---|---|---|
08/28/1987 | I.A. | UF reevaluated - RfD changed |
10/01/1990 | I.A.4. | Citations added |
10/01/1990 | III.A. | Health Advisory on-line |
10/01/1990 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory Action section 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. |
_VIII. Synonyms
Substance Name — Propazine
CASRN — 139-40-2
Last Revised — 03/31/1987
- 139-40-2
- 2,4-BIS(ISOPROPYLAMINO)-6-CHLORO-s-TRIAZINE
- 2,4-BIS(PROPYLAMINO)-6-CHLOR-1,3,5-TRIAZIN
- 2-CHLORO-4,6-BIS(ISOPROPYLAMINO)-s-TRIAZINE
- 6-CHLORO-N,N'-BIS(1-METHYLETHYL)-1,3,5-TRIAZINE-2,4-DIAMINE
- G-30028
- GEIGY 30,028
- GESAMIL
- MILOGARD
- PLANTULIN
- PRIMATOL P
- PROPASIN
- PROPAZIN
- Propazine
- PROZINEX
- s-TRIAZINE, 2-CHLORO-4,6-BIS(ISOPROPYLAMINO)-
- 1,3,5-TRIAZINE-2,4-DIAMINE, 6-CHLORO-N,N'-BIS(1-METHYLETHYL)-