|
Alar
CASRN 1596-84-5
Contents
0287
Alar; CASRN 1596-84-5
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 Alar
File On-Line 06/30/1988
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 07/01/1991
Inhalation RfC Assessment (I.B.) no data 02/01/1991
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
Last Revised -- 07/01/1991
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
-------------------- ----------------------- ----- --- ---------
No adverse effects NOEL: 300 ppm (15 100 1 1.5E-1
mg/kg/day) mg/kg/day
3-Generation
Reproduction Rat LEL: none
Study
Uniroyal Chemical, 1966
*Conversion Factor: 1 ppm = 0.05 mg/kg/day (assumed rat food consumption)
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Uniroyal Chemical. 1966. MRID No. 0009413. Available from EPA. Write to
FOI, EPA, Washington, DC 20460.
Three-generation reproduction and lactation studies were conducted with rats
from the 2 year feeding study and a control group. When the rats were
approximately 100 days of age, 20 pairs of males and females were separated
from the 300 ppm (15 mg/kg/day) dosage group. Fertility, gestation,
viability, lactation, and litter body weights were similar thru two cycles of
each generation. There was no evidence of adverse effects by any criteria of
performance at 300 ppm (15 mg/kg/day).
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 100 was used to account for the intra- and
interspecies differences.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
A 2-generation reproduction study (Uniroyal Chemical Co., 1987) is currently
under review.
Data Considered for Establishing the RfD:
1) 3-Generation Reproduction - rat: Principal study - see previous
description; no core grade
2) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=3000 ppm (150 mg/kg/day)
(HDT); no core grade (Uniroyal Chemical, 1966)
3) 2-Year Feeding - dog: NOEL=3000 ppm (75 mg/kg/day) (HDT); no core grade
(U.S. Rubber Co., 1966)
4) 2-Year Feeding (oncogenic) - rat: Systemic NOEL=10,000 ppm (500 mg/kg/day)
(HDT); (LDT; adenocarcinomas of the endomethrium and leiomyosarcomas of the
uterus in females); no core grade (NCI, 1978)
5) Teratology - rat: Developmental NOEL=390 mg/kg/day; Developmental LEL=1800
mg/kg/day (HDT; fetotoxic skeletal malformations); core grade supplementary
(Uniroyal Chemical, 1978)
Other Data Reviewed:
1) 2-Year Feeding (oncogenic) - mouse: Systemic NOEL=5000 ppm (750
mg/kg/day); Systemic LEL=10,000 ppm (1500 mg/kg/day) (decreased body weight
and survival in females); no core grade (NCI, 1978)
2) 90-Day Feeding - rat: NOEL=2160 mg/kg/day (HDT); no core grade (Uniroyal
Chemical, 1964)
3) 2-Year Feeding (oncogenic) - rat: NOEL=10,000 ppm (500 mg/kg/day) (HDT);
core grade supplementary (Uniroyal Chemical Co., 1986a)
4) 2-Year Feeding (oncogenic) - mouse: Erthrocyte count, hemoglobin level and
hematocrit are somewhat lower in males of 10,000 ppm level (HDT); no core
grade (Uniroyal Chemical Co., 1986b)
Data Gap(s): Rat Teratology Study; Rabbit Teratology Study
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Low
Data Base -- Medium
RfD -- Low
The critical study is given a low confidence rating. Because of the extensive
but questionable quality of the data base, the submission of a new
reproduction study and the pending submission of new chronic rat and mouse
studies, the data base is given a medium confidence rating. Therefore,
confidence in the RfD can be considered low to medium.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- Pesticide Registration Files
Agency Work Group Review -- 09/16/1987
Verification Date -- 09/16/1987
___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 -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
Last Revised -- 07/01/1991
__VI.A. ORAL RfD REFERENCES
NCI (National Cancer Institute). 1978. Bioassay of Daminozide for Possible
Carcinogenicity. NCI Carcinogenesis Technical Report Series No. 83. DHEW
Publication No. (NIH) 78-1333.
Uniroyal Chemical. 1964. MRID No. 00009727.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1966. MRID No. 0009413.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical Company. 1978. MRID No. 00053764.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical Company. 1986a. MRID No. 00016266.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical Company. 1986b. MRID No. 40093501k, 40451001.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical Company. 1987. MRID No. 40233901.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
United States Rubber Company. 1966. MRID No. 00094113.
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 -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
08/22/1988 I.A.4. Study 4) text revised
02/01/1991 I.B. Incorrect message removed
07/01/1991 I.A. Principal study clarified
07/01/1991 I.A.4. Citations clarified
07/01/1991 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- Alar
CASRN -- 1596-84-5
Primary Synonym -- Daminozide
Last Revised -- 06/30/1988
1596-84-5
Alar
ALAR-85
AMINOZIDE
B-9
B 995
BERNSTEINSAEURE-2,2-DIMETHYLHYDRAZID
B-NINE
BUTANEDIOIC ACID MONO(2,2-DIMETHYLHYDRAZIDE)
Daminozide
DIMAS
DIMETHYLAMINOSUCCINAMIC ACID
2,2-DIMETHYLHYDRAZID KYSELINY JANTAROVE
DMASA
DMSA
KYLAR
NCI-C03827
N-DIMETHYL AMINO-beta-CARBAMYL PROPIONIC ACID
N-(DIMETHYLAMINO)SUCCINAMIC ACID
N-DIMETHYLAMINO-SUCCINAMIDSAEURE
SADH
SUCCINIC ACID 2,2-DIMETHYLHYDRAZIDE
SUCCINIC ACID, MONO(2,2-DIMETHYLHYDRAZIDE)
SUCCINIC 1,1-DIMETHYL HYDRAZIDE
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0287.HTM
|
