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Amdro
CASRN 67485-29-4
Contents
0207
Amdro; CASRN 67485-29-4
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 Amdro
File On-Line 09/30/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 09/30/1987
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 -- Amdro
CASRN -- 67485-29-4
Last Revised -- 09/30/1987
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 organ NOEL: 0.33 mg/kg/day 1000 1 3E-4
weights mg/kg/day
LEL: 1.0 mg/kg/day
26-Week Dog Feeding
Study
American Cyanamid,
1980
*Conversion Factors: none
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
American Cyanamid Company. 1980. MRID No. 00035529. Available from EPA.
Write to FOI, EPA, Washington, DC 20460.
Amdro (AC 217,300) was administered to 4 dogs/sex/dose for 26 weeks. The dose
levels were 0 (control), 0.33, 1.0, and 3.0 mg/kg/day after the dogs had been
fed. The only compound-related effects were increased liver weights and
increased liver/body weight and brain/body weight ratios. Pathology, clinical
chemistry, and hematology were unremarkable. The effects were noted at the
1.0 and 3.0 mg/kg/day levels, but not at the 0.33 mg/kg/day level.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 100 was used to account for the inter- and
intraspecies differences. An additional UF of l0 was used since the critical
study was only 26 weeks, instead of at least 1 year; additionally, the effects
in dogs are shown to become more intense with time, as evidenced by comparison
with the l3-week study.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
Data Considered for Establishing the RfD:
1) 26-Week Feeding - dog: Principal study - see previous description; core
grade minimum
2) 2-Year Feeding - rat: NOEL=50 ppm (2.5 mg/kg/day); LEL=100 ppm (5
mg/kg/day) (decreased testicular weight, testicular atrophy, decreased LDH
values, organ weight changes, decreased food consumption and weight gain);
core grade minimum (American Cyanamid, 1982a)
3) 3-Generation Reproduction - rat: Maternal NOEL=50 ppm (2.5 mg/kg/day);
Maternal LEL=100 ppm (5 mg/kg/day) (decreased food consumption, body weight
gain); Reproductive NOEL=50 ppm; Reproductive LEL=100 ppm (male infertility);
core grade minimum (American Cyanamid, 1982b)
4) Teratology - rat: Maternal NOEL=3 mg/kg/day; Maternal LEL=10 mg/kg/day
(decreased mean body weight gain and discoloration of body fat); Fetal toxic
NOEL=10 mg/kg/day; Fetal toxic LEL=30 mg/kg/day (decreased fetal weight);
Teratogenic NOEL=30 mg/kg/day; LEL=none; core grade minimum (American
Cyanamid, 1979a)
5) Teratology - rabbit: Maternal NOEL=none; Maternal LEL=5 mg/kg/day
(decreased body weight gain); Fetotoxic NOEL=5 mg/kg/day; Fetotoxic LEL= 10
mg/kg/day (reduced fetal weight gain); Teratogenic NOEL=20 mg/kg/day;
LEL=none; core grade minimum (American Cyanamid, 1982c)
Other Data Reviewed:
1) 18-Month Feeding (oncogenic) - mouse: Systemic NOEL=25 ppm (2.75
mg/kg/day); Systemic LEL=50 ppm (3.75 mg/kg/day) (increased testicular
lesions, decreased body weight gain, increased renal amyloidosis); core grade
minimum (American Cyanamid, 1982d)
2) 90-Day Feeding - dog: NOEL=3 mg/kg/day; LEL=6 mg/kg/day (testicular
atrophy and decreased body weight and food consumption); core grade minimum
(American Cyanamid, 1979b)
3) 90-Day Feeding - rat: NOEL=50 ppm (2.5 mg/kg/day); LEL=100 ppm (5
mg/kg/day) (testicular atrophy and decreased body weight); core grade minimum
(American Cyanamid, 1979c)
Data Gap(s): None
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- High
RfD -- High
The chosen study provides sufficient data to rate a medium confidence. The
data base provides sufficient data to rate a high confidence, although some of
the studies are of good but not outstanding quality. The total evaluation
provides for high confidence in the derived RfD.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Pesticide Registration Files
Agency Work Group Review -- 03/11/1986, 05/20/1987
Verification Date -- 05/20/1987
___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 -- Amdro
CASRN -- 67485-29-4
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Amdro
CASRN -- 67485-29-4
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Amdro
CASRN -- 67485-29-4
Last Revised -- 11/01/1989
__VI.A. ORAL RfD REFERENCES
American Cyanamid Company. 1979a. MRID No. 00032638, 00061790. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1979b. MRID No. 00032634, 00061794. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1979c. MRID No. 00032641, 00061793. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1980. MRID No. 00035529. Available from EPA.
Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1982a. MRID No. 00035527, 00061768, 00101565,
00126106. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1982b. MRID No. 00035525, 00101575. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1982c. MRID No. 00101558. Available from EPA.
Write to FOI, EPA, Washington, DC 20460.
American Cyanamid Company. 1982d. MRID No. 00035526, 00061767, 00101563,
00109466. 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 -- Amdro
CASRN -- 67485-29-4
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
11/01/1989 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- Amdro
CASRN -- 67485-29-4
Last Revised -- 09/30/1987
67485-29-4
AC 217300
Amdro
CL 217300
2(1H)-PYRIMIDINONE, TETRAHYDRO-5,5-DIMETHYL-, (3-(4-TRIFLUOROMETHYL)PHENYL-1-
(2-(4-TRIFLUOROMETHYL)PHENYL)ETHENYL)-2-PROPENYLIDENE)HYDRAZONE
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0207.HTM
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