Amdro (CASRN 67485-29-4)
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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 First 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 26-Week Dog Feeding American Cyanamid, 1980 |
NOEL: 0.33 mg/kg/day LEL: 1.0 mg/kg/day |
1000
|
1
|
3E-4
mg/kg/day |
* 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 Studies/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
Database — High
RfD — High
The chosen study provides sufficient data to rate a medium confidence. The database 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
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 amdro conducted in August 2003 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 — 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.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_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 RfC 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 |
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
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