Propargite (CASRN 2312-35-8)
view QuickView

0296
Propargite; CASRN 2312-35-8
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 Propargite
File First On-Line 05/01/1990
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 05/01/1990 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
Last Revised — 05/01/1990
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 |
---|---|---|---|---|
No adverse effects observed at the HDT 2 Year Dog Feeding Study Uniroyal Chemical, 1966 |
NOEL: 900 ppm (22.5 mg/kg/day) LEL: None |
1000
|
1
|
2E-2
mg/kg/day |
Reduced body weight gain; increased resorption; reduced body weight; delayed ossification Rabbit Developmental Toxicity Study Uniroyal Chemical, 1982 |
NOEL: 2.0 mg/kg/day (Maternal and Fetotoxic) LEL: 6.0 mg/kg/day (Maternal and Fetotoxic) |
100
|
1
|
2E-2
mg/kg/day |
*Conversion Factors: 1 ppm = 0.025 mg/kg/day (assumed dog food consumption) Actual dose tested for the developmental toxicity study
__I.A.2. Principal and Supporting Studies (Oral RfD)
Uniroyal Chemical. 1966. MRID No. 00076402. Uniroyal Chemical. 1982. MRID No. 00105990. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Four male and four female purebred beagle dogs were fed Omite for 2 years at 0, 100, 300, and 900 ppm (0, 2.5, 7.5, and 22.5 mg/kg/day) (Uniroyal Chemical, 1966). Growth and food intake were comparable to the control group. No adverse effects were observed by hematology, blood chemistry determinations or urine examinations. Gross postmortem examination failed to reveal any dose- related effects. No significant microscopic changes in the tissues and organs were observed. The NOEL for systemic toxicity is equal to or greater than 900 ppm (22.5 mg/kg/day) (HDT).
The test material was administered orally by intubation from day 6 through day 18 of gestation to 4 groups of 17 pregnant female rabbits at dose levels of 2, 6, 10, and 18 mg/kg/day (Uniroyal Chemical, 1982). Test group dosages were prepared as a suspension in corn oil. Another group of 17 female pregnant rabbits served as control and received corn oil vehicle only. A dose-related pattern of decrease in body weight gain in females was noted at 6 mg/kg/day and above and was statistically significant in the highest group (18 mg/kg/day). Lower survival of pregnant and nonpregnant females was observed at 10 and 18 mg/kg/day. The fetuses showed delayed ossification at 6 mg/kg/day and above; this was considered related to maternal toxicity of the test compound. Fetotoxicity was also evidenced by increased resorptions and reduced fetal body weight at 6 mg/kg/day and reduced fetal viability at 10 and 18 mg/kg/day. Therefore, based on the above effects the NOEL for maternal toxicity and fetotoxicity is 2 mg/kg/day.
__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 for the use of either the chronic dog or rabbit developmental NOELs. An additional UF of 10 was used on the dog NOEL to account for the uncertainties in the other chronic studies and uncertainties created by effects observed in the developmental toxicity studies, making uncertain the determination of the most sensitive toxicological endpoint.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
The NOELs for developmental effects in both rats and rabbits are lower than
the dog NOEL also chosen to establish the RfD. However, the developmental
toxicity studies are difficult to interpret because of the irritating
properties of the chemical and the gavage nature of the exposure. Thus,
the
work group felt the need to list both the chronic dog study and the rabbit
developmental toxicity study as co-critical. Identical RfDs are derived.
Data Considered for Establishing the RfD
1) 2-Year Feeding - dog: Principal study - see previous description; core
grade minimum (Uniroyal Chemical, 1966)
2) Developmental toxicity - rabbit: Co-critical study - see previous
description; core grade minimum (Uniroyal Chemical, 1982)
3) 2-Year Feeding (oncogenic) - rat: Dietary levels tested: 0, 100, 300,
900,
and 2000 ppm (0, 5, 15, 45, 100 mg/kg/day); Twenty-five male and 25 female
weanling rats of the FDRL strain were fed propargite at 0, 100, 300 and 900
ppm for 2 years and 2000 ppm for 1.5 years. Fifteen rats/sex were used as
controls. No dose-related responses were disclosed by hematology, blood
chemistry determinations, or urinalysis. Scattered instances of lower mean
body weight gains at weeks 26 through 104 were noted in females receiving
diets of 100, 300, and 900 ppm when compared with control values. However,
the mean body weight gain for females in all treated groups was about 6%
reduced to 104 weeks of the study when compared with the control values which
appears not to be statistically significant. At 74 weeks the mean body
weights of rats fed 2000 ppm (HDT) was significantly reduced for both males
and females. This group also consumed less food and had a lower mean body
weight gain when compared with the control group. The LEL for systemic
toxicity is 2000 ppm (100 mg/kg/day) based on significantly reduced mean body
weights. Therefore, the NOEL for systemic toxicity is 2000 ppm (45
mg/kg/day)
(HDT); core grade supplementary (Uniroyal Chemical, 1966)
4) 3-Generation Reproduction - rat: Dietary levels tested: 0, 100, and 300
ppm (0, 5, and 15 mg/kg/day); Groups of 25 male and 25 female rats were
fed 0 or 100 ppm for one generation. The dose of the treatment group was then
increased to 300 ppm for the next two generations. The study results
revealed no significant effects on either fertility or reproductive performance.
Neonatal viability and lactation efficiency as evidenced by the survival and
growth of the young rats from birth to weaning were comparable with the
control group. Mean body weight of the pups was also comparable with that
of the control group. The NOEL for reproductive toxicity is equal to or
greater than 300 ppm (15 mg/kg/day) (HDT); core grade supplementary (Uniroyal Chemical, 1966)
5) Developmental toxicity - rat: Dietary levels tested: 0, 6, 25, and 105
mg/kg/day; propargite was administered by gavage to pregnant rats from day 6
through day 15 of gestation. An increase in mortality was observed in
parental animals at 105 mg/kg/day (HDT). Therefore, the NOEL and LEL for
maternal toxicity are 25 and 105 mg/kg/day, respectively. An increased
incidence of missing sternebrae was observed at 25 mg/kg/day. Therefore,
the NOEL and LEL for fetotoxicity are 6 and 25 mg/kg/day, respectively. No
teratogenic effects were noted at any dose tested; core grade minimum
(Uniroyal Chemical, 1979a)
Other Data Reviewed:
1) 18-Month Feeding (carcinogenicity - mouse: Dietary levels tested: 0,
50, 160, 500, and 1000 ppm (0, 7.5, 24, 75, and 150 mg/kg/day); 60 male and 60
female albino CD-1 mice/dose group were administered propargite for 18
months. Observations of the animals daily for 18 months revealed no untoward effects
toward food consumption, body weights, hematology, and survival. Variable
organ weight changes in the kidney, adrenal, and uterus were not supported by
any pathology in these organs. The NOEL for systemic is greater than or
equal to 1000 ppm (150 mg/kg/day) (HDT); core grade minimum (Uniroyal Chemical,
1979b)
2) 90-day Feeding - dog: Dietary levels tested: 2000 to 2500 ppm (0, 50 to
62.5 mg/kg/day); Male and female beagle dogs were administered propargite at a
dietary level from 2000 to 2500 ppm for 90 days. Signs of apparent
compound effects among the test dogs were decreased appetite and body weight loss.
The test animals were comparable with the controls in appearance, behavior,
elimination, results of clinical laboratory studies, organ weights, organ/body
weight ratios, and gross necropsy findings. The NOEL for systemic toxicity
is less than 2000 ppm (50 mg/kg/day) based on decreased appetite and body weight
loss; core grade supplementary (Uniroyal Chemical, 1968)
3) 90-Day Feeding - rat: Dietary levels tested: 0, 10, 20, 40, 100, and
200 mg/kg/day; Propargite was administered to 5 groups of weanling albino rats
consisting of 5 males and 5 females each for 90 days. A control group of
15 males and 15 females was used and received no treatment. Clinical
examination including hematological and blood chemistry examinations disclosed no
abnormalities. Growth was retarded at the 100 mg/kg/day group and to a
greater extent in the 200 mg/kg/day group. Marked reduction in absolute
organ weights in the 200 mg/kg/day group was observed. Gross microscopic
examination of liver, kidneys, adrenal, and gonads of the rats disclosed no
significant abnormalities in any of the treated groups. The LEL for
systemic toxicity is 100 mg/kg/day based on retarded growth. Therefore, the NOEL for
systemic toxicity is 40 mg/kg/day; core grade minimum (Uniroyal Chemical, 1964)
Data Gap(s): Chronic Rat Feeding Study, Rat Reproduction Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical studies are of adequate quality and are given medium confidence ratings. Because of the lack of two adequate chronic studies (rat feeding and reproduction studies), 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
Source Document — This assessment is not presented in any existing U.S. EPA document.
Other EPA Documentation — Pesticide Registration Standard, April 1986; Pesticide Registration Files
Agency Work Group Review — 08/19/1986, 04/15/1987, 03/23/1988
Verification Date — 03/23/1988
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 propargite 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 — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
iSubstance Name — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
Last Revised — 05/01/1990
_VI.A. Oral RfD References
Uniroyal Chemical. 1964. MRID No. 0007641. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1966. MRID No. 00076402. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1968. MRID No. 00036285. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1979a. MRID No. 00041386. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1979b. MRID No. 00130942. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
Uniroyal Chemical. 1982. MRID No. 00105990. 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 — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
Date |
Section |
Description |
---|---|---|
05/01/1990 | 1.A. | Oral RfD Summary on-line |
05/01/1990 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory Action Section on-line |
04/01/1997 | III, IV, V. | Drinking Water 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
Substance Name — Propargite
CASRN — 2312-35-8
Primary Synonym — Omite
Last Revised — 05/01/1990
- 2312-35-8
- comite
- cyclosulfyne
- D014
- ENT 27226
- Naugatuck D014
- Omite
- omite 57 E
- omite 85 E
- propargil
- Propargite
- sulfurous acid, 2-[4-(1,1-dimethylethyl)phenoxy] cyclohexyl 2-propynyl ester
- sulfurous acid, 2-(p-tert-butylphenoxy)cyclohexyl 2-propynyl ester
- 2-(p-tert-butylphenoxy)cyclohexyl propargyl sulfite
- 2-(p-tert-butylphenoxy)cyclohexyl 2-propynyl sulfite
- Uniroyal D014