Paclobutrazol (CASRN 76738-62-0)
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0182
Paclobutrazol ;
CASRN 76738-62-0
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 Paclobutrazol
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 01/01/1992 |
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 — Paclobutrazol
CASRN — 76738-62-0
Last Revised — 01/01/1992
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 |
---|---|---|---|---|
Elevated liver 90-Day Rat Feeding ICI Americas, Inc., |
NOEL: 250 ppm (diet) (12.5 mg/kg/day) LEL: 1250 ppm (diet) (62.5 mg/kg/day) |
1000
|
1
|
1.3E-2
mg/kg/day |
*Dose Conversion Factors & Assumptions: 1 ppm = 0.05 mg/kg/day (assumed rat food consumption)
__I.A.2. Principal and Supporting Studies (Oral RfD)
ICI Americas, Inc. 1983a. MRID No. 00132689; HED Doc. No. 003813. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
Four groups of Wistar rats (20/sex/dose level) were fed diets containing 0,
50, 250 or 1250 ppm of paclobutrazol for 90 days. At 1250 ppm liver weights
were elevated in females along with serum cholesterol, hepatic aminopyrine N-
demethylase activity, and alanine transaminase levels. The lowest dose tested
was 50 ppm. No effects were seen in male rats.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — Based on a subchronic exposure study, an uncertainty factor of 1000 was
used to account for inter- and intraspecies differences and for the
insufficient duration of the study to fully assess chronic effects.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
None
Data Considered for Establishing the RfD:
1) 90-Day Feeding - Rat: Principal study - see previous description; core
grade minimum
2) 1-Year Feeding - Dog: NOEL=15 mg/kg/day; LEL=75\mg/kg/day (increased liver
weight, increased serum alkaline phosphatase and triglyceride levels,
increased hepatic aminopyrine N-demethylase activity, and enlarged
hepatocytes); core grade minimum (ICI Americas, Inc., 1984a)
3) 6-Week Oral Dosing - Dog: NOEL=15 mg/kg/day (LDT); LEL=75\mg/kg/day (at
doses of 75 and 225 mg/kg dogs had increased liver weights and serum alkaline
phosphatase levels, only one male and one female dog were tested at each
dose); core grade supplementary (ICI Americas, Inc., 1983b)
4) Teratology - Rat: Maternal NOEL=40 mg/kg/day (LDT); Maternal LEL=100
mg/kg/day (slight decrease in body weight gain and food utilization
efficiency; 250 mg/kg/day caused mortality (5/24), liver enlargement, and
pallor of the liver); Fetotoxic NOEL not established; Fetotoxic LEL=40
mg/kg/day (LDT); (increased incidence of delayed ossification in fetuses; the
250 mg/kg/day dose induced cleft palate in three fetuses from two litters.);
core grade supplementary (ICI Americas, Inc., 1983c)
5) Teratology - Rat: Maternal NOEL=100 mg/kg/day (HDT); Fetotoxic NOEL=10
mg/kg/day; Fetotoxic LEL=40 mg/kg/day (hydronephrosis, hydroureter, delayed
ossification, minor skeletal defects); core grade minimum (ICI Americas, Inc.,
1984b)
6) Teratology - Rabbit: Maternal NOEL=25 mg/kg/day; Maternal LEL=75\mg/kg/day
(decreased body weight gain); Fetotoxic NOEL=125 mg/kg/day (HDT) (low
fertility with only the mid- and low-dose groups having the minimum number of
animals required); core grade supplementary (ICI Americas, Inc. 1983c)
Data Gap(s): Chronic Rat Feeding Study; Rat Reproduction Study; Rabbit
Teratology Study
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Medium
RfD — Medium
The critical study is of good quality and is given a medium confidence rating. Additional studies are supportive, but the database on chronic toxicity is incomplete; therefore, confidence in the database can be considered medium to low. Confidence in the RfD can also be considered medium to low.
__I.A.6. EPA Documentation and Review of the Oral RfD
Pesticide Registration Files
Agency Work Group Review — 09/02/1986
Verification Date — 09/02/1986
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 Paclobutrazol 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 — Paclobutrazol
CASRN — 76738-62-0
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Paclobutrazol
CASRN — 76738-62-0
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 — Paclobutrazol
CASRN — 76738-62-0
Last Revised — 01/01/1992
_VI.A. Oral RfD References
ICI Americas, Inc. 1983a. MRID No. 00132689; HED Doc. No. 003813. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
ICI Americas, Inc. 1983b. MRID No. 00132690; HED Doc. No. 003813. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
ICI Americas, Inc. 1983c. MRID No. 00132693; HED Doc. No. 003813. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
ICI Americas, Inc. 1983d. MRID No. 00132692; HED Doc. No. 003813. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
ICI Americas, Inc. 1984a. MRID No. 00132691, 00143166; HED Doc. No. 003813,
004352. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
ICI Americas, Inc. 1984b. MRID No. 00143158; HED Doc. No. 004352. 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 — Paclobutrazol
CASRN — 76738-62-0
Date |
Section |
Description |
---|---|---|
01/01/1992 | I.A.4. | Citations added |
01/01/1992 | VI. | Bibliography 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 — Paclobutrazol
CASRN — 76738-62-0
Last Revised — 03/31/1987
- 66346-04-1
- 76738-62-0
- 77108-06-6
- Cultar
- ICI-PP 333
- Paclobutrazol
- PP 333
- 1H-1,2,4-Triazole-1-ethanol-.beta.-((4-chlorophenyl)methyl)-.alpha.-(1,1-dimethylethyl)-