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Paclobutrazol
CASRN 76738-62-0
Contents
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 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 NOEL: 250 ppm (diet) 1000 1 1.3E-2
weights, serum (12.5 mg/kg/day) mg/kg/day
cholesterol, hepatic
aminopyrine N- LEL: 1250 ppm (diet)
demethylase activity, (62.5 mg/kg/day)
and alanine
transaminase levels
90-Day Rat Feeding
Study
ICI Americas, Inc.,
1983a
*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 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
Data Base -- Medium
RfD -- Medium
The critical study is of good quality and is given a medium confidence rating.
Additional studies are supportive, but the data base on chronic toxicity is
incomplete; therefore, confidence in the data base 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
___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 -- 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.
_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 RfD 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
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)-
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0182.HTM
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