Chemical U.S.A. Petition
for the Establishment of Tolerances on Imported Grapes and
Pesticide petition PP 3E6545. According
to this petition:
There are no registered uses of benthiavalicarb-isopropyl
in the U.S. and no other
tolerance petitions have been submitted to EPA for this active
ingredient. Dietary exposure is limited in the U.S. to residues
imported grapes and tomatoes and their processed components.
in or on the raw IMPORTED
processed commodities juice
processed commodities wine
and developmental toxicity
a 2-generation reproduction study in Sprague Dawley rats
receiving 0, 100, 1,000 or 10,000 ppm benthiavalicarb-isopropyl
in the diet, the parental no observed adverse effect level
(NOAEL) was 100 ppm based on hepatocyte
hypertrophy at the next higher dose level. The reproductive
NOAEL was 10,000 ppm.
In a developmental toxicity study in
New Zealand White rabbits
receiving 0, 10, 20 or 40 mg/kg/day benthiavalicarb-isopropyl
from day 6 to 28 of gestation, the maternal
NOAEL was 20 mg/kg/day based on
abortion and increased liver
weights at the 40 mg/kg/day dose. The
developmental NOAEL was 20 mg/kg/day based on increased
incidence of small fetus and delayed ossification of the hindlimb
talus at 40 mg/kg/ day.
In a developmental toxicity
study in Sprague Dawley rats
receiving 0, 10, 100 or 1,000 mg/kg/day from day 7 to day
19 of gestation, the
maternal NOAEL was 10 mg/kg/day based on elevated liver
and adrenal weights at 100 mg/kg/day.
The NOAEL for developmental toxicity was 1,000 mg/kg/day.
In the 13-week feeding study with mice,
the dose levels were 0, 50, 200, 7,000, or 20,000 ppm. The
NOAEL was 200 ppm (equivalent to 33.0 mg/kg/day and 45.2 mg/kg/day
in males and females, respectively, based on
systemic toxicity of decreased body weights, anemias, and
generalized liver toxicity at 7,000
In the 3 month dog feeding
study the dose levels were 0, 40, 200, or 1,000 mg/kg/day.
The NOAEL was 40 mg/kg/day based on hematological
and clinical chemistry changes, organ weight changes and the
findings of hepatocyte hypertrophy and pigmentation in the
spleen at 200 mg/kg/day.
In a chronic/oncogenicity study Fisher
rats received 0, 50, 200, 5,000, or 10,000 ppm of benthiavalicarb-
isopropyl for up to 104 weeks. The NOAEL was 200 ppm (9.9
mg/kg/day and 12.5 mg/kg/day in males and females respectively),
based on a variety of toxic effects,
primarily in the liver and kidney, and adenocarcinomas of
the uterus at 5,000 ppm.
In an oncogenicity study
in mice, the dietary doses were 0, 20, 100, 2,500 or
5,000 ppm. The NOAEL was 100 ppm (13.7 mg/kg/day and 18.6
mg/kg/day in males and females, respectively) based on
a variety of toxic effects, primarily in the liver and kidney,
and hepatocellular blastoma and carcinoma at
In a 52-week study with
Beagle dogs, the dietary dose levels were 0, 4, 40,
or 400 mg/kg/day. The NOAEL was 40 mg/kg/day based on increased
liver weights in males and females at
Numerous supplemental mechanistic studies in
the rodent were carried out to further elucidate the mechanisms
involved in tumor formation in the lifetime rodent studies.
These studies indicated that benthiavalicarb-isopropyl
behaves like a promotor following initiation with diethylnitrosamine
(DEN), and does not have initiating activity.
The compound did not cause oxidative damage in studies on
rat or mouse liver, was a slight enzyme
inducer, and did not cause hepatocyte proliferation.