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EC number: 203-742-5
CAS number: 110-16-7
WoE. Fitzhugh 1947. Repeated dose toxicity: oral, diet, rats, 2 years: no NOEL or LOEL defined, lowest dose 0.5 % in feed, corresponding to ca. 250 mg/kg bw and dayWoE. Humiston 1975 (maleic anhydride). Repeated dose toxicity: oral, diet, rats, 90 days: LOEL = 100 mg/kg bw and dayWoE. Humiston 1975a (maleic anhydride). Repeated dose toxicity: oral, diet, rats, 90 days: NOEL = 40 mg/kg bw and dayWoE. Humiston 1977 (maleic anhydride). Repeated dose toxicity: oral, diet, rats, 183 days: LOEL = 250 mg/kg bw and dayWoE. CIIT 1983 (maleic anhydride). Repeated dose toxicity: oral, diet, rats, 2 years: LOEL = 32 mg/kg bw and day, NOEL = 10 mg/kg bw and daySS. Humiston 1975b (maleic anhydride). Repeated dose toxicity: oral, diet, dogs, 90 days: NOEL = 60 mg/kg and day
Maleic anhydride was mixed with the
food and administered on 7 day/week ad lib., for 2 years to Fischer 344
rats. Doses were 0, 10, 32 or 100 mg/kg body weight. 126 animals were
used per group.
interim termination timepoints were at 6, 12, and 18 months with final
study termination at 24 months. Clinical
signs of toxicity, body weights and food consumption were monitored and
extensive histopathological examinations were conducted. Additionally,
the eyes of all animals were examined by ophthalmoscope and hematology,
clinical chemistry and urine parameters were assessed in five
analysis of the diet for maleic anhydride was conducted 2 to 4 years
after completion of the in-life phase of the study. A
sample of each diet was removed, refrigerated or frozen for future
chemical determination of the concentration of maleic anhydride. The
GC-MS measurements were (on average of random samples) 69-75% of the
expected for male and female diets, respectively. There
was a problem with the animal room lighting control system which
resulted in exposure to continuous light for an unknown period.
There was only marginal toxicity which
was evidenced by small (<6%), but dose-related, decrease in body weights
of male rats fed 32 and 100 mg/kg/day compared to the controls. The
female rats fed 32 and 100 mg/kg/day also had reduced body weights, but
the reductions were smaller and of shorter duration than those observed
in males. Food consumption was also slightly reduced during limited
periods during the study for animals in the mid- and high-dose
groups. Neither neurologic nor ophthalmologic evaluations revealed
differences between treated and control animals. There was a high
incidence of cataracts in the animals of this study, with 100% of the
animals examined at 18 month and at study termination bearing
cataracts. The severity of these cataracts was independent of maleic
anhydride consumption. Hematology, clinical chemistry, gross or
histopathological evaluations (including the kidneys) showed no
differences between treated and control animals that were considered
related to maleic anhydride exposure.
LOEL was defined to be 32 mg/kg/day and the NOEL was 10 mg/kg/day for
Results from various subchronic and chronic
toxicity studies with maleic acid and maleic anhydride in rats and dogs
with oral administration are available. Reported LOELs were between 32
and 250 mg per kg body weight and day, depending on study designs.
Reported NOELs were 10 and 40 mg per kg body weight and day in rats and
60 mg per kg body weight in Beagle dogs.
No classification is derived from the
results of the studies available.
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