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EC number: 202-705-0
CAS number: 98-83-9
Reliable studies are available for oral application as well as for exposure via inhalation.Oral (MHW Japan, 1997):Study design according to OECD Guideline No. 422NOEL: 40 mg/kg bwLOAEL: 200 mg/kg bw (based on histological changes in liver and kidneys of both sexes and in thymus of female rats; increase in GPT in male rats)Inhalation (rats & mice; NTP, 2007)Study design comparable to OECD Guideline No. 413NOAEL: 150 ppm for males (based on kidney & liver weights)Inhalation (several species; Wolf et al., 1956)6 months, 7h/d, 5d/weekNOAEL: 200 ppm (based on kidney & liver, reduction in growth)Dermal:For the dermal route there are no data available. However, as inhalation is the most important route of exposure and for this endpoint a recent NTP study in rats and mice is available, no dermal repeated dose toxicity study is considered to be needed or scientifically justified.
In this study performed according to OECD Guideline
422, alpha-methylstyrene was given to SD (Crj:CD) rats of both sexes at
dose levels of 0, 40, 200 or 1000 mg/kg/day by oral administration for
43 days from 14 days prior to mating to days after mating in males and
for the periods including 14 days prior to mating and from gestation
period, followed by delivery until post-partum day 3 in females.
At 1000 mg/kg, male rats showed a suppression of
body weight gain, and a decrease in food consumption, and one animal
died due to ischuria with urinary calculi. Female rats showed slight
suppression of body weight gain in the late gestation period.
Histopathological examination demonstrated increases of liver and kidney
sizes, acidophilic change of hepatocytes and increase of fatty droplets
in the fascicular zone of the adrenals in both sexes, increase of
hyaline droplets and basophilic change in the renal tubular epithelium,
formation of urinary calculi and hyperplasia of the mucosal epithelium
in the urinary bladder in male rats, and vacuolation and infiltration of
lymphocytes in the renal tubular epithelium and atrophy of the thymus in
female rats. Blood chemical examination in male rats showed increases in
GPT, urea nitrogen and potassium, and a decrease in triglyceride.
At 200 mg/kg, similar histological changes were
found in the liver and kidneys of both sexes, and the thymus of female
rats, and an increase in GPT was observed in male rats. Haematological
examination showed that the test substance had no effects in males.
The LOAEL for repeated dose toxicity was 200
mg/kg/day. The NOEL was given with 40 mg/kg/day for both sexes.
In this study (design comparable to OECD Guideline
413), groups of 10 male and 10 female rats were exposed by whole-body
inhalation to alpha-methylstyrene at concentrations of 0, 75, 150, 300,
600 or 1000 ppm for 6 hrs per day and 5 days per week for 14 weeks.
Additional clinical pathology groups of 10 male and 10 female rats were
exposed to the same concentrations for 23 days. All rats survived to the
end of the study, and mean body weights of all exposed groups were
similar to those of the chamber controls. Kidney weights were
significantly increased in 1000 ppm males and at >= 600 ppm females.
Statistically significant increases in liver weights occurred at >= 150
ppm males and at >= 600 ppm females. The incidences of renal hyaline
droplet accumulation were similar between exposed groups and chamber
control groups, but the severity of hyaline droplet accumulation in >=
600 ppm males was greater than in chamber controls. Consistent with the
hyaline droplet accumulation, an exposure related increase in
alpha2u-globulin was detected in the kidneys of males exposed to
alpha-methylstyrene. Morphologic changes were not detected in the liver.
From this study a NOAEL of 300 ppm for male rats
was derived, based on effects relevant for human health risk assessment.
In this study (design comparable to OECD Guideline
413), groups of 10 male and 10 female B6C3F1 mice were exposed by
whole-body inhalation to alpha-methylstyrene at concentrations of 0, 75,
150, 300, 600 or 1000 ppm for 6 hrs per day and 5 days per week for 14
Two females in the 1000 ppm group died before
exposure on day 3. Final mean body weights of >= 600 ppm males and 75,
300, and 1000 ppm females were significantly less than those of the
chamber controls; final mean body weight gains of mice exposed to >= 300
ppm were also significantly less. Moderate to severe sedation (males
only) and ataxia were observed at 1000 ppm. The absolute liver weights
of >= 600 ppm females and the relative liver weights of >= 300 males and
females were significantly increased. The oestrous cycle lengths of >=
600 ppm females were significantly longer than that of the chamber
controls. Minimal to mild centrilobular hypertrophy was present in the
livers of males and females at >= 600 ppm. The incidences of
exposure-related nasal lesions, including atrophy and hyperplasia of
Bowman’s glands and atrophy and metaplasia of the olfactory epithelium,
were significantly increased in all exposed groups of males and females.
The incidences of hyaline degeneration, characterized by the
accumulation of eosinophilic globules in the cytoplasm of the
respiratory epithelium, were significantly increased in females at >=
The findings in mice at the respiratory epithelium was not considered to
be relevant for human health risk assessment. The effects observed in
liver weight at 300ppm did not lead to effects in histopathology or
clinical chemistry. Therefore, a NOAEL of 300 ppm has been derived.
In further inhalation studies several species were exposed for approx. 6
months to vapour 7h/d, 5d/week).
At 200 ppm no toxic effects were noted, while effects such as changes in
organ weights or slight growth depression were noted at >= 600 ppm. A
concentration of 3000 ppm caused severely increased mortality. The
NOAEL was reported to be 200 ppm (984 mg/m3). This study was used by
SCOEL to derive an OEL.
Based on the current findings there is no
indication of a specific target organ with relevance to human health.
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