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EC number: 203-253-7
CAS number: 104-93-8
In the chosen key study according to OECD TG 407 and GLP, oral administration of 4-methylanisole in olive oil in Wistar rats for 28 days (5 days/week) led to adverse effects on the liver and clinical symptoms, being a consequence of the irritating potential of the test substance. Under the experimental conditions chosen a NOEL of 100 mg/kg bw/d was determined for males and females for repeated dose toxicity after oral administration of the test material for 28 days.
In the chosen key study according to
OECD TG 407 and GLP,
4-methylanisole in olive oil was administered at doses of 100, 300 and
1000 mg/kg bw/d to 5 Wistar rats per sex and dose for 4 weeks (5
days/week) by gavage (BASF21C0810/89101). For comparison, 5 male and 5
female rats served as a vehicle control and were dosed with olive oil. Animals
receiving 1000 mg/kg bw/day 4-methylanisole showed clinical signs
(salivation, ataxia, tremor, laboured respiration). Clinical chemistry
revealed an increase in cholesterol in the females. Significantly
increased mean absolute and relative liver weights, accompanied with a
diffuse hypertrophy and single cell necrosis of hepatocytes in all male
and female rats was observed. The observed decreases in mean absolute
and relative spleen weights and decreases in mean relative thymus weight
in male rats as well as increases in mean absolute and relative kidney
weights in female rats lacked a histopathological correlate. In one male
rat, a focal hyperplasia and hyperkeratosis of the mucosa of the
forestomach was observed, being indicative for an irritating potential
of the test substance. In the
dose group of 300 mg/kg bw/d, some male and female animals showed
salivation after gavage of the test substance and a decreased mean
absolute spleen weights in male rats was observed, lacking a
histopathological correlate. Animals
receiving 100 mg/kg bw/d did not show any substance related changes.
The increase of the absolute and
relative liver weights, together with slight hypertrophy of the
hepatocytes and the occurrence of single cell necroses in both sexes at
a dose of 1000 mg/kg bw/d represents an adverse and treatment related
effect. However, changes in other organ weights were not considered to
be treatment related, since no histopathologic correlate was present, no
changes in the differential blood counts were observed and findings were
not observed for both sexes. The observed clinical symptoms are
considered a consequence of the irritating potential of the test
substance and are thus only a local, but not a systemic toxic effect.
This is confirmed by the fact, that in one male animal of the highest
dose group hyperkeratosis and focal hyperplasia were seen in the
forestomach. Under the experimental conditions chosen a NOEL of 100
mg/kg bw/d was determined for males and females for repeated dose
toxicity after oral administration of the test material for 28 days.
Further studies are available as short
summaries from secondary sources, which have not been chosen as key or
supportive studies (see IUCLID Chapter 7.5.):
In a subacute oral study in rats
similar to OECD TG 407, reported as short summary of results in a
publication, 10 (male/female) Wistar rats were treated daily for 28 days
with doses of 0, 40, 120 and 240 mg/kg bw/d via gavage (Brunsborg 1994). The
only adverse effects reported were decreases in serum creatinine and
urea in the mid and high dose group for both sexes and a decrease in the
packed cell volume in the mid and high dose group for males. However,
neither lowered total muscle mass, liver damage nor adverse effects on
the kidneys were reported in this study, serving as explanation for the
effects observed. Furthermore these findings were not confirmed in the
given key study, even at a limit dose of 1000 mg/kg bw/d.
In a dermal subacute range finding
study, reported as short summary in a database, 5 Sprague-Dawley rats
per sex and group were treated topically (semiocclusive) with
4-methylanisole (0, 66, 190, 700, 1000 mg/kg/day) as neat material or in
a 50% solution in diethylphtalate daily for 6 hours over a period of 14
days (Atkinson 1994).
Mortality, clinical signs, food and
water intake, body weight and skin reactions were monitored and blood
and urine samples were collected for urinalysis, hematology and clinical
chemistry screens. At the end of the application period, necropsy was
conducted, organ weights were determined and several tissues were
examined histologically (not further specified). After
application of the neat test material (i.e. 1000 mg/kg bw/d), all rats
were reported to be sacrificed on day 9 due to severe irritation. No
further adverse effects were reported. For the other dose groups, no
treatment related findings were reported, besides irritation at the test
site (not further specified).
The present data on repeated dose
toxicity do not fulfill the criteria laid down in 67/548/EEC and CLP,
and therefore, a non-classification is warranted.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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