Registration Dossier

Administrative data

repeated dose toxicity: other route
Adequacy of study:
other information

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
other: 96/54/EG, B.7; OECD 407 (1995)
GLP compliance:
Limit test:

Test animals

other: rat, HanIbm:WIST (SPF)

Administration / exposure

other: Miglyol 812 Neutralöl
Details on exposure:
Method of administration:
Duration of treatment / exposure:
Test duration: 28 days
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 100 mg/kg bw/day
Male: 5 animals at 300 mg/kg bw/day
Male: 10 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 100 mg/kg bw/day
Female: 5 animals at 300 mg/kg bw/day
Female: 10 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
Clinical observations:
One female treated with 1000 mg/kg/d was found dead on Day
16. Animals of this dose group showed treatment-related
clinical symptoms such as piloerection, increased
salivation, hunched posture (females only) and dyspnoea and,
possibly attributed to the bad taste of the test substance,
increased incidence of coprophagia and bedding consumption.
Neurofunctional testing battery revealed reduced mean
locomotor activity of animals treated with 1000 mg/kg/d.
During the first week of treatment period, the food
consumption was nonsignificantly lower in animals at this
dosage compared to the control values. The mean body weights
and body weight gain of males treated with 1000 mg/kg/d were
reduced during the treatment period (nonsignificantly) and
remained lower during the recovery phase (significantly).

Laboratory findings:
Males and females treated with 1000 mg/kg/d had increased
levels of total cholesterol, triglycerides and phospholipids
and increased activity of ALAT. Slightly higher globulin
levels were noted in females treated with 1000 mg/kg/d, and
the albumin/globulin ratio was slightly lower.

Urinalysis revealed incrased specific gravity of urine of
animals of the group that received 1000 mg/kg/d.

Effects in organs:
Treatment-related organ weigth changes were confined to
increased liver weights in males and females at 1000 mg/kg/d
at the end of study, that were reversible until the end of
the recovery period.

No treatment-related macroscopic findings were found,
microscopic lesions contributed to the test substance were
minimal to slight hepatocellular hypertrophy in central and
intermediate zones of the liver lobules; This effect has
been observed in males of all dose groups and in females of
the high dose group; its incidences increased with dosage.
After recovery, it decreased in severity and incidence, but
was still apparent at the end of this period.

The course of death of the spontaneously dying high dose
females could not be established.

Effect levels

Dose descriptor:
Effect level:
100.3 mg/kg bw/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Classified as: Not classified