Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
other: Repeated dose (28 days) Toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 June to 18 July 2001
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
acetone
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 days/week
No. of animals per sex per dose:
6

Results and discussion

Effect levels

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Dose descriptor:
NOAEL
Effect level:
9.9 mg/kg bw/day (nominal)
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
93.2 mg/kg bw/day (nominal)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Veterinary/clinical examination did not reveal any treatment-related findings. There were no treatment-related clinical signs and pre-terminal deaths observed in any of the tested doses. Ophthalmological and neurological examination did not reveal any treatment related abnormalities. The mean body weights and the net body weight gains were lower than their concurrent control group throughout treatment period at high dose and high dose recovery groups. During recovery period, the higher body weight gains were observed only at high dose recovery males. Significantly lower food intake was observed throughout the treatment period except on week 3 at high dose and on week 1 at high dose recovery males and at high dose recovery females.

Haematology: There were no treatment-related haematological changes observed at any of the tested doses in both sexes. Clinical chemistry: Biochemical investigations revealed significantly higher creatinine level and lower cholesterol level at high dose was dose correlated. Decreased levels of serum cholesterol are described in connection with hyperthyroidism. Histopathological examination of the thyroids did not reveal any change. The higher level of creatinine may be correlated to higher incidences of hyaline droplets-tubular epithelium and basophilic tubules and were reversible as there were no changes observed in the recovery group.

The absolute and relative weight of liver were significant higher in mid and high dose males and there was a dose correlated significant increase in mid and high dose females. The relative weight of liver was significantly higher in recovery groups in both sexes. The absolute and relative weight of kidneys was significantly higher in mid dose males with a significant increase in the relative weight of kidneys in high dose males and high dose recovery females. These changes were considered reversible and treatment related. There were no treatment related gross pathological changes. Histopathologically, hyaline droplets-tubular epithelium in the kidneys at mid and high dose males was considered to be a treatment-related reversible change. Hepatocellular hypertrophy in liver at high dose males and females and vacuolation - cortical cells in adrenals at high dose males were considered a physiological response to the xenobiotic.

Applicant's summary and conclusion