Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has been presented to ECHA in the framework of a NONS notification. The document is now public because presented more than 12 years ago. The summary received is from migrated NONS dossier

Data source

Reference
Reference Type:
other: body responsible for the test
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
refer to confidential details on test material
IUPAC Name:
refer to confidential details on test material

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: deionised water
Details on oral exposure:
gavage tube
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 days/week
No. of animals per sex per dose:
Male: 5 animals at 0 mg/kg bw/dayMale: 5 animals at 40 mg/kg bw/dayMale: 5 animals at 200 mg/kg bw/dayMale: 5 animals at 1000 mg/kg bw/dayFemale: 5 animals at 0 mg/kg bw/dayFemale: 5 animals at 40 mg/kg bw/dayFemale: 5 animals at 200 mg/kg bw/dayFemale: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:
No mortalities occurred. In the high-dose group, red discoloration of the urine was observed as from the 4th day of testing and red discoloration of the hairless parts of the body as from the 20th day of testing.Haematologically, it was not possible to establish any differences from the controls.Clinico-chemically, changes in the form of a significant reduction in the creatine values and the alpha 1-globulin values occurred in particular among the females from the high-dose group.In addition, the adrenal weights (absolute and relative) were clearly elevated among the males from the high-dose group as were the relative liver weights of the females from the medium and high-dose groups and the relative kidney weights in the high-dose group.Macroscopically, a slight red discoloration of kidneys was diagnosed among the females as from 40 mg/kg and among the males as from 200 mg/kg. In the high-dose group, all of the animals exhibited clear red discoloration of the kidney, the stomach and the connective tissue and, among the males, of the testes and of the intestine too.Pathohistologically, dose-dependent deposits of the test substance were found in the tubular epithelium of the kidneys of the animals from the medium and high-dose groups, something which was interpreted as reabsorption of dye particles and lysosomal accumulation. All of the other findings were not dose-related and correspond to the spontaneous pathological picture for the age group of the species.

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 200 mg/kg bw/day (nominal)
Basis for effect level:
other: original NCD unit is mg/kg/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The substance was tested for repeated oral toxicity following OECD 407. Under the experimental conditions the NOAEL is 200 mg/kg bw /day.
Executive summary:

The substance was tested for repeated oral toxicity following OECD 407. Under the experimental conditions the NOAEL is 200 mg/kg bw /day.