[1,1'-Biphenyl]-2-carbonitrile, 4'-methyl-

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not declared

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study was provided us by ECHA under the 12 years rule. Available data contain scanty study details: the limited amount of information and the lack of the full study report do not allow a proper reliability assessment.

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

EC 422-310-9 (identity was verified by ECHA while providing us with information in response to our inquiry)

IUPAC Name:

EC 422-310-9 (identity was verified by ECHA while providing us with information in response to our inquiry)

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: methylcellulose (0.5%)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Test duration: 28

Frequency of treatment:

7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
15 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
50 mg/kg bw/day
Basis:
actual ingested

Doses / concentrations 4

Remarks:

Doses / Concentrations:
150 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 15 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 150 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 15 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at150 mg/kg bw/day

Control animals:

yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

At intermediate (50 mg/kg) and high (150 mg/kg) doses, animals showed movement and postural disorders, piloerection, hair loss, and decrease in body weight.

In a dose-dependent manner, in all males and females a decrease in body weight and in food consumption was observed. In both males and females treated with the highest dose (150 mg/kg) and with the intermediate dose (50 mg/kg), water consumption was increased in the first two weeks of the study; the effect persisted in males.

In males treated with the highest dose (150 mg/kg) the following laboratory changes were observed: reduced alkaline phosphatase levels, increased AST levels, reduced beta-globulin, glucose, potassium, calcium and phosphate levels, increased albumin:globulin ratio. In females treated with the highest dose (150 mg/kg) the following laboratory changes were observed: reduced glucose levels, increased creatinine and BUN levels.

At intermediate (50 mg/kg) and high (150 mg/kg) doses, animals body weight was reduced. In 1 female in the intermediate dose group and in 1 female in the high dose group, uterus size was reduced: micorscopic examination confirmed the presence of moderate atrophy.

In treated animals, absolute and relative weights of epidydimes, prostate, seminal vesicles and ovaries were reduced. Other organs showed changes (increase or reduction) in their absolute and relative weight. In all dosage groups, micorscopic examination showed signs of chronic myocarditis in both males and females, and degeneration of tubular epitelium in males testes. Histopathological examination was not performed for the other sexual organs nor for ovaries.

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

According to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, study results indicate that the substance should be classified as following for its effects after repeated exposure:
- DSD: T R48/25, Xn R62
- GHS: STOT RE 1 H372, Repr 2 H361