(S)-α-hydroxy-3-phenoxy-benzeneacetonitrile

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

441-070-6

EC Name:

-

Cas Number:

61826-76-4

Molecular formula:

C14H11NO2

IUPAC Name:

(2S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

- PREPARATION OF DOSING SOLUTIONS:
The preparations of the test substance were made freashly every day shortly before the administration to the animals. The dosing volume was 1 mL/kg bw

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

once a day, 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Negative control

Doses / concentrations 2

Dose / conc.:

5 mg/kg bw/day (nominal)

Remarks:

Low dose

Doses / concentrations 3

Dose / conc.:

16 mg/kg bw/day (nominal)

Remarks:

Mid dose

Doses / concentrations 4

Dose / conc.:

50 mg/kg bw/day (nominal)

Remarks:

High dose

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Dose selection rationale: the selection of the doses was based on the results of a dose range finding study.

Positive control:

N.A.

Results and discussion

Results of examinations

Details on results:

- Mortality:
There was no test substance related mortality
- Observations in life, clinical and functional observations:
In high dosed animals, "digging in the bedding material", a sign, indicating unpleasant sensations, was noted frequently after test substance administration
- Body weights and feed consumption:
In the third week of dosing, feed consumption of high dosed females was statistically significantly lower than in the controls. Except for this, no significant differences were noted in body weights and feed consumption
- Hematology and clinical chemistry:
There were no statistically significant differences between a dosed group and the controls
- Organ weights
Liver and spleen were statistically significantly increased in high dose females
- Necropsy
There were no test substance related alterations noted
- Recovery groups
There were no test substance related alterations until the end of the recovery group

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

16 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Organ weights

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In an oral short-term repeated dose toxicity study conducted according to OECD guideline 407, rats were treated with 5, 16 and 50 mg/kg bw/day once a day, 7 days per week for a total of 28 days. Based on the results, the NOEL can be considered to be 16 mg/kg bw/day.

Executive summary:

In an oral short-term repeated dose toxicity study conducted according to OECD guideline 407, rats were treated with 5, 16 and 50 mg/kg bw/day once a day, 7 days per week for a total of 28 days. Based on the results, the NOEL can be considered to be 16 mg/kg bw/day. No classification is warranted according to CLP regulation 1272/2008.