Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure is comparable to an official guideline.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Comparative toxicity of cresol isomers
Author:
Dietz DD, Levine BS, Sonawane RB, Rubenstein R, DeRosa C
Year:
1988
Bibliographic source:
the Toxicologists 7, 246 No.982
Reference Type:
other: ECHA disseminated dossier
Title:
not applicable
Author:
not applicable
Year:
2014
Bibliographic source:
ECHA disseminated dossier
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Sontag JM, Page NP, Saffotti U, NCI, DHEW Publication No (NIH)78-801Guidelines for Carcinogen Bioassay in small rodents
Deviations:
no
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 5-6 weeks
- Fasting period before study: 24 hours
- Housing: individually
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72
- Humidity (%): 50
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: test solution was produced on a weekly basis
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
During test week 1, 2, 4, 8 and 13
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 175, 600 mg/kg bw/day in corn oil
Basis:
actual ingested
No. of animals per sex per dose:
30 animals /sex/dose
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily for mortality and clinical signs

BODY WEIGHT: Yes
- Time schedule for examinations: day 1 and then weekly

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes , weekly

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: during quarantine period and in test week 13

HAEMATOLOGY: CLINICA CHEMISTRY : Urinalysis Yes
- Time schedule for collection of blood: as baseline clinical pathology, at test week 7 (interim kill) at study termination
- How many animals: 10 rats/sex/dose
- Parameters checked : see section "additional information on materials and methods"


NEUROBEHAVIOURAL EXAMINATION: No data
Statistics:
One-Way Analysis of Variance tests, Dunnett's t test.

Results and discussion

Results of examinations

Details on results:
At 600 mg/kg bw/day: mortality 19/30 females and 9/30 males,

Body weight:
reduction
body weight of females were unaffected
600 mg/kg bw/d, males: significant during week 2 through 10
175 mg/kg bw/d, males: significant during week 2

Treatment-related depression of the central nervous system: lethargy, dyspnoe, tremor and/or convulsions, recovering within 1 h after dosing

No effects on clinical chemistry, hematology, urinalyses parameters,
No treatment-related ophthalmic lesions,
No effects on organ weights,
No treatment-related gross and histomorphologic lesions

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: >= 175 mg/kg bw/day animals revealed central nervous system depression and showed statistically significant reduction in body weight and body weight gain.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion