Registration Dossier

Administrative data

Endpoint:
neurotoxicity: oral
Remarks:
other: 13 week neurotoxicity study/ subchronic study
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on study summary only.

Data source

Reference
Reference Type:
publication
Title:
Neurotoxic potential of ortho-, meta-, and para-cresol
Author:
Henck JW et al.
Year:
1987
Bibliographic source:
The Toxicologist 7, 246, No 983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was administered by gavage to 10 male and 10 female CD rats per dose group with 50, 175, 450 or 600 mg/kg bw/day for 13 weeks. Control group (20 male and 20 female rats) was administered only with corn oil. The following observations were performed: body weight gain, food consumption, clinical signs and signs of neurobehavioral toxicity.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Once a day for 13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 175, 450 or 600 mg/kg bw
Basis:
other: dissolved in corn oil
No. of animals per sex per dose:
Treatment group: 10 rats per sex/ dose
Control group: 20 rats per sex/ dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 50 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Dose dependent clinical signs of toxicity. However, it should be taken in account that only study abstract was available.
Remarks on result:
other:

Any other information on results incl. tables

Mortality:
control: 1/20 female
Compound-related mortality:
450 mg/kg bw/day: 1/10 males, 1/10 females;
600 mg/kg bw/day: 4/10 males, 7/10 females;
Mean Body weight development was not affected by treatment.
Mean food consumption: significant less in males of 450 and 600 mg/kg bw/day when compared to controls.
Dose-related clinical signs: salivation, myotonus, tremor, urine wet abdomen, hypoactivity, rapid respiration, myoclonus, low body posture, and labored respiration
Neurobehavioral toxicity:
High-dose group animals: tendency toward increased urination at study termination; incidence significantly greater than in controls: palpebral closure, rales, labored respiration
Pathology:
Brain weights comparable to controls
Gross and microscopic examination of tissues from control and treated animals showed no effects which were considered to be test substance treatment related.

Applicant's summary and conclusion