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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and sufficient documented

Data source

Reference
Reference Type:
publication
Title:
Food flavourings and compounds of related structure. II.Subacute and Chronic Toxicity
Author:
Hagan EC, Hansen O, Fitzhug OG, Jenner PM, Jones WI, Taylor JM, Long EL, Nelson AA, Brouwer JB
Year:
1967
Bibliographic source:
Fd Cosmet Toxicol 5, 141-157

Materials and methods

Principles of method if other than guideline:
5 male and 5 female rats per group were fed 1000, 10000 ppm thymol in the diet (= ca. 67, 667 mg/kg bw/day) for 19 weeks.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Thymol (no data on purity)

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
19 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
1000, 10000 ppm food (= ca. 67, 667 mg/kg bw/day)
Basis:
nominal in diet
No. of animals per sex per dose:
5 male and 5 female rats/dose
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: no

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 667 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

10.000 ppm : no effects (indicates that there was no effect on growth or  
haematology, and no macroscopic or microscopic change in the tissues
1.000 ppm: (indicates that there was no effect on growth or haematology,
and no macroscopic change in the tissues, and that microscopic examination of the tissues was not performed.

Applicant's summary and conclusion

Executive summary:

5 male and 5 female rats per group were fed 1000, 10000 ppm ( 67, 667 mg/kg bw/d) thymol in the diet (= ca. 67, 667 mg/kg bw/day) for 19 weeks.

The rat'sweight, food intake and  general condition were recorded every week. Haematological examinationswere made at termination of subacute studies.
At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues ofall the rats were examined macroscopically at the time of sacrifice. The viscera were removed andthe liver, kidneys, spleen, heart and testes were weighed. These organs, the remaining adominaland thoracic viscera, and one hind leg, for bone, bone marrow and muscle, were preserved in 10%buffered formalin-saline solution for histopathological examination.
The NOAEL was 10.000 ppm (ca. 667 mg/kg bw/d); no effects (indicates that there was no effect on growth orhaematology, and no macroscopic or microscopic change in the tissues