Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key, rat, 19 weeks, feeding study, NOAEL (systemic) = 10000 ppm thymol in the diet (= ca. 667 mg/kg bw/day) (Hagan, 1967)

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
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
Limit test:
no
Specific details on test material used for the study:
Commercially-available materials, rather than pure chemicals, were used since the purpose of these studies was to evaluate the toxicity of these materials in relation to their use as food additives.
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: weanling
- Housing: individually in wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
19 weeks
Frequency of treatment:
daily via food
Dose / conc.:
1 000 ppm
Remarks:
1000 ppm nominal in diet (= ca. 67 mg/kg bw/day)

Dose / conc.:
10 000 ppm
Remarks:
10000 ppm nominal in diet (= 667 mg/kg bw/day)
No. of animals per sex per dose:
5 male and 5 female rats/dose
Control animals:
yes, plain diet
Details on study design:
Rationale for animal assignment (if not random): litter mates were used for the study
Post-exposure period: no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 3, 6, 12 and 22 months
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- Parameters checked examined: red cell counts, white cell counts, haemoglobins, haematocrits
Sacrifice and pathology:
GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
not examined
Details on results:
10000 ppm (667 mg/kg bw/d): no effect on growth or haematology, and no macroscopic or microscopic change in the tissues
1000 ppm ( 67 mg/kg bw/d): no macroscopic effect, thus histopathology not performed
Dose descriptor:
NOAEL
Effect level:
> 667 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
gross pathology
haematology
histopathology: neoplastic
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no

At the dose of 10000 ppm (667 mg/kg bw/d) there was no effect on growth or haematology, and no macroscopic or microscopic change in the tissues.

Conclusions:
The NOAEL was 10000 ppm (ca. 667 mg/kg bw/d); there was no effect on growth orhaematology, and no macroscopic or microscopic change in the tissues.
Executive summary:

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. The rat's weight, food intake and  general condition were recorded every week. Haematological examinations were made after 3, 6, 12 and 22 months. At the termination of the experiments the rats were sacrificed and exsanguinated. The tissues of all rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart and testes were weighed. These organs, the remaining abdominal and thoraic viscera, and one hind leg (for the examination of bone, bone marrow and muscle), were preserved in 10% buffered formalin-saline solution for histopathological examination. The NOAEL was 10000 ppm (ca. 667 mg/kg bw/d); there was no effect on growth or haematology, and no macroscopic or microscopic change in the tissues.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
667 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the repeated dose feeding study for 19 weeks no effects (indicates that there was no effect on growth or hematology, and no macroscopic or microscopic change is the tissue) at the highest applied dose (10000 ppm = 667 mg/kg bw/d) were seen (Hagan, 1967).

The gavage study (combined Repeat dose and Reproductive/Developmental toxicity screening test) (MHW Japan, 1996) revealed local effects with 40 mg/kg bw/d on the forestomach due to the corrosive properties of thymol, which were not seen in the 19 weeks oral feed study, where the test substance is incorporated in the feed matrix. Therefore for systemic effects the oral feed study was used and for local effects the gavage study, respectively.

Justification for classification or non-classification

Based on the available studies on repeated dose toxicity, it is concluded that the substance does not need to be classified according to Regulation (EC) No 1272/2008 for this hazard.