Thymol

Endpoint summary

Description of key information

The endpoint 'Acute toxicity' is waived based on the classification as Skin Corr. 1B (H314). As supporting information several studies are available for the oral route and one study is available for the dermal route. The key results of these studies are as follows:

oral

Acute, oral, rat, LD50 = 980 mg/kg bw (Jenner, 1964)

dermal

Acute, dermal, rat, LD50 > 2000 mg/kg bw (Bomhard, 1986)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: sufficient documented for evaluation

Principles of method if other than guideline:

Groups of 10 young adult Osborne-Mendel rats evenly divided by sex were fastened for approximately 18 hr prior treatment. Animals had access to water at all times, and the food was replaced in cages as soon as animals received their respective doses. All doses were given by intubation. All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks. LD50's were computed by the method of Lichtfeld & Wilcoxon (1949), J.Pharmacol. 96, p.99.

GLP compliance:

no

Test type:

other: no data

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Doses:

no data

No. of animals per sex per dose:

10

Control animals:

not specified

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

980 mg/kg bw

Mortality:

Death time: 4 hr-5 days.

Clinical signs:

other: Toxic signs: Depression, ataxia, coma on high doses

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

EU GHS

Conclusions:

LD50 = 980 mg/kg bw.

Executive summary:

Method: 10 male and female rats received thymol as a 20% solution in propylene glycol per gavage.

Result: LD50 = 980 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

980 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according guideline 84/449/EWG

Guideline:

other: Directive 84/449/EWG

Principles of method if other than guideline:

Method: other: Directive 84/449/EWG

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Thymol 99.5/99.6 % (peak area)

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

male and female Wistar rats, SPF, average weight 210 g (males) and 197 g (females), animals were housed in macrolon cages type II

Type of coverage:

occlusive

Vehicle:

other: Cremophor

Details on dermal exposure:

substance was individually prepared on an aluminium foil, mixed with cremophor and fixed on the animals by means of plaster

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

animals were inspected daily for clinical signs
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing before application, after 1 week and and at the end of the observation period of 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

not necessary (limit test)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality

Clinical signs:

other: no symptoms of poisoning

Gross pathology:

no findings

Other findings:

a brownish discoloration on skin areas was observed at the application side on some animals

mortality: 0/10; no pathological changes (post observation time 14 days). After a single dose of 2000 mg/kg no signs of intoxication were observed. The application area showed a brownish discoloration  concerning 3 male and 2 female rats. The discoloration exists up to 4 days.

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

results: LD50 > 2000 mg/kg bw; no pathological changes and no signs of intoxication were observed

Executive summary:

method: 2000 mg/kg bw of the test substance was applied occlusive for 24 h on 5 male and 5 female rats.

Post observation time was 14 days

results: LD50 > 2000 mg/kg bw; no pathological changes and no signs of intoxication were observed

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The endpoint 'Acute toxicity' is waived based on the classification as Skin Corr. 1B (H314). As supporting information several studies are available for the oral route and one study is available for the dermal route.

oral

For rats an LD50 = 980 mg/kg bw was identified (Jenner 1964), for mice the LD50 ranged from 640 mg/kg bw (Izeki, 1956) to 1800 mg/kg bw (McOmie, 1949) in several studies. For guinea pigs an LD50 of 880 mg/kg bw was determined (Jenner 1964).

dermal

For acute dermal toxicity an LD50 > 2000 mg/kg bw was found; in this study no pathological changes and no signs of intoxication were observed (Bomhard, 1986).

Justification for classification or non-classification

Based on the available data, the registered substance is classified for lethal effects following a single oral exposure as Acute Tox Cat. 4 (H302) according to Regulation (EC) No 1272/2008. This outcome also correlates with the harmonised CLP classification of thymol for acute toxicity (H302).