4,6-bis(octylthiomethyl)-o-cresol

Endpoint summary

Description of key information

The test item is of low acute oral and dermal toxicity with an LD50 greater than 5000 mg/kg bw  for the oral route and an LD50 greater than 2000 mg/kg bw for the dermal route, as shown in valid guideline studies performed pursuant to OECD Guidelines 401 (Acute Oral Toxicity) and 402 (Acute Dermal Toxicity), respectively. Experimental data on acute inhalation toxicity is not available.

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Further description: F3-hybrid of RII 1/Tif x RII 2/Tif
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 173-195 (within ± 20% of mean value)
- Fasting period before study: overnight prior to dosing
- Housing: 5 per sex in Macrolon cage type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin).
- Diet: ad libitum; Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland),
- Water: ad libitum
- Acclimation period: 6 days
- Rationale for choice: The rat has been selected for this test as being a standard species for the determination of an acute oral LD50

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: mortality; daily; a.m. and p.m. on working days, a.m. on weekend days, clinical signs of toxicity; daily
- Frequency of weighing: on days 1, 7, and 14
- Necropsy of survivors performed: yes

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: No deaths occurred

Mortality:

No deaths occurred

Clinical signs:

other: Dyspnea, exophthalmos, ruffled fur, and curved body position were seen, beginning as early as 1 hour post dosing and lasting up to 10 day. The animals were fully recovered within 11 days.

Gross pathology:

No deviations from normal morphology were found.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf (SPF) hybrids of RII 1/Tif x RII 2/Tif (albino)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 216 - 270 g (within ± 20 % of mean value)
- Housing: caged individually in Macrolon cages type 3 with standardised soft wood bedding (Societe Parisienne des sciures, Pantin)
- Diet: ad libitum; Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland)
- Water: ad libitum
- Acclimation period: 22 days
- Rational for choice: the rat has been selected for this test as being a standard species for the determination of an acute dermal LD50.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- % coverage: no data
- Type of wrap if used: the test site was covered with a gauze-lined semi-occlusive dressing, which was fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: yes; with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg bw
- Concentration (if solution):undiluted

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: mortality; daily; a.m. and p.m. on working days, a.m. on weekend days, clinical signs of toxicity; daily
- Frequency of weighing: on days 1, 7, and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred

Clinical signs:

other: - Dyspnoea: starting 1 hour after dosing and lasting 5 days - Exophthalmoses: present 1 hour and 3 hours after dosing only - Ruffled fur: from 1 hour until day 9 after dossing - Abnormal body positions: ventral position (1 hour until day 1 after dosing) a

Gross pathology:

No deviations from normal morphology were found.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral Route of Exposure

In a limit test performed according to OECD Guideline 401 (Acute Oral Toxicity), groups of Tif: RAIf (SPF) rats (5 rats/sex/dose) were given a single oral dose (gavage) of the test article at a single dose of 5000 mg/kg bw. The animals were observed subsequently for a period of 14 days. No mortality occurred during the14-day observation period. Dyspnoea, exophthalmoses, ruffled fur, and curved body position were seen, beginning as early as 1 hour post dosing and lasting up to 10 days. The animals fully recovered within 11 days. At necropsy, no gross lesions were observed. As no deaths occurred in the study, the LD50 of the test article in rats is higher than 5000 mg/kg bw.

Dermal Route of Exposure

In a limit test performed according to the OECD Test Guideline 402, the test article was applied semi-occlusively for 24 hours to the shaved skin of five (7-8 weeks old) Tif: RAIf(SPF) albino rats per sex at a dose level of 2000 mg/kg bw. The animals were then observed for 14 days. No mortality was registered in the observation period. No local skin effects were observed at the application site. Treatment-related symptoms were dyspnoea, exophthalmoses, ruffled fur, and abnormal body position, which are common symptoms in acute tests. Additionally, sedation was found from three hours after the application up to day 1. All observed symptoms were reversible within 10 days after dosing. Necropsy revealed no gross abnormalities. As no deaths occurred in the study, the LD50 of the test article in rats is higher than 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.