Iso(C10-C14)alkyl (3,5-di-tert-butyl-4-hydroxyphenyl)methylthioacetate

Endpoint summary

Description of key information

The LD50 value derived from the acute oral toxicity study with the test substance is > 2000 mg/kg bw. The dermal LD50 is > 2000 mg/kg bw. 

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

Study period:

1988-02-08 to 1988-04-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, GLP

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: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd., Animal Production, 4332 Stein / Switzerland
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 174 to 196 g
- Fasting period before study: Prior to dosing, the animals were fasted overnight
- Housing: Segregated by sex, group-housed (5 animals per cage) in Macrolon cages type 4, with standardized soft wood bedding
- Diet: Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2°C
- Humidity: 55 +/- 10%
- Air changes: 15 air changes/h
- Photoperiod: 12 hour/ day light cycle

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: daily
Body weight: at start and on days 7 and 14
- Necropsy of survivors performed: yes
The animals were submitted to a gross necropsy at the end of the observation period

Statistics:

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Ruffled fur, dyspnea, hunched posture, and exophthalmos were seen, being common symptoms in acute tests. The animals recovered within 10 days.

Gross pathology:

No deviations from normal morphology were found.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Executive summary:

The toxic effects of the test substance (described in section 1.2) in albino rats (Tif: RAI f (SPF)) were investigated in an acute toxicity study according to OECD Guideline 401 and in compliance with GLP. Ten albino rats (5 males and 5 females) were treated with the test item at a dosage level of 2000 mg/kg bw by gastric intubation (gavage). Following the single treatment, the animals were observed for a period of 14 days. A gross necropsy was performed on all animals. There were no deaths. Ruffled fur, hunched posture, exophthalmos and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 10 days. All rats remained healthy and gained weight by day 14 of the study. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 of the test item is greater than 2000 mg/kg bw in male and female rats when orally applied.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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

Study period:

1988-02-04 to 1988-03-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, GLP

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: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd., Animal Production, 4332 Stein / Switzerland
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 230 to 255 g
- Housing: Segregated by sex, group-housed (5 animals per cage) in Macrolon cages type 4, with standardized soft wood bedding
- Diet: Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2°C
- Humidity: 55 +/- 10%
- Air changes: 15 air changes/h
- Photoperiod: 12 hour/ day light cycle

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of the rat
- % coverage: 10 % of the body surface
- Type of wrap if used: Gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was cleaned with lukewarm water at the end of the exposure period

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: daily;
Signs and symptoms: daily for 14 days;
Body weight: at start and on days 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:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Ruffled fur, dyspnea, abnormal body positions, and reduced spontaneous activity were seen, being common symptoms in acute tests. The animals recovered within 7 days.

Gross pathology:

No deviations from normal morphology were found.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Executive summary:

The toxic effects of the test substance (described in section 1.2) in albino rats (Tif: RAI f (SPF)) were investigated in an acute dermal toxicity study according to OECD Guideline 402 and in compliance with GLP. Ten albino rats (5 males and 5 females) were treated with the test item at a dosage level of 2000 mg/kg bw. The test substance suspension was evenly dispersed on the skin (10 % of the body surface area). It was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage. After an exposure period of 24 hrs the dressing was removed and the skin was cleaned with lukewarm water. Thereafter the skin reaction was appraised repeatedly. A gross necropsy was performed on all animals. There were no deaths. All rats remained healthy and gained weight by day 14 of the study. No irritations were noted on any of the test sites. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 of the test item is greater than 2000 mg/kg bw in male and female rats when topically applied.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral route:

The toxic effects of the test substance in albino rats (Tif: RAI f (SPF)) were investigated in an acute oral toxicity study according to OECD Guideline 401 and following GLP principles. Ten albino rats (5 males and 5 females) were treated with the test item at a dose level of 2000 mg/kg bw by gastric intubation (gavage). Following the single treatment, the animals were observed for a period of 14 days. A gross necropsy was performed on all animals. There were no deaths. Ruffled fur, hunched posture, exophthalmos and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 10 days. All rats remained healthy and gained weight by day 14 of the study. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 of the test item is greater than 2000 mg/kg bw in male and female rats when orally applied (Ciba-Geigy, 1988).

This result is supported by a second acute toxicity study following OECD test guideline 401. Five male and female rats were treated by gavage with the test substance at dose levels of 1000, 2500, 5000 and 7500 mg/kg body weight. No mortalities were observed at 1000 mg/kg. At 2500 mg/kg, 1 male and 1 female animal died. At the next higher dose of 5000 mg/kg, 2 males and 1 female died. All animals died in the high dose at 7500 mg/kg. The LD50 was calculated at 4128 mg/kg bw and 4721 mg/kg bw for males and females, respectively (Ciba-Geigy, 1983).

Inhalation route:

The oral and dermal routes of exposure are assessed by key acute toxicity studies. An additional assessment for the inhalation route is not required according to section 2 of REACH Annex VIII (Regulation 1907/2006/EC).

Dermal route:

The toxic effects of the test substance in albino rats (Tif: RAI f (SPF)) were investigated in a GLP compliant acute dermal toxicity study according to OECD Guideline 402. Ten albino rats (5 males and 5 females) were treated with the test item at a dose level of 2000 mg/kg bw. The test substance suspension was evenly dispersed on the skin (10 % of the body surface area). It was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage. After an exposure period of 24 hrs the dressing was removed and the skin was cleaned with lukewarm water. Thereafter the skin reaction was appraised repeatedly. A gross necropsy was performed on all animals. There were no deaths. All rats remained healthy and gained weight by day 14 of the study. No irritations were noted on any of the test sites. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 of the test item is greater than 2000 mg/kg bw in male and female rats when topically applied (Ciba-Geigy, 1988).

Justification for selection of acute toxicity – oral endpoint
GLP-compliant guideline study.

Justification for selection of acute toxicity – dermal endpoint
GLP-compliant guideline study.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the data, classification for acute toxicity is not warranted under Directive 67/548/EEC.

 

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.