6,6'-di-tert-butyl-4,4'-thiodi-m-cresol

Endpoint summary

Description of key information

Weight of evidence was applied for acute oral toxicity as Acute oral toxicity of 4,4'-Thiobis(6-tert-butyl-3-cresol) was tested in four independent experiments with male and female albino rats. In addition, acute dermal toxicity of 4,4'-Thiobis(6-tert-butyl-3-cresol) was tested in one study with male and female albino rats.

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:

weight of evidence

Study period:

1965

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is not performed under GLP conditions, used methods and results are preliminary documented

Qualifier:

no guideline available

Principles of method if other than guideline:

The diluted compound was fed by stomach tube to Sprague-Dawley strain albino male and female rats. After the approximate Minimum Lethal Dose was determined, groups of male and female rats were fed in increasing doses at increments of 0.1 fractional log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LD50 which was done according to a modification of the method of E. J. de Beer. Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined macroscopically.

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

1580, 2000, 2510, 3160 mg/kg bw

No. of animals per sex per dose:

5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 315 mg/kg bw

95% CL:

ca. 1 970 - ca. 2 730

Remarks on result:

other: Experiment 19

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 420 mg/kg bw

95% CL:

ca. 2 060 - ca. 2 845

Remarks on result:

other: Experiment 20

Clinical signs:

other: Toxic symptoms included severe diarrhea, marked weight loss, increasing weakness, and collapse.

Gross pathology:

At autopsy there was gastroenteritis, liver discoloration, and severe renal hyperemia.

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Conclusions:

A study in albino male and female rats suggested that Santonox was slightly toxic upon oral ingestion. The oral LD50 was placed at 2315 and 2420 mg/kg bw in two independent experiments. The study was not performed according to the general guidelines for acute toxicity testing under GLP conditions and poorly documented, since it dates from 1965. Nevertheless the data give an indication of acute toxicity upon oral administration to rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 315 mg/kg bw

Quality of whole database:

Three Klimisch 2 studies.

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:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is not performed under GLP conditions, used methods and results are preliminary documented.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

not mentioned.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: New Zealand

Sex:

male/female

Type of coverage:

not specified

Vehicle:

corn oil

Details on dermal exposure:

substance applied as a 40% solution-suspension in corn oil

Duration of exposure:

24 hours

Doses:

3160, 5010, 7940 mg/kg bw

No. of animals per sex per dose:

low: 1
middle: 2
high: 1

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 010 mg/kg bw

Clinical signs:

other: Reduced appetite and activity (three to seven days in survivors), increasing weakness, collapse, and death.

Gross pathology:

Lung hyperemia, liver discoloration, enlarged gall bladder, discoloration of spleen and kidneys, and gastrointestinal inflammation.

Other findings:

survivors (14 days): congestion of lungsand slight liver and kidney discoloration

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A study in albino male and female rabbits suggested that Santowhite crystals were toxic upon dermal administration. The dermal LD50 was placed at > 5010 mg/kg bw. The study was not performed according to the general guidelines for acute dermal toxicity testing under GLP conditions and poorly documented, since it dates from 1973. Nevertheless the data give an indication of acute toxicity upon dermal administration to rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 010 mg/kg bw

Additional information

None of the studies was performed according to the general guidelines for acute oral/dermal toxicity testing and neither was performed under GLP-conditions, since they were all rather old. Despite these short-comings, the data give an indication of acute oral/dermal toxicity in rats. Upon oral administration of 4,4'-Thiobis(6-tert-butyl-3-cresol) to rats, LD50's of 2315, 2345, 2420, 4150 mg/kg bw are reported. Upon dermal administration of 4,4'-Thiobis(6-tert-butyl-3-cresol) to rats, an LD50 of > 5010 mg/kg bw is reported.

Justification for selection of acute toxicity – oral endpoint

Three Klimisch 2 studies are available; this study was selected as the worst case as it provides the lowest LD50 value.

Justification for selection of acute toxicity – dermal endpoint

Only one study is available.

Justification for classification or non-classification

Based on the results of the acute oral/dermal toxicity studies, the substance does not need to be classified according to the CLP Regulation and Directive 67/548/EC.