4,4',4''-(1-methylpropanyl-3-ylidene)tris[6-tert-butyl-m-cresol]

Endpoint summary

Description of key information

Key values determined by experimental study.
Oral LD50 > 5000 mg/kg bw
Dermal LD50 > 7940 mg/kg

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:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non standard study design but data are adequate to draw conclusion on toxicity.

Qualifier:

according to guideline

Guideline:

other: Not specified

GLP compliance:

not specified

Test type:

other: Not specified

Limit test:

yes

Species:

other: rat, guinea pig, dog

Strain:

other: albino rats, no data for guinea pig, beagle dog

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: unspecified

Vehicle:

other: maize oil, polyethylene glycol, beef suet

Details on oral exposure:

Rats
A single dose of 5 g/kg given dissolved in polyethylene glycol 300 to two groups of 5 male and 5 female albino rats. To investigate the influence of the solvent on the toxicity of Topanol CA, corresponding doses with either polyethylene glycol 300 or maize oil as solvent were given to groups of 3 female rats. Dose levels of 1 g/kg and 5 g/kg were used. In feeding trials preliminary to a 90-day study, groups of 5 male and 5 female rats were fed at concentrations of 5%, 1% and 0.2% w/w in the diet incorporated by dissolving an appropriate quantity of Topanol CA in maize oil.

Guinea pigs
In two groups of 5 male and 5 female guinea pigs receiving a single oral dose of 5 g/kg.

Dogs
A beagle bitch was given a dose of 2 g/kg as a 25% solution in polyethylene glycol. To a second bitch, the Topanol CA was given dissolved in beef suet, and the animal consumed an amount of food equivalent to a dose of approx. 3 g/kg.

Doses:

Rats
Dose levels of 1 g/kg and 5 g/kg were used. In feeding trials preliminary to a 90-day study, concentrations of 5%, 1% and 0.2% w/w in the diet incorporated by dissolving an appropriate quantity of Topanol CA in maize oil.

Guinea pigs
Single oral dose of 5 g/kg.

Dogs
2 g/kg as a 25% solution in polyethylene glycol. Substance dissolved in beef suet, and the animal consumed an amount of food equivalent to a dose of approx. 3 g/kg.

No. of animals per sex per dose:

Rats
Two groups of 5 male and 5 female albino rats
To investigate the influence of the solvent on the toxicity3 female rats
In feeding trials preliminary to a 90-day study, groups of 5 male and 5 female rats

Guinea pigs
Two groups of 5 male and 5 female guinea pigs

Dogs
two beagle bitches

Control animals:

not specified

Details on study design:

Rats
A single dose of 5 g/kg given dissolved in polyethylene glycol 300 to two groups of 5 male and 5 female albino rats. To investigate the influence of the solvent on the toxicity of Topanol CA, corresponding doses with either polyethylene glycol 300 or maize oil as solvent were given to groups of 3 female rats. Dose levels of 1 g/kg and 5 g/kg were used.
In feeding trials preliminary to a 90-day study, groups of 5 male and 5 female rats were fed at concentrations of 5%, 1% and 0.2% w/w in the diet incorporated by dissolving an appropriate quantity of Topanol CA in maize oil.
Guinea pigs
In two groups of 5 male and 5 female guinea pigs receiving a single oral dose of 5 g/kg.
Dogs
A beagle bitch given a dose of 2 g/kg as a 25% solution in polyethylene glycol. To a second bitch, the Topanol CA was given dissolved in beef suet, and the animal consumed an amount of food equivalent to a dose of approx. 3 g/kg.

Statistics:

no data

Preliminary study:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: rats

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Guinea pigs

Sex:

female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Dog

Mortality:

Rats
A single dose of 5 g/kg given dissolved in polyethylene glycol 300 to two groups of 5 male and 5 female albino rats caused no deaths.
To investigate the influence of the solvent on the toxicity of Topanol CA, corresponding doses with either polyethylene glycol 300 or maize oil as solvent were given to groups of 3 female rats. Dose levels of 1 g/kg and 5 g/kg were used. In the groups receiving 5 g/kg both showed signs of gastro-intestinal irritation within a few hours, the group given the Topanol CA in maize oil being much more severely affected. The group receiving Topanol CA in polyethylene glycol recovered completely in 24 hours. In the maize oil group one animal died at this interval after administration.
In feeding trials preliminary to a 90-day study, groups of 5 male and 5 female rats were fed at concentrations of 5%, 1% and 0.2% w/w in the diet incorporated by dissolving an appropriate quantity of Topanol CA in maize oil. In the 5% group the first animal died after 3 days and all of the remaining animals were dead within a week. A similar course of events was found in the animals fed at 1% and 7/10 animals died within the week.

Guinea Pigs
No deaths

Dogs
No deaths

Clinical signs:

other: Rats: A single dose of 5 g/kg dissolved in polyethylene glycol made the animals look in poor condition for some hours after administration. After 24 hours the animals had returned to normal and remained fit during the subsequent 10-day observation period.

Gross pathology:

Rats: In a group of rats given daily oral doses of 1 g/kg in polyethylene glycol for 10 consecutive days nothing abnormal was found on blood examination at the end of the period. No pathological changes were found at post mortem apart from quantities of white solid material in the gut lumen. Histopathological examination of tissue from the liver, kidney, lungs, pancreas, adrenals and representative portions of the alimentary tract revealed no abnormality.
In feeding trials preliminary to a 90-day study, post mortem showed inflammatory changes and haemorrhage were found in the mucosa of the stomach and small intestine, the adrenals were enlarged and patches of haemorrhage were found in the cortex on section. A similar course of events was found in the animals fed at 1% and 7/10 animals died within the week.
Guinea pigs: In two groups of 5 male and 5 female guinea pigs receiving a single oral dose of 5 g/kg, nothing abnormal was found at post mortem examination 10 days later and apart from some glycogen deficiency in the liver of 2 female animals, no pathological changes were found in tissue from the lungs, liver, kidney, pancreas, adrenals or representative portions of the gastro-intestinal tract.
Dogs: no data

Other findings:

With large doses, the appearance of the faeces suggests that much of a single dos remains unabsorbed in the gut. When given in a fatty solvent (maize oil) Topanol CA has an irritant effect on the gastro-intentinal tract but the toxicity of single doses is not greatly increased.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is not acutely toxic in all three species examined (rat, guinea pig, dog).

Executive summary:

The test substance was assessed by acute exposure in a combined study with three species, albino rat, guinea pig and beagle dog. With large doses, the appearance of the faeces suggests that much of a single dose remains unabsorbed in the gut. When given in a fatty solvent (maize oil) the substance has an irritant effect on the gastro-intentinal tract but the toxicity of single doses is not greatly increased.

No deaths occured due to acute exposure and the substance is considered non-toxic, with LD50 >5000 mg/kg in rats, >5000 mg/kg in guinea pigs and >3000 mg/kg in beagle dogs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

No dates referenced in the report

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The report is dated 1974 and no details of guidelines followed or detailed study plans are included.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

GLP compliance:

no

Test type:

other: Not stated

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Initial weight: Males: 2.5 - 2.7kg, Female: 2.3kg

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

Applied as a 40.0% suspension in corn oil.
No further details in report.

Duration of exposure:

24 hours

Doses:

5010mg/kg
7940mg/kg

No. of animals per sex per dose:

One male for each dosage. Female only used in higher dosage level.

Control animals:

not specified

Details on study design:

No details in the report.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 940 mg/kg bw

Based on:

test mat.

Mortality:

No mortalties recorded.

Clinical signs:

other: Reduced appetite and activity for two to three days.

Gross pathology:

No details recorded in the report.

Other findings:

Survivors (14 days) Viscera appeared normal.

ACUTE DERMAL TOXICITY                            New Zealand Albino Rabbits

	Dosage mg/kg	Initial Weight		Mortalities/Dosed			Time of Mortality
		Male	Female	Male	Female	Combined
1	5010	2.7	---	0/1	---	0/1
2	7940	2.5	2.3	0/1	0/1	0/2

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

LD50 > 7940 mg/kg

Executive summary:

New Zealand Albion rabbits received an application of 40.0% suspension in corn oil with an exposure time of 24 hours. Signs of intoxication included reduced appetite and activity for two to three days. No deaths were recorded and after 14 days the viscera appeared normal in all animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
Test standard not specified, however study report details study design and results are clear annd consice.
LD50 > 5000 mg/kg bw

Justification for selection of acute toxicity – dermal endpoint
Study is a read across to structural analogue.
LD50 > 7940 mg/kg

Justification for classification or non-classification

The data available for the substance demonstrate a lack of toxicity by acute exposure and above threshold levels that trigger classification.