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

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1963

Report date:

1963

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Not specified

GLP compliance:

not specified

Test type:

other: Not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

217-420-7

EC Name:

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

Cas Number:

1843-03-4

Molecular formula:

C37H52O3

IUPAC Name:

4-[4,4-bis(5-tert-butyl-4-hydroxy-2-methylphenyl)butan-2-yl]-2-tert-butyl-5-methylphenol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Name of material: Topanol CA
Uses of material and estimated scale of production: To be used as a thermal stabiliser in polypropylene (up to 1.0% w/w in virgin polymer). 11,000 tons p.a. of stabilised polymer are expected to be manufactured, hence up to 110 tons p.a. of Topanol CA could be expected to be used.
In the present state of knowledge Topanol CA is by far the best agent for stability in this product (“Propathene”).
Physical state: fine powder
Colour: nearly white
Odour: faintly “organic”
Particle size: very small
Stability: stable
Solubility in water, acids, alkalis, vegetable and mineral oils and organic solvents: soluble in some organic solvents, polymers, etc.

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:

no data

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: rats

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Guinea pigs

Effect levels 3

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.

Applicant's summary and conclusion

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.