2-methylbutan-2-ol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only secondary literature (handbook)

Data source

Reference

Reference Type:

review article or handbook

Title:

Patty's Industrial Hygiene and Toxicology

Author:

Rowe and McCollister

Year:

1982

Bibliographic source:

Clayton and Clayton (eds.), Vol.2C, 3rd ed. (1982), John Wiley & Sons, New York, 4604 - 4605, 4608, 4701

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated dermal toxicity

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-methylbutan-2-ol

EC Number:

200-908-9

EC Name:

2-methylbutan-2-ol

Cas Number:

75-85-4

Molecular formula:

C5H12O

IUPAC Name:

2-methylbutan-2-ol

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male/female

Administration / exposure

Details on exposure:

Route of Administration: dermal, half of the dose was applied to the clipped backs of the rabbits twice a day.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0.344 or 3440 mg/kg bw/day
Basis:
no data

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

344 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: systemic toxicity

2

Dose descriptor:

LOAEL

Effect level:

344 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: local effects

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No adverse effects were detected in those animals that received the low dose other than the expected local effects to the skin at the site of application. These included erythema, drying, thickening, cracking and induration. The high dose caused similar but more extensive injury to the skin and caused serious systemic effects. Three animals of each sex became comatose and died or were sacrified in a moribund condition after a few applications. Gross and histopathologic examinations failed to reveal morphologic lesions that would account for the condition of these animals. With the exception of decreases in body size, adipose reserves, and glycogen of hepatocytes, all other parameters were within the normal range.

Applicant's summary and conclusion

Conclusions:

The repeated dermal toxicity of the test item to rats was tested in a subacute study. The NOEAL was determined to be 344 mg/kg bw/day.

Executive summary:

The repeated dermal toxicity of the test item to rabbits was tested in a subacute study. The animals were exposed over a period of 4 weeks with a frequency of 5 days per week. The test item was administrated by applying half of the doses to the clipped backs of the rabbits twice a day. 5 males and 5 females were exposed to a dose of 3440 mg/kg bw/day. Control animals were used, treated with the concurrent vehicle. The NOAEL (basis for effect level systemic toxicity) was determined to be 344 mg/kg bw/day. The LOAEL (basis for effect level local effects) was determined to be 344 mg/kg bw/day. No adverse effects were detected in those animals that received the low dose other than the expected local effects to the skin at the site of application. These included erythema, drying, thickening, cracking and induration. The high dose caused similar but more extensive injury to the skin and caused serious systemic effects. Three animals of each sex became comatose and died or were sacrified in a moribund condition after a few applications. Gross and histopathologic examinations failed to reveal morphologic lesions that would account for the condition of these animals. With the exception of decreases in body size, adipose reserves, and glycogen of hepatocytes, all other parameters were within the normal range.