2-methylbutan-2-ol

Endpoint summary

Description of key information

Repeated inhalation toxicity: The repeated inhalation toxicity of the test item to rats was determined. he animals were exposed to doses of 150, 500 and 1500 ppm equivalent to doses of 0.54, 1.8 and 5.4 mg/L. No NOAEL value was determined. Minor effects were observed. Animals exposed to the highest concentration exhibited motor incoordination after the first two exposures but not after seven exposures, suggesting that some tolerance may have occurred. 
Repeated dermal toxicity: The repeated dermal toxicity of the test item to rabbits was determined. The NOAEL value was determined to be 344 mg/kg bw/day. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: only secondary literature (handbook)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: Repeated inhalation toxicity

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

7 days

Frequency of treatment:

6 hour/day

Remarks:

Doses / Concentrations:
150, 500 or 1500 ppm (0.54; 1.8; 5.4 mg/L)
Basis:
no data

No. of animals per sex per dose:

8 animals/dose and control.

Control animals:

yes, concurrent no treatment

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

Other examinations:

Organ weights: Yes

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not specified

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:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Critical effects observed:

not specified

Animals exposed to the highest concentration exhibited motor incoordination after the first two exposures but not after seven exposures, suggesting that some tolerance may have occurred. They appeared lethargic for 3 to 4 hours after exposure. There was an increase in both absolute and relative liver and kidney weights and a decrease in blood glucose level; gross pathologic examination did not reveal any consistent changes attributable to exposure

Conclusions:

The repeated dose toxicity (inhalation) of the test item on rats was examined. Minor effects were observed. Animals exposed to the highest concentration exhibited for example motor incoordination after the first two exposures but not after seven exposures, suggesting that some tolerance may have occurred. No NOAEC was determined.

Executive summary:

The repeated dose toxicity (inhalation) of the test item was examined. Rats were exposed to the test item over a period of 7 days with a frequency of 6 hours per day. 8 animals per dose and control were used. The animals were exposed to doses of 150, 500 and 1500 ppm equivalent to doses of 0.54, 1.8 and 5.4 mg/L. Control animals were not treated. As a result animals exposed to the highest concentration exhibited motor incoordination after the first two exposures but not after seven exposures, suggesting that some tolerance may have occurred. They appeared lethargic for 3 to 4 hours after exposure. There was an increase in both absolute and relative liver and kidney weights and a decrease in blood glucose level; gross pathologic examination did not reveal any consistent changes attributable to exposure. No further information are available.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

only secondary literature (handbook), no NOAEL identified

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

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)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated dermal toxicity

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Sex:

male/female

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

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

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

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

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

Critical effects observed:

not specified

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

344 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Quality of whole database:

only secondary literature (handbook)

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

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)

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated dermal toxicity

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Sex:

male/female

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

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

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

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

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

Critical effects observed:

not specified

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

344

Study duration:

subacute

Species:

rabbit

Quality of whole database:

only secondary literature (handbook)

Additional information

Repeated dose toxicity (inhalation)

The repeated dose toxicity (inhalation) of the test item was examined. Rats were exposed to the test item over a period of 7 days with a frequency of 6 hours per day. 8 animals per dose and control were used. The animals were exposed to doses of 150, 500 and 1500 ppm equivalent to doses of 0.54, 1.8 and 5.4 mg/L. Control animals were not treated. As a result animals exposed to the highest concentration exhibited motor incoordination after the first two exposures but not after seven exposures, suggesting that some tolerance may have occurred. They appeared lethargic for 3 to 4 hours after exposure. There was an increase in both absolute and relative liver and kidney weights and a decrease in blood glucose level; gross pathologic examination did not reveal any consistent changes attributable to exposure. No further information are available.

Repeated dermal toxicity

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.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Only study available

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Only study available

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Only study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation according to Annex VI of Regulation (EC) 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result and according to the harmonised Annex VI classification the substance is considered not to be classified for repeated dose toxicity under Regulation (EC) No 1272/2008.

Self-Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the results the substance is considered not to be classified for repeated dose toxicity under Regulation (EC) No 1272/2008.