2-methylbutan-2-ol

Endpoint summary

Description of key information

Pentanol-isomeres have been reported to cause respiratory irritation (MAK scientific documentation on Pentanol-Isomers, 2008) 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1968-11-05 to 1968-11-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study predating guidelines and GLP, but scientifically fully acceptable.

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

other: BASF test (close to Draize test), occlusive, 2 rabbits (+2 for 20h exposure and ear-skin test), intact skin; 1,5 or 15 minutes or 20h exposure

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.88 kg (male); 2.58 kg (male);
no body weight from additional two animals

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: From: 1968-11-05 To: 1968-11-13

Type of coverage:

occlusive

Preparation of test site:

other: exposure on back and ear

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

undiluted (2 mL / animal)

Duration of treatment / exposure:

1, 5 or 15 minutes
20 hours (20h data selected as worst case instead of non existing 4 h test)

Observation period:

The animals were observed 8 days.

Number of animals:

4 rabbits

Details on study design:

TEST SIDE
-Area of exposure: two rabbits at six sites per animal along the dorsum
Two additional rabbits: two sites per animal (plus left ear, not considered)
-% coverage: approximately 6 cm2 each

REMOVAL OF TEST SUBSTANCE
- Washing: yes, mild detergent (50% Lutrol)


SCORING SYSTEM: Draize score (converted from recorded grading with detailed instructions provided by data owner)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24h, 48h, 72h (mean)

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Exposure duration 20h(instead of 4h, OECD 404)

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24 h, 48h, 72h (mean)

Score:

0

Max. score:

4

Remarks on result:

other: Exposure duration 20h(instead of 4h, OECD 404)

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24h, 48h, 72h (mean)

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Exposure duration 20h(instead of 4h, OECD 404)

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24h, 48h, 72h (mean)

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72h

Remarks on result:

other: Exposure duration 20h(instead of 4h, OECD 404)

Irritant / corrosive response data:

mean erythema / edema scores per animal below 2.3: not irritating

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1968-10-02 to 1968-10-16

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study predating guidelines and GLP, but obtained by standardised procedures comparable to those presently in use and thus valid for characterising the toxicity of the substance tested.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation:
Animal 1: male, 2.45 kg
Animal 2: female, 2.37 kg
Animal 3: male, 2.5 kg
Animal 4: male, 2.33 kg

ENVIRONMENTAL CONDITIONS
- no data

IN-LIFE DATES: From: 1968-10-02 To: 1968-11-16

Vehicle:

unchanged (no vehicle)

Controls:

other: control eye: left eye of same animal

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.05 mL of undiluted test item (corresponds to about 40.3 mg test item)

CONTROL MATERIAL
- Amount applied: 0.05 mL of "NaCl" (probably physiol. saline solution)

Duration of treatment / exposure:

not applicable - eye not rinsed after 24 hours

Observation period (in vivo):

8 days (readings at 1h, 24h and 8d after application)

Number of animals or in vitro replicates:

three male, one female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize score (converted from recorded grading with detailed instructions provided by data owner)

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 120h (mean)

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 7 days (euthanised due to devel. staphylom)

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 120h (mean)

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: 24, 48 and 72h (mean)

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 120h (mean)

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 120h (mean)

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

other: 24, 48 and 72h (mean)

Score:

0

Max. score:

4

Remarks on result:

other: scores of 3 before and after standard readings, but fully reversible within 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 120h (mean)

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days (euthanised due to devel. staphylom)

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 120h (mean)

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

other: 24, 48 and 72h (mean)

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 120h (mean)

Score:

0.67

Max. score:

2

Reversibility:

not fully reversible within: 7 days (euthanised due to devel. staphylom)

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h (mean)

Score:

0

Max. score:

2

Remarks on result:

other: No 72h and 96h readout in raw data

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72h (mean)

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 6 days

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: 24, 48 and 72h (mean)

Score:

0

Max. score:

2

Irritant / corrosive response data:

Instillation of undiluted test item caused slight to marked conjunctival irritation with swelling of the lids and occasional bleeding.
In one case, a staphylom developed and the rabbit was euthanised. Corneal opacity was found to be marked to severe.
A slight iritis was occasionally observed. Not all effects were reversible within the maximum observation period of 8 days.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a skin irritation study (BASF AG, 1968), two Vienna White rabbits were exposed to 2 mL on the dorsum (occlusive treatment, approximately 6 cm²of the body surface area) with the undiluted test item for 1, 5 or 15 minutes. In addition, two further animals were treated for 20 hours. The observation period was 7 to 8 days. Irritation was scored at first by a grading system of the data owner, converted later into the Draize scoring system. As a worst case, data were limited to the two rabbits exposed for 20 hours. Moderate signs of skin irritation (mean erythema: 2 both animals; mean edema: 1.3 and 0) were noted after a 20 h exposure period in both animals at the 24h, 48h and 72h readings. The effect was fully reversible within 6 to 8 days. Under the conditions of this study, the test item is not a dermal irritant.

 

In a second skin irritation study (Rowe and MCollister, 1982) rabbits which were repeatly treated with the test item to the uncovered skin demonstrated no irritation. In case the skin of the animals was covered with a cloth, redness and exfoliation resulted. Confinement of the material under an impervious covering resulted in severe necrosis. The study results point towards skin irritation potential when the substance is repeatly and semiocclusively applied to rabbit skin. Since there is no further information on the study available the reliability could not be assigned (Klimisch 4).

 

Eye irritation

In an eye irritation key study (BASF, 1968), 0.05 mL (appr. 40.3 mg) of test item was instilled into the conjunctival sac of the right eye of four Vienna White rabbits (three males/one female). Eyes were not washed. Animals were observed for 8 days. Readout were performed at 24, 48 and 120 hours. Irritation was scored at first by a grading system of the data owner, converted later into the method of Draize. Instillation of undiluted test item caused slight to marked conjunctival irritation with swelling of the lids and occasional bleeding (mean conjunctivae score: 2,1,2.33 and 2.67, respectively; mean chemosis score: 1.33, 2.33, 1 and 0, respectively). In one case, a staphylom developed and the rabbit was euthanised. Corneal opacity was found to be marked to severe (mean cornea score: 3, 1.67, 2.33 and 3, respectively). A slight iritis was occasionally observed (mean iris score: 0.67, 0, 0.67 and 0, respectively). One animal showed the effects, which triggered the chemosis, conjunctivae and iris score, even at the end of the observation period and thus, indicated a non-reversible eye irritation. 

 

In a second eye irritation study in rabbits (Rowe and McCollister, 1982) the instilled undiluted test substance caused pain, moderate conjunctival irritation with swelling of the lids, moderate to severe corneal cloudiness, and moderate iritis subsequent to instillation. The effects were fully reversible within 14 days post exposure but not after 7 days. No further study details are available.

Justification for selection of skin irritation / corrosion endpoint:
Most reliable study

Justification for selection of eye irritation endpoint:
Most reliable study

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results obtained in the skin irritation study (BASF AG, 1968) 2 -Methylbutan-2 -ol has not to be classified and labelled for skin irritation according to Directive 67/548/EEC (DSD) and according to Regulation (EC) No 1272/2008 (CLP). However, a second study (Rowe and McCollister, 1982) pointed towards skin irritation potential after repeated exposure. According to Regulation (EC) No 1272/2008 Annex VI Table 3.1 and Table 3.2 2 -Methylbutan-2 -ol is classified as skin irritating category 2, H315 and Xi, R38, respectively. Following a conservative approach the classification according Regulation (EC) No 1272/2008 Annex VI is adopted.

Based on the results obtained in the eye irritation study 2 -Methylbutan-2 -ol was classified as Xi, R41 (risk of serious damage to eyes) according to Directive 67/548/EEC (DSD). According to Regulation (EC) No 1272/2008 (CLP) 2 -Methylbutan-2 -ol has to be classified and labelled as eye irritating category 1, H318 (Irreversible effects on the eye).

According to Regulation (EC) No 1272/2008 Annex VI Table 3.1 and Table 3.2 2 -Methylbutan-2 -ol is classified as STOT SE 3, H335 and Xi, R37, respectively.