Isobutyl acetate

Endpoint summary

Description of key information

For isobutyl acetate, no valid data on irritation / corrosion could be located.
To compensate for this lack of data, information resulting from n-butyl acetate as supporting substance (structural analogue) are used as substitute.
No irritating effects in any of the rabbits tested could be observed in a primary skin irritation test similar to OECD TG 404.
In the rabbit eye, only slightly irritating effects were observed in a primary eye irritation test similar to OECD TG 405 and no classification is required.
There is no need to classify isobutyl acetate for respiratory irritation, based on data available for n-butyl acetate.

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:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Was not conducted under GLP but has sufficient data for interpretation of results. Read-across hypothesis: for details please see read-across report in IUCLID section 13

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: commercial available diet, ad libitum
- Water: municipal water, ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4-hour contact

Observation period:

up to 10 days after 4 hour contact period.

Number of animals:

6 (3 males and 3 females)

Details on study design:

READING TIMES: 1 hour, 24 hour, and 2, 3, 7 and 10 days after 4 hour contact period.

SCORING SYSTEM: Method of Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable as no effect has been observed

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable as no effect has been observed

Irritant / corrosive response data:

none.

Other effects:

One animal was found dead at 10 days from unknown causes, but most probably not treatment-related.

None.

Read-across justification: for details please see read-across report in IUCLID section 13

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study n-butyl acetate was not irritating to the skin of rabbits.

Executive summary:

A 4 -hour occlusive treatment of 6 rabbits (3 males and 3 females) with 0.5 mL of the n-butyl acetate similar to OECD TG 404 did not induce any erythema nor edema, therefore the test item does not reveal any irritating potential under the conditions tested (DCC/BRRC, 1987).

This study was judged to be reliable (RL2) and therefore was selected as key study (read-across from supporting substance).

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:

year of publication: 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles Read-across hypothesis: for details please see read-across report in IUCLID section 13

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single exposure (no washing indicated in report)

Observation period (in vivo):

up to 14 days

Number of animals or in vitro replicates:

4

Details on study design:

READING TIMES: 24, 48 and 72 h as well as 7 and if required 14 days after instillation of test material

SCORING SYSTEM: according to OECD TG 405 (Draize-Scores)

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #3 each

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect observed

Irritation parameter:

cornea opacity score

Basis:

animal: #2 and #4 each

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not relevant since no effect observed

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #1, #2, #3, and #4 each

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not relevant since no effect observed

Irritation parameter:

chemosis score

Basis:

animal: #2, #3 and #4 each

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

Corena score was 0 at any time for animal #1 and #3. For animals #2 and #4 cornea score was 1 at the 24 h reading but effects vanished thereafter. There were no iridial effects in all animals. At the 24, 48 and 72 h reading all animals showed some conjunctival redness (score 1), but this effect persistet only in animal #2 until the 7 days reading. No conjunctival redness was observed in animal #2 at the 14 days reading. Chemosis score was 0 throughout the experiment for animal #1. Animals #2, #3, and #4 showed some swelling (score 1) at the 24 hour reading but did not show any effects at the 48 h reading. Slight discharge was seen in 3 out of 4 animals at the 24 h reading, but not thereafter.

Read-across justification: for details please see read-across report in IUCLID section 13

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study N-Butyl Acetate was not irritating to the eyes.

Executive summary:

New Zealand white rabbits were exposed to 0.1 mL of undiluted n-Butyl acetate and were observed for up to 14 days where necessary. Overall no iritis occurred and only barely perceptible effects were seen on the cornea (score:1) as well as the conjunctivae (redness score:1, chemosis score: 1), which were all reversible within a maximum of 14 days (ECETOC, 1998).

This study was judged to be reliable with restrictions (RL2) and therefore selected as key study (read-across from supporting substance).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

For isobutyl acetate, no valid studies concerning skin or eye irritation / corrosion or on respiratory irritation could be identified. There are only publications of low reliability (RL3 or 4) available.

 To assess the skin, eye irritation / corrosion and respitatory irritation potential of isobutyl acetate, data for n-butyl acetate as supporting substance (structural analogue) will be used based on following reasons.

 Isobutyl acetate is closely related to n-butyl acetate. Both compounds are only different in the terminal methyl group position of the butyl alcohol part of the molecule. Physical and chemical properties are only slightly influenced by this difference. Physical and chemical reactivity will basically be the same and only differ gradually. On this basis, local effects exerted from both substances are expected to be quite similar. Thus, it is justified to use n-butyl acetate as supporting substance in the evaluation of irritation / corrosion effects of isobutyl acetate. Further details on read-across justification can be found in the read-across documentation in section 13. 

Skin irritation / corrosion

 To assess the skin irritation / corrosion potential of isobutyl acetate, data originated from n-butyl acetate as supporting substance will be used.

 DCC/BRRC 1987 (supporting substance n-butyl acetate)

 N-Butyl Acetate was evaluated for dermal irritation in rabbits in a reliable study (RL2) which was selected as key study. A 4-hour occlusive treatment similar to OECD TG 404 with 0.5 mL of test item did not induce any erythema or edema. Therefore, the test item does not reveal any irritating potential under the conditions tested (DCC/BRRC, 1987).

 Based on results from the supporting substance n-butyl acetate, isobutyl acetate can be assessed to be not irritating to the skin.

 

Eye irritation

 To assess the eye irritation potential of isobutyl acetate, data originated from n-butyl acetate as supporting substance will be used.

ECETOC, 1998 (supporting substance n-butyl acetate)

In this GLP conform study according to OECD TG 405 New Zealandwhite rabbits were exposed to 0.1 mL of undiluted n-Butyl acetate (99% purity) and were observed for up to 14 days where necessary. Overall no iritis occurred and only barely perceptible effects were seen on the cornea (score:1) as well as the conjunctivae (redness score:1, chemosis score: 1), which were all reversible within a maximum of 14 days (ECETOC, 1998).

This study was judged to be reliable with restrictions (RL2).

 

DCC/BRRC 1987 (supporting substance n-butyl acetate)

 Eye irritancy potential of n-butyl acetate was examined in a reliable study with rabbits (similar to OECD TG 405). No corneal injury in any of 6 eyes, iritis in 4 eyes at 1 and 4 hours after instillation, minor to moderate conjunctival irritation (redness and chemosis) in 6 eyes resulted from 0.1 mL of test substance (all healed at 48 hr). Mean scores (24, 48, and 72 h readings) over all 6 rabbit eyes were: cornea score = 0, iris score = 0.06, conjunctivae score = 0.33 and chemosis score = 0.06 (DCC/BRRC 1987).

 Based on results from the supporting substance n-butyl acetate, isobutyl acetate can be assessed to be not irritating to the eye.

Respiratory irritation

To assess the respiratory irritation potential of isobutyl acetate, data originated from n-butyl acetate as supporting substance (structural analogue) will be used.

Iregren 1993 (supporting substance n-butyl acetate, cf. study record in section 7.10.3)

 

Iregren et al. (1993) tested the irritating potential of n-butyl acetate in nonsmoking volunteers in a series of three different chamber studies. The irritative effects were evaluated on the basis of the subjective feeling of irritation, clinical examination of eye irritation and the lung function. The first group of volunteers (Experiment I) was exposed to concentrations of 350, 700, 1050 and 1400 mg/m³ (72.5, 145, 220 and 290 ppm). Exposure lasted 20 minutes and was repeated four times in intervals of 24 h. Under these conditions, subjects reported irritation to the throat, difficulties in breathing and a sensation of a bad smell. There were trends towards increasing effects with increasing exposure level, although the observed effects were only weak and no significant differences in effect size between any of the exposure concentrations and the baseline level before exposure were observed.

In the second test (Experiment II), volunteers were exposed to 70 (“control” level) and 1400 mg/m³ n-butyl acetate (14.5 and 290 ppm) two times for 20 min at intervals of 7 h. In this test, ratings for irritation of all sites except skin, differed significantly between 290 ppm and the control, although the irritation was not felt to be severe. Accustoming to the bad smell occurred depending on exposure time and exposure level.

In the third part of the study, subjects were exposed to 70 and 700 mg/m³ n-butyl acetate (14.5 and 145 ppm) twice for 4 h within seven days. Significant differences in the extent of throat irritation, difficulties in breathing and sensation of a bad smell were reported, but no differences in ocular irritation were determined. Altogether, the authors of the study concluded a rather low irritating potential of n-butyl acetate.

The study is reliable with restrictions (RL2).

Nelson 1943 (supporting substance n-butyl acetate,cf. study record in section 7.10.3)

Ten volunteers were exposed to n-butyl acetate for 3 -5 minutes. The test persons themselves subjectively scored the extent of irritation (no reaction, slightly irritating, very irritating): The majority of the test persons reported irritation of the throat at 200 ppm (964 mg/m3) while irritation of the eyes and nose was reported by the majority of the test persons at 300 ppm (1446 mg/m3), which resulted in severe irritation of the throat.

In summary, the investigations with human volunteers indicate, that weak irritation of the eyes and respiratory tract occurs after short term inhalation exposure to concentrations of about 200 ppm. In one study throat irritation was already reported after 4 h exposure to 145 ppm.

Justification for selection of skin irritation / corrosion endpoint:
Adequate read-across study available of high reliability (Klimisch score 2)

Justification for selection of eye irritation endpoint:
Adequate read-across study of high reliability (Klimisch score 2, according to guideline and GLP)

Justification for classification or non-classification

For isobutyl acetate, no valid data on irritation / corrosion could be located.

To compensate for this lack of data, information resulting from n-butyl acetate as supporting substance are used as substitute (read-across from supporting substance (structural analogue or surrogate).

 

According to the negative findings in the key studies described above isobutyl acetate has not to be classified for irritation of the skin nor for irritation of the eyes according to the criteria set in the Regulation (EC) No. 1272/2008.

According to the results obtained for n-butyl acetate and described by Iregren (1993) it is concluded that there is no need to classify Isobutyl Acetate for respiratory irritation.

Due to the defatting solvent character of Isobutyl acetate it is assumed that frequent contact can lead to skin dryness of cracking of the skin. Therefore, it is proposed to classify Isobutyl acetate with EUH066 (Repeated exposure may cause skin dryness or cracking).