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Administrative data

Description of key information

n-butyl acetate is not irritating to the skin and not irritating to the eyes. There is no need to classify n-Butyl Acetate for respiratory irritation. 

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.
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:
other: 24, 48 and 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:
other: 24, 48 and 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.

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 test item 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 (Myers et al., 1987).

This study was judged to be reliable (RL2) and therefore was selected as key study.

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
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:
other: 24-28-72 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:
other: 24-48-72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 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:
other: 24-48-72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 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:
other: 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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

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 with the test item similar to OECD TG 404 did not induce any erythema nor edema. Therefore the test item is not irritating to skin under the conditions tested (Myers et al., 1987, corrsponds to IUCLID study record DCC/Bushy Run research Center). These findings are supported by two studies of lower reliability.

A very weak irritation (at least visible capillary injection) was observed in rabbits when the animals were exposed for 24 hours to 0.01 ml of the test substance on the clipped skin (Smyth et al., 1954, RL3). If 1 mL of n-butyl acetate was applied under occlusive conditions for different times onto the clipped skin of 20 albino guinea pigs no pathological changes could be observed in the examined skin (Kronevi et al., 1979, RL3). All these findings support the conclusion that n-butyl acetate is not irritating to skin.

Eye irritation

Eye irritancy potential of n-butyl acetate was examined in a reliable study with rabbits (accoring to OECD TG 405 and GLP conform) which was selected as key study. White rabbits were exposed to 0.1 mL of undiluted n-butyl acetate (99% purity) and were observed for up to 14 days where necessary. 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; RL2).

Another study supported the finding that n-butyl acetate is not irritating to the eyes of rabbits. 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 effects were reversible after 48 hr). Further investigations were made after the instillation of 0.005 mL of test substance, no corneal injury in any of 6 eyes, iritis in 2 at 1 and 4 hours post application, minor to moderate conjunctival irritation in 6 eyes (1, 4 and 24 hours after instillation) were found under these test conditions (fully reversible after 48 hr;Myers et al., 1987, corresponds to IUCLID study record DCC/Bushy Run Research Center).

Kennah et al. (1989)reported that n-butyl acetate is a mild eye irritant. However, the authors measured the corneal thickness and did not use the Draize score. Therefore, the study was judged not to be reliable (RL3). n-Butyl acetate (0.005 mL) caused severe burns after instillation to the eyes. However, this study is reported insufficiently and was therefore judged not to be reliable (RL3; Smyth et al., 1954). One case of a chemical burn of the cornea of a worker was reported, which could be healed within 48 hours (McLaughlin, 1946; RL3; no further information). Based on the results of the reliable studies it is concluded that n-butyl acetate is not irritating to eyes according to the criteria of the Regulation (EC) No 1272/2008.

Exposure to n-butyl acetate for 5 minutes (2 -4 volunteers) resulted in weak (1 mg/L; about 210 ppm) or moderate (10 mg/L; about 2100 ppm) irritation of the eyes, nose, throat and trachea (Flury and Wirth, 1933).

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 (Nelson et al., 1943).

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.

In two animal studies which did not follow any guidelines (RL3) slightly irritating effects on the eyes were observed after inhalation exposure: Guinea pigs which were exposed to 3300 ppm n-butyl acetate vapour showed squinting as well as lacrimation immediately after the start of the exposure (Sayers et al., 1936). Cats which were repeatedly exposed to n-butyl acetate in the gas phase (≥ 14.5 mg/L, about 3000 ppm) revealed irritation of the eyes (lacrimation, closed lids), but this effects diminished with ongoing exposure (Flury and Wirth, 1933).

Respiratory irritation

In studies investigating acute and repeated inhalation toxicity irritation of the respiratory tract was observed. In acute toxicity studies clinical signs like bloody noses, red discharge and reddish crusts around the nose were observed immediately after end of the exposure. These effects were partially reversible, since no histopathologic findings were observed at the end of the post observation period. Additionally, severe effects like lung atelectasis, hyperaemic lungs, vesicular emphysema and fluid in the thoracic cavity and in the trachea were observed.

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).


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

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

Justification for classification or non-classification

According to the negative findings in the most reliable key studies n-butyl 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 Iregren (1993) it is concluded that there is no need to classify n-Butyl Acetate for respiratory irritation.

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