Isobutyl acetate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-02-02 - 1988-02-26

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without GLP and with minor deviations

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted 1981

Deviations:

yes

Remarks:

: Reliability check (positive control) is not given , control group consisted only of 9 animals

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

GPMT study on substance was available and technical standard at the time when it was performed. As the result are sufficiently reliable no further in vivo testing is adequate.

Species:

guinea pig

Strain:

other: Bor:DHPW albino

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 330,7 g
- Housing: 1 to 5 animals in Macrolon cages Typ IV
- Diet (e.g. ad libitum): G4 Allein diet for giunea pigs, Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 - 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

maize oil

Concentration / amount:

Intradermal induction:
- FCA / water (1:1)
- 10% test substance in maize oil
- 10% test substance in maize oil and FCA (1:1)

epicutaneous induction (48 h):
- 100% test substance

challenge (24 h):
- 100% test substance

Route:

epicutaneous, occlusive

Vehicle:

maize oil

Concentration / amount:

Intradermal induction:
- FCA / water (1:1)
- 10% test substance in maize oil
- 10% test substance in maize oil and FCA (1:1)

epicutaneous induction (48 h):
- 100% test substance

challenge (24 h):
- 100% test substance

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection and topical application)
- Exposure period: topical application: 48 hr
- Test groups: Injection: TS in maize oil/FCA 1:1, topical application: TS loaded filter paper
- Control group: Injection: maize oil/FCA 1:1, topical application: patch loaded with maize oil
- Site: shoulder region
- Frequency of applications: topical application 7 days after intradermal injection
- Concentrations: 10% TS in maize oil and pure TS respectively

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hr
- Test groups: pure TS on filter paper
- Control group: pure TS on filter paper
- Site: flank
- Evaluation (hr after challenge): 24 and 48 hr after end of exposure time

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% test substance

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% test substance

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% test substance

No. with + reactions:

0

Total no. in group:

9

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 9.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% test substance

No. with + reactions:

0

Total no. in group:

9

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100% test substance. No with. + reactions: 0.0. Total no. in groups: 9.0.

Group:

positive control

Remarks on result:

not measured/tested

No skin reactions were observed in any of the 20 test animals neither at 48 hours nor at 72 hours after the start of the challenge application.

There was no adverse effect on the development of the body weight of the test and control animals.

Body weight development (mean of all animals in g)

	Test begin	Test end	Weight gain (three weeks)
Test group	330.7	446.1	115.4
Controls	335.0	472.4	137.4

During the test the following local reactions were observed:

Induction treatment - after intradermal injection

test animals		controls
FCA / Water (1:1)	pronounced erythema and swelling as well as necrosis at the injection site	FCA / Water (1:1)	pronounced erythema and swelling as well as necrosis at the injection site
10% TS in maize oil	pronounced erythema and swelling at the injection site	maize oil	slight erythema and swelling at the injection site
10% TS in FCA / maize oil (1:1)	pronounced erythema and swelling as well as slight necrosis at the injection site	FCA / maize oil (1.1)	pronounced erythema and swelling as well as slight necrosis at the injection site

Induction treatment - after topical application

Inflammation of all injection sites treated with FCA.

24 hours after patch removel scab formation at the injection site.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Isobutyl acetate did not meet the criteria for a skin sensitizer according to Directive 2001/59/EC in a Guinea pig maximization test performed according to OECD TG 406

Executive summary:

In a dermal sensitization study isobutyl acetate (purity ca 98%) was tested using a Guinea Pig Maximisation Test according to OECD test guideline 406 (Skin Sensitization), adopted 1981. 20 test animals were induced by intradermal injection of 0.1 mL of 10% TS in maize oil and and 0.1 mL of 10% TS in a 1:1 mixture of FCA and maize oil. For the topical application the injection site was treated 7days after the initial injection for 48 hours with pure TS (patch application). Challenge exposure followed after 14 days. Pure TS loaded on a patch was applied for 24 hours to one flank of the test animals. Reading of the skin reaction of test and control animals was taken 48 and 72 hours after the start of the challenge application.

For induction, controls (9 animals) were treated such as the test animals but with test mixtures without TS for induction. None of the animals showed skin reactions at the performed readings after challenge with 100% test substance.

No skin reactions in any of the 20 test animals were observed either at 48 hours or at 72 hours after the start of the challenge application. There was no adverse effect on the development of the body weight of the test and control animals. In this study, isobutylacetate is not a dermal sensitizer.

This study is classified as reliable with restrictions due to minor deviatons from the OECD test guideline 406 (no reliability check (positive control), only 9 controls). In addition, it is not a GLP study. Yet the study results are considered to be valid since the deviations are only of little importance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

For assessment of the skin sensitization potential of isobutyl acetate, only one valid study is available (Huels AG, 1988). The publication of Opdyke/Epstein (1978) is a review article reporting toxic effects of isobutyl acetate in summary (secondary source).

 

Huels AG (1988)

In a valid dermal sensitization study isobutyl acetate (purity ca 98%) was tested using a Guinea Pig Maximisation Test according to OECD test guideline 406 (Skin Sensitization), adopted 1981.

 

No skin reactions in any of the 20 test animals were observed either at 48 hours or at 72 hours after the start of the challenge application. There was no adverse effect on the development of the body weight of the test and control animals. In this study, isobutyl acetate is not a dermal sensitizer.

In the study cited from secondary source (Opdyke/Epstein, 1978, RL4) 28 human volunteers were treated according to the scheme of maximization test by Kligman (Kligman and Epstein 1975). Using a 2% isobutyl acetate solution in petrolatum, no skin sensitization reaction was produced, further supporting the fact that isobutyl acetate is not a dermal senistizer.

Migrated from Short description of key information:
In a Guinea Pig Maximization Test according to OECD TG 406, isobutyl acetate did not cause any skin reactions in the test animals.

Justification for selection of skin sensitisation endpoint:
Only one adequate study available of high reliability (Klimisch score 2)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
There are no data on sensitization by inhalation.

Justification for classification or non-classification

Isobutyl acetate was not a skin sensitiser in a guinea pig maximisation test. Therefore, Isobutyl acetate has not to be classified according to Regulation (EC) No 1272/2008.

There are no data on sensitization by inhalation.