tert-butyl peracetate

Endpoint summary

Description of key information

The test substance (50% in aromatic free mineral spirit) was assessed for skin sensitization in a Guinea pig maximization test according to EU method B.6 and OECD guideline 406. Based on the results obtained the test substance was considered to cause skin sensitisation.

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:

1998-10-19 and 1998-11-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The Guinea Pig Test (1999) met the previous requirements before the entry into force of REACH. The test is suitable and reliable to cover this endpoint. For this reason and for animal welfare reasons, no further in vivo study (LLNA test) needs to be performed.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: approx. 4 weeks
- Weight at study initiation: individual bw did not exceed 500 g
- Housing: 5 animals per labelled metal cage with wire-mesh floors
- Diet: standard guinea pig diet, including ascorbic acid (1600 mg/kg), LC-23 B, pellet diameter 4 mm (Hope farms, Woerden, The Netherlands), ad libitum; hay once a week
- Water: tap-water, diluted with decalcified water; ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

intradermal injection:
a) 10%
b) 1:1 mixture of FCA and 20% test substance concentration
epidermal application:
50% test substance concentration

Route:

epicutaneous, semiocclusive

Vehicle:

corn oil

Concentration / amount:

epidermal, challenge:
10% test substance concentration

No. of animals per dose:

experimental group: 10 females
control group: 5 females

Details on study design:

RANGE FINDING TESTS:
A. INTRADERMAL INJECTIONS:
- Concentrations: 100%, 50%, 20% and 10% test substance
- each of two animals received two different concentrations in duplicate (0.1 mL/site) in the clipped scapular region
- the injection sites were assessed for irritation 24 and 48 hours after treatment

B. EPIDERMAL APPLICATION:
- Concentrations: 100%, 50%, 20% and 10% test substance
- 2 different concentrations were applied (0.5 mL each) per animal to the clipped flank
- animals receiving intradermal injections were treated with the lowest concentrations and two further animals with the highest concentrations
- Time of exposure: 24 hours
- Observation point after exposure: 24 and 48 hours

MAIN STUDY
A.1. INDUCTION EXPOSURE (intradermal), on day 1
- Exposure period: three pairs of intradermal injections (0.1 mL/site)
- Test groups: (A) 1:1 mixture (w/w) of FCA and water, (B) 10% test substance concentration, (C) 1:1 mixture (w/w) of FCA and a 20% test substance concentration
- Control group: were treated as decribed for the experimental animals, except that, instead of the test substance, the vehicle was administered
- Site: scalpular region; one of each pair was on each side of the midline and from cranial (A) to caudal (C)
- Duration: single injection

A.2 INDUCTION EXPOSURE (epidermal), on day 8
- Test group: 50% test substance concentration
- Control group: see comment in section A.1.
- Site: scalpular area between the injection sites
- Duration 48 hours

B. CHALLENGE EXPOSURE; on day 22
- No. of exposures: 1
- Exposure period: 24 hours
- Test group and control group: 10% test substance concentration and the vehicle
- Site: flank
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

Alpha-Hexylcinnamicaldehyde, Tech. 85%

Positive control results:

The results lead to a sensitisation rate of 100 per cent of the 10% concentration. From these results, it was concluded that the female guinea pig of the albino Dunkin Hartley strain is an appropriate animal model for the performance of studies designed to evaluate the sensitising potential of a substance in a Maximisation type of test.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

5

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

5

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

5

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

7

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

one animal showed scaliness

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

not measured/tested

No mortality occured and no symptoms of systemic toxicity were observed in the animals of the main study.

Body weights and body weight gain of the experimental animals remained in the same range as controls over the study period.

Seven animals of the 24 readings and seven animals of the 48 readings in the challenge phase were considered indicative of sensitisation. In sum eight different animals were considered indicative of sensitisation.

 

The skin effects caused by the intradermal injections and epidermal exposure during the induction phase are given in the following table.

Animal Number	Intradermal Injection (Day 3) A                                            B                                                    C			Epidermal Exposure (Day 10)                          D
Control 1 2 3 4 5	E2 E3 E3 E3 E4	E2 E1 NA NA NA	E3 E3 E2 E3 E3	Erythema 0 0 0 0 0	Oedema 0 0 0 0 0
Experimental 6 7 8 9 10 11 12 13 14 15	E2 E3 E2 E2 E3 E3 E3 E3 E2 E2	E1 E3 NA E1 E2 E1 E1 E1 E1 E1	E2 E3 E3 E4 E4 E4 E3 E3 E3 E2	2 2 0 2 2 2 2 3 1 2	0 0 0 0 0 0 0 0 0 0

A. 1:1 Mix of FCA and water

B. 10% test substance concentration (experimental); vehicle (control)

C. 1:1 Mix of FCA and a 20% concentration (experimental) or vehicle (control)

D. 50% test substance concentration (experimental); vehicle (control)

Skin effects intradermal injections: NA no abnormalities; E( ) Erythema (grade)

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

The skin reactions observed in response to a 10% test substance concentration in 7 (of the 10) experimental animals in the challenge phase were considered indicative of sensitisation, based on the absence of any response in the control animals. The results indicate a sensitisation rate of 70 per cent.

Executive summary:

The test substance (50% in aromatic free mineral spirit) were tested for contact hypersensitivity in the albino guinea pig according to the EU method B6, the OECD guideline 406 and based on the method described by Magnusson and Kligman. Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, 10 experimental animals were intradermally injected with 10% concentration and epidermally exposed to a 50% concentration. 5 control animals were similarly treated, but with the vehicle (corn oil) only. Two weeks after the epidermal application all animals were challenged with a 10% test substance concentration and the vehicle.

No mortality occured and no symptoms of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Skin reactions of grade 1 were observed in eight experimental animals in response to the 10% test substance concentration. No skin reactions were evident in the control animals. Scaliness was seen in the treated skin site of one experimental animal. The skin reactions observed in response to a 10% test substance concentration in 7 (of the 10) experimental animals in the challenge phase were considered indicative of sensitisation, based on the absence of any response in the control animals. The results indicate a sensitisation rate of 70 per cent.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitisation

The test substance was tested for contact hypersensitivity in the albino guinea pig according to the EU method B6, the OECD guideline 406 and based on the method described by Magnusson and Kligman. Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, 10 experimental animals were intradermally injected with 10% concentration and epidermally exposed to a 50% concentration. 5 control animals were similarly treated, but with the vehicle (corn oil) only. Two weeks after the epidermal application all animals were challenged with a 10% test substance concentration and the vehicle.

No mortality occured and no symptoms of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Skin reactions of grade 1 were observed in eight experimental animals in response to the 10% test substance concentration. No skin reactions were evident in the control animals. Scaliness was seen in the treated skin site of one experimental animal. The skin reactions observed in response to a 10% test substance concentration in 7 (of the 10) experimental animals in the challenge phase were considered indicative of sensitisation, based on the absence of any response in the control animals. The results indicate a sensitisation rate of 70 per cent.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

Based on available data, the test item is classified and labelled as Skin Sensitiser Category 1B (H317: "may cause an allergic skin reaction) according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.