tert-pentyl 2-ethylperoxyhexanoate

Endpoint summary

Description of key information

According to EU Regulation (EC) N° 1272/2008 (CLP), the substance should be classified as a skin sensitizer, category 1B, as 50 % positive response were obtained with an intradermic induction dose of 1 % in the GPMT.

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:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: 1A: GLP, OECD N°406 Guideline (1992, July 17th)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

date of study is before official adoption of LLNA guideline

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Species and strain: Dunkin-Hartley guinea-pigs.
- Reason for this choice: species generally accepted by regulatory authorities for this type of study. The strain used has been shown to produce a satisfactory sensitization response using known sensitizers.
- Breeder: Charles River France, 76410 Saint-Aubin-lès-Elbeuf, France.
- two males and two females for the preliminary test,
- Females were nulliparous and non-pregnant.
-Weight: on day 1, the animals of the main test were approximately 3 months old and bad a mean body weight ± standard deviation of 369 ± 24 g for the males and 362 ± 18 g for the females.
- Acclimatization: at least 5 days before the beginning of the study.
- Identification of the animals: ear-tattoo.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2°C
- Humidity (%): 30-70 %
- Air changes (per hr): approx. 12
- Photoperiod (hrs dark / hrs light): 12/12

No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

intradermal induction: 5%
cutaneous induction: undiluted
cutaneous challenge: undiluted

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

intradermal induction: 5%
cutaneous induction: undiluted
cutaneous challenge: undiluted

No. of animals per dose:

Control group: 5 males and 5 females
Treated group: 10 males and 10 females

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
* Intradermal induction:
- On day 1, 3injections are realized on the scapular area:
- 0.1mL of Freund's complete adjuvant at 50% in 0.9% NaCl
- 0.1mL of the test item at 5 % (for treated group) or 0.1mL of vehicle (for control group)
- 0.1mL of a mixture 50/50 (V/V) of Freund's complete adjuvant in 0.9% NaCl and the test item at 5 % (for treated group) or the vehicle (for control group).

* Cutaneous induction:
- On day 7, local irritation is induced by application of Sodium Laurylsulfate 10% in Vaseline
- On day 8, occlusive application on the scapular area of 0.5mL of the test item 10% (for treated group) or vehicle (for control group) for 48 hours

B. CHALLENGE EXPOSURE D22
On day 22, 24hours occlusive application on the scapular area of 0.5mL of the undiluted test item on the right flank and 0.5mL of the vehicle on the left flank.
Reactions are evaluated 24 and 48 hours after removal of the dressing

Challenge controls:

No

Positive control substance(s):

yes

Remarks:

Date-Study n°CIT/Study No. 17335 TSG; dinitrochlorobenzene

Positive control results:

Dinitro 2,4 Chlorobenzene : Positive result in recent study on ( ) females. Induction: test substance injected intradermally 0.05% (d1) and applied cutaneously 0.5% (d8). Challenge (d22): 0,1% r flank 0.5% l flank

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

9

Total no. in group:

20

Clinical observations:

score of more than 2 were considered positive

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 9.0. Total no. in groups: 20.0. Clinical observations: score of more than 2 were considered positive.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0.

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

only dryness of the skin was observed

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: only dryness of the skin was observed.

Individual scoring:

Group	Sex	Animal	24h				48h
			Erythema		Oedema		Erythema		Oedema
			LF	RF	LF	RF	LF	RF	LF	RF
Control	M	31	0	0	0	0	0	0	0	0
		32	0	0	0	0	0	0	0	0
		33	0	0	0	0	0	0	0	0
		34	0	0	0	0	0	0	0	0
		35	0	0	0	0	0	0	0	0
Control	F	46	0	0	0	0	0	0	0	0
		47	0	0	0	0	0	0	0	0
		48	0	0	0	0	0	0	0	0
		49	0	0	0	0	0	0	0	0
		50	0	0	0	0	0	0	0	0
Treated	M	36	0	0	0	0	0	0	0	0
		37	0	1	0	0	0	0/S	0	0
		38	0	0	0	0	0	0	0	0
		39	0	0	0	0	0	0	0	0
		40	0	1	0	0	0	0/S	0	0
		41	0	2	0	0	0	0/S	0	0
		42	0	1	0	0	0	0	0	0
		43	0	2	0	0	0	0/S	0	0
		44	0	2	0	0	0	0/S	0	0
		45	0	1	0	0	0	0/S	0	0
Treated	F	51	0	1	0	0	0	0	0	0
		52	0	2	0	0	0	0/S	0	0
		53	0	2	0	0	0	0/S	0	0
		54	0	2	0	0	0	0/S	0	0
		55	0	2	0	0	0	0	0	0
		56	0	1	0	0	0	0	0	0
		57	0	1	0	0	0	0	0	0
		58	0	2	0	0	0	0/S	0	0
		59	0	1	0	0	0	0/S	0	0
		60	0	2	0	0	0	0/S	0	0

 

LF=left flank

RF=right flank

A=crusts

S=dryness of the skin

No cutaneous reactions were observed in the animals of the control group.

In the treated group, at the 24-hour reading, a very slight (grade 1) or well-defined (grade 2)

erythema was noted in 8/20 and 9/20 animals, respectively.

 

No erythema persisted at the 48-hour reading. Dryness of  the skin was observed in

12/20 animals.

 

The observed erythema with a score higher than 1 were considered as delayed contact hypersensitivity reactions.

no visible change.............................................................................................0

discrete or patchy erythema.............................................................................1

moderate and confluent erythema.....................................................................2

intense erythema..............................................................................................3

Interpretation of results:

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

Conclusions:

Under these experimental conditions and according to the maximization method of Magnusson and Kligman, the test substance t-amy peroxyethyl-2-hexanoate induces delayed contact hypersensitivity in 9/20 (45%) guinea-pigs, with an intradermal induction dose of 5 % and undiluted substance for cutaneous application.

Executive summary:

The delayed contact hypersensivity of t-amy peroxyethyl-2-hexanoate was evaluated in Guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) and in compliance with GLP.

The induction phase has been realized both by intradermal route on day 1 (5in vehicle) and by cutaneous route on day 8 (undiluted) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 22 by cutaneous application of the undiluted substance on the right flank (vehicle on the left flank); the cutaneous reactions were scored 24 and 48 hours after the challenge phase.

No cutaneous reactions were observed in the animals of the control group. In the treated group, at the 24-hour reading, a very slight (grade 1) or well-defined (grade 2) erythema was noted in 8/20 and 9/20 animals, respectively. No erythema persisted at the 48-hour reading. Dryness of  the skin was observed in12/20 animals. The observed erythema with a score higher than 1 were considered as delayed contact hypersensitivity reactions.

In conclusion, the test item was considered as sensitizing in guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

For this endpoint, a Klimisch 1study is available (Manciaux, 1999): the delayed contact hypersensivity of tert-amyl peroxyethyl-2-hexanoate was evaluated in guinea pigs according to OECD N°406 guideline (Magnusson and Kligman test) and in compliance with GLP. The induction phase has been realized both by intradermal route on day 1 (5% in vehicle) and by cutaneous route on day 8 (undiluted) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 22 by cutaneous application of the undiluted substance on the right flank (vehicle on the left flank); the cutaneous reactions were scored 24 and 48 hours after the challenge phase. No cutaneous reactions were observed in the animals of the control group. In the treated group, at the 24-hour reading, a very slight (grade 1) or well-defined (grade 2) erythema was noted in 8/20 and 9/20 animals, respectively. No erythema persisted at the 48-hour reading. Dryness of  the skin was observed in12/20 animals. The observed erythema with a score higher than 1 were considered as delayed contact hypersensitivity reactions.

In conclusion, the test item was considered as sensitizing in guinea pigs.

Migrated from Short description of key information:
Tert-amyl peroxyethyl-2-hexanoate induced skin sensitisation in a GPMT study (Manciaux, 1999). It is considered as a moderate skin sensitizer.

Justification for selection of skin sensitisation endpoint:
Key study, Klimisch 1.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

There is no data regarding the sensitisation potential by inhalation route.

Justification for classification or non-classification

According to EU Regulation (EC) N° 1272/2008 (CLP), the substance should be classified as a skin sensitizer, category 1B, as 50 % positive response were obtained with an intradermic induction dose of 1 % in the GPMT.