Ethyl 3,5,5-trimethylhexanoate

Endpoint summary

Description of key information

for In vivo skin sensitisation, two studies are available, considered in a Weight of Evidence approach:

1) GPMT (OECD 406, not GLP, Klimisch Rel.2): Not sensitizing

2) GPMT (OECD 406, GLP, Klimisch Rel.2): Not sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

from 6th of June to 1st of July fo 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

no data if induction produced irritation reaction + no pretreatment

GLP compliance:

no

Remarks:

study performed before implementation of GLP at OECD level

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

test conducted before first publication of OECD 429 (LLNA test)

Species:

guinea pig

Strain:

other: Pirbright white

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen
- Weight at study initiation: 396 g (mean, test group), 400 g (mean, control group)
- Housing: in groups of 5 in Makrolon cages, type 4
- Diet (e.g. ad libitum): guinea pig diet Altromin 3022, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 21
- Humidity (%): approx. 50
- Air changes (per hr): 11
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

other: propylen glycol (intradermal / challenge), vaseline (epicutaneous)

Concentration / amount:

intradermal induction: 5% in propylene glycol,
epicutaneous induction: 5% in vaseline,
challenge: 1% in propylen glycol

Route:

epicutaneous, occlusive

Vehicle:

other: propylen glycol (intradermal / challenge), vaseline (epicutaneous)

Concentration / amount:

intradermal induction: 5% in propylene glycol,
epicutaneous induction: 5% in vaseline,
challenge: 1% in propylen glycol

No. of animals per dose:

20 (test group), 20 (control)

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 dermal
- Exposure period: 48 h (dermal)
- Test groups: 5% test substance
- Control group: propylene glycol (intradermal) / vaseline (epicutaneous)
- Site: above the shoulder blades
- Concentrations:
Intradermal:
0.1 mL FCA (mixed at a ratio of 1+1 in vehicle)
0.1 mL 5% test substance in propylene glycol
0.1 mL 5% test substance + FCA (mixed at a ratio of 1+1 in propylene glycol)
Epicutaneous:
5% in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: day 22 (14 d after epicutaneous induction)
- Exposure period: 24 h
- Test groups: right flank: propylene glycol, left flank: test substance 1% in propylene glycol
- Control group: right flank: propylene glycol, left flank: test substance 1% in propylene glycol
- Evaluation (hr after challenge): 24, 48

OTHER: no pretreatment with irritating substance / no information whether substance at applied concentration was minimally irritating as stipulated in the guideline

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

19

Clinical observations:

one animal found dead 24 h after challenge

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: one animal found dead 24 h after challenge.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

19

Clinical observations:

one animal found dead 24 h after challenge

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: one animal found dead 24 h after challenge.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

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

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Interpretation of results:

GHS criteria not met

Conclusions:

3,5,5-Trimethyl-ethyl capronate was not sensitising in this study.

Executive summary:

In a dermal sensitisation study similar to OECD guideline 406 with 3,5,5-Trimethyl-ethyl capronate, 20 female Pirbright white guinea pigswere tested using the method of method of Magnusson & Kligman (Guinea Pig Maximisation Test).

Intradermal induction was performed with 5% in propylene glycol, epicutaneous induction with 5% in vaseline, challenge with 1% in propylen glycol. The animals were not pretreated to generate local irritation before epicutaneous induction.

After challenge no visible changes of the treated skin sites were observed in the test and control group animals 24 and 48 h after patch removal (= grade 0).

The test material produced a response in 0% of animals. According to CLP, EU GHS (Regulation (EC) No 1272/2008), a response of at least 30% of the test animals of an adjuvant type guinea pig test method for skin sensitisation is considered as positive.

Therefore 3,5,5-Trimethyl-ethyl capronate is not a dermal sensitiser in this study.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

from 18th of August to 8th of October 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

Principles of method if other than guideline:

non-adjuvant-method: Klecak, G., Geleick, H. & Frey, J.R., J. Soc. Cosmet. Chem. 28, 53-64 (1977)

GLP compliance:

yes (incl. QA statement)

Type of study:

open epicutaneous test

Justification for non-LLNA method:

test conducted before first publication of OECD 429 (LLNA test)

Species:

guinea pig

Strain:

other: Pirbright white, Bor : DHPW

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, D-Borchen
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: approx. 330 g
- Housing: in groups of 3 animals in Makrolon Type IV cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted Altromin Maintenance Diet 3022, Batch no. 100692/1428 and 030792/0828, ad libitum; carrots regularly added
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, open

Vehicle:

other: ethanol

Concentration / amount:

preliminary study: 0, 3, 10, 30, 100%
main study: induction: 10, 30% / challenge: 10, 30%

Route:

epicutaneous, open

Vehicle:

other: ethanol

Concentration / amount:

preliminary study: 0, 3, 10, 30, 100%
main study: induction: 10, 30% / challenge: 10, 30%

No. of animals per dose:

3 (preliminary test), 6 (main study)

Details on study design:

RANGE FINDING TESTS:
Determination of the minimal irritating and maximal non-irritating concentrations of the test substance suitable for induction of sensitization and for sensitization challenge
The concentrations in a dose of 25 µL were tested as follows: left flank 0, 3, 10, 30, 100%

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 19
- Test groups:
Group 1: minimal irritating concentration (30% test substance), 100 µL
Group 2: maximal non-irritating concentration (10% test substance), 100 µL
- Control group: vehicle (70% ethanol from application 1-5, from 6th exposure: 50% ethanol)
- Site: left cranial flank
- Frequency of applications: 5 times/week
- Duration: unlimited

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 1st challenge: parallel to 16th induction exposure / 2nd challenge: 14 d after 1st
- Exposure period: unlimited
- Test groups: test substance
- Control group: test substance
- Site: right flanks (caudal 10%; cranial: 30%), 25 µL
- Concentrations: 10, 30%
- Evaluation (hr after challenge): 24, 48, 72

OTHER:
The 1st three applications were done mistakenly by 3% at treatment group 1 and 1% at treatment group 2. In the following applications the concentrations mentioned above were used.

Positive control substance(s):

yes

Remarks:

reliability checks were performed, but no further details given in the study report

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction 30%, challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction 30%, challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction 30%, challenge 30%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction 30%, challenge 30%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction 10%, challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction 10%, challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction 10%, challenge 30%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction 10%, challenge 30%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

challenge 30%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenge 30%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction 30%, challenge 10%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction 30%, challenge 10%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction 30%, challenge 30%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction 30%, challenge 30%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction 10%, challenge 10%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction 10%, challenge 10%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction 10%, challenge 30%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction 10%, challenge 30%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

challenge 30%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenge 30%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

induction 30%, challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: induction 30%, challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

induction 30%, challenge 30%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: induction 30%, challenge 30%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

induction 10%, challenge 10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: induction 10%, challenge 10%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

induction 10%, challenge 30%

No. with + reactions:

2

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: induction 10%, challenge 30%. No with. + reactions: 2.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

challenge 10%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenge 10%. No with. + reactions: 1.0. Total no. in groups: 6.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

challenge 30%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: challenge 30%. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

rechallenge

Group:

test chemical

Dose level:

all combinations and time points

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: rechallenge. Group: test group. Dose level: all combinations and time points. No with. + reactions: 0.0. Total no. in groups: 6.0.

Reading:

rechallenge

Group:

negative control

Dose level:

all concentrations and time points

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: Reading: rechallenge. Group: negative control. Dose level: all concentrations and time points. No with. + reactions: 0.0. Total no. in groups: 6.0.

Evaluation of dermal effects after challenge exposures

 

	1^stchallenge			2^ndchallenge
	24 h	48 h	72 h	24 h	48 h	72 h
	30% / 10%	30% / 10%	30% / 10%	30% / 10%	30% / 10%	30% / 10%
Control	0 / 0	1 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Control	---	---	---	0 / 0	0 / 0	0 / 0
	---	---	---	0 / 0	0 / 0	0 / 0
	---	---	---	0 / 0	0 / 0	0 / 0
	---	---	---	0 / 0	0 / 0	0 / 0
	---	---	---	0 / 0	0 / 0	0 / 0
	---	---	---	0 / 0	0 / 0	0 / 0
Test group, induction 30%	1 / 0	0 / 0	1 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Test group, induction 10%	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	1 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	1 / 1	1 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

 

Positive animals [%]	1^stchallenge			2^ndchallenge
	24 h	48 h	72 h	24 h	48 h	72 h
	30% / 10%	30% / 10%	30% / 10%	30% / 10%	30% / 10%	30% / 10%
Control 1	0 / 0	17 / 0	0 /17	0 / 0	0 / 0	0 / 0
Control 2	---	---	---	0 / 0	0 / 0	0 / 0
Test group, induction 30%	17 /0	17 / 17	17 / 0	0 / 0	0 / 0	0 / 0
Test group, induction 10%	0 / 0	17 / 17	33 / 0	0 / 0	0 / 0	0 / 0

 

No death occurred in the study. There was no significant difference in body weight gain between the treatment and the control groups.

Interpretation of results:

GHS criteria not met

Conclusions:

3,5,5-Trimethyl-ethyl capronate was not a dermal sensitiser in this study.

Executive summary:

In a dermal sensitisation study according to OECD guideline 406 (1981) with 3,5,5-Trimethyl-ethyl capronate, female Pirbright white guinea pigs (6/group) were tested using the Open epicutaneous test (Klecak, G., Geleick, H. & Frey, J.R., J. Soc. Cosmet. Chem. 28, 53-64 (1977)).

20 open epidermal inductions as well as challenge and rechallenge were performed with 10 and 30% test substance in ethanol. In a preliminary study the minimal irritating dose level was determined to be 30%, the maximum non irritating dose level was 10%.

During the induction period weak erythema or edema was observed in 2/6 animals from day 8 and in 1/6 animals in day 19 in the group treated with 10% test substance. Weak to moderateerythema and/or edema was observed during the induction period in all animals of thegroup treated with 30% test substance.

The first challenge with 30% test substance provoked weak dermal effects (grade 1) in up to 33% of the animals of the treatment groups and up to 17% of the animals of the control group. The first challenge with 10% test substance provoked weak dermal effects (grade 1) in up to 17% of the animals in both, treatment and control groups.

In the second challenge neither the 10% nor the 30% dilution of the test substance provoked any dermal effects.

According to Klecak (1977), a substance is considered allergenic when at least 25% of the animals showed positive reactions with non-irritant concentrations used for challenge.

Since no increased dermal alterations were observed in the animals of the treatment groups compared with the animals of the control groups after the first and second challenge, 3,5,5-Trimethyl-ethyl capronate is considered to be not sensitising in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Two studies are available for this substance.

1) In a dermal sensitisation study, 20 female Pirbright white guinea pigs were tested using the method of method of Magnusson & Kligman (Guinea Pig Maximisation Test). The test was conducted in GLP conditions.

Intradermal induction was performed with 5% test substance in propylene glycol, with and without adjuvant. Epicutaneous induction was performed with 5% in vaseline, and challenge with 1% in propylen glycol. The animals were not pretreated to generate local irritation before epicutaneous induction.

After challenge no visible changes of the treated skin sites were observed in the test and control group animals 24 and 48 h after patch removal (= grade 0).

The test material produced a response in 0% of animals. Therefore 3,5,5-Trimethyl-ethyl capronateis not a dermal sensitiser in this study.

2) In a dermal sensitisation study according to OECD guideline 406 , female Pirbright white guinea pigs (6/group) were tested with the registered substance using the Open epicutaneous test (Klecak, G., Geleick, H. & Frey, J.R., J. Soc. Cosmet. Chem. 28, 53-64 (1977)).

20 open epidermal inductions as well as challenge and rechallenge were performed with 10 and 30% test substance in ethanol. In a preliminary study the minimal irritating dose level was determined to be 30%, the maximum non irritating dose level was 10%.

During the induction period weak erythema or edema was observed in 2/6 animals from day 8 and in 1/6 animals in day 19 in the group treated with 10% test substance. Weak to moderateerythema and/or edema was observed during the induction period in all animals of thegroup treated with 30% test substance.

The first challenge with 30% test substance provoked weak dermal effects (grade 1) in up to 33% of the animals of the treatment groups and up to 17% of the animals of the control group. The first challenge with 10% test substance provoked weak dermal effects (grade 1) in up to 17% of the animals in both, treatment and control groups.

In the second challenge neither the 10% nor the 30% dilution of the test substance provoked any dermal effects.

According to Klecak (1977), asubstance is considered allergenic when at least 25% of the animals showed positive reactions with non-irritant concentrations used for challenge.

Since no increased dermal alterations were observed in the animals of the treatment groups compared with the animals of the control groups after the first and second challenge,3,5,5-Trimethyl-ethyl capronate is considered to be not sensitising in this study.

considering the two studies in a weight of evidence approach, the substance is considered to be not sensiter.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 and to the GHS.

Self-classification:

Based on the available data, the substance is not classified for Skin Sensitization.

No direct scientific data are available on the substance to address respiratory sensitisation.