Ethyl 3,5,5-trimethylhexanoate

Endpoint summary

Description of key information

Skin irritation:

In one study, conducted in 1994, under GLP conditions and following the OECD 404 Guideline, the test item (>90% purity) showed almost no irritant potential to the skin. This study is regarded as fully reliable, and a Klimisch 1 is assigned to it

In another study, conducted in 1992, under GLP conditions and following the OECD 404 Guideline, the test item showed an irritant potential because of an irreverisble effect to the skin after 21 days. This test was judged to be not fully reliable, and a Klimisch 2 is assigned to it. the main deviations found are:

- Test report contains less information than a standard Klimisch 1 test

- Sample origin is unclear. No batch number of purity is reported.

- Irritant scores follow a very strange pattern: On day 7, only a brownish discouloration is observed in the three experimental animals. On day 14, besides the discouloration, an scar is observed in one animal and a eschar in the other two. On day 21, however, a slight erythrema (grade 1) appears in 2 animals, that was not observed before.

Eye Irritation:

In one study, conducted in 1995, under GLP conditions and following the OECD 405 Guideline, the test item (95% purity) showed almost no irritant potential to the eye.

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:

weight of evidence

Study period:

August 1994 to December 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

July 31, 1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 17, 1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, D-97633 Sulzfeld
- Weight at study initiation: 2.4 - 2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): Altromin 2023 diet for rabbits, ad libitum
- Water (e.g. ad libitum): tap water from an automatical watering system, ad libitum
- Acclimation period: 6 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 (average)
- Humidity (%): 50 (average)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light):12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated control areas on each animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

6 d

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on dorsal area of the trunk
- Type of wrap if used: cellulose patch with test substance was applied to the test site and held in place by fixing marginally with non irritating tape (Blendern Wundpflaster, 3M). The application site was covered by a dressing (Fixomull Stretch, Fa. Beiersdorf). Access by the animal to the application site was prevented by a plastic collar.

REMOVAL OF TEST SUBSTANCE
- At the end of the exposure period the dressing, the tape with the patch and the collar were removed. Residual test substance was wiped off using wet cellulose tissue.

SCORING SYSTEM: according to OECD guideline 404

Irritation parameter:

erythema score

Basis:

animal: #1, #2

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal: #1, #2

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean 24, 48, 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 d

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

1/3 animals showed slight edema (grade 2) after 1 h, which was not present any more at the 24 h observation. The same animal showed very slight erythema (grade 1) at the 1, 24, 48 and 72 h observation. An additional examination at day 6 showed full reversibility.

Other effects:

no general toxic effects were noted

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 4
60 min	0/0/1	0/0/2
24 h	0/0/1	0/0/0
48 h	0/0/1	0/0/0
72 h	0/0/1	0/0/0
Average 24h, 48h, 72h	0/0/1	0/0/0
6 d	-/-/0	-/-/0

-      = no further examinations

Interpretation of results:

GHS criteria not met

Conclusions:

In this study 3,5,5-Trimethyl-ethyl capronate shows a very low irritant potential to the Skin and can be regarded as not classified for Skin Irritation according to GHS criteria

Executive summary:

In a primary dermal irritation study according to OECD guideline 404 (July 17, 1992) and EU method B.4 (July 31, 1992) 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of undiluted 3,5,5-Trimethyl-ethyl capronate (>90% a.i.) for 4 hours to 6 cm² body surface area. Animals then were observed for 6 days.  Irritation was scored by the method of Draize.

1/3 animals showed slight edema (grade 2) after 1 h, which was not present any more at the 24 h observation. The same animal showed very slight erythema (grade 1) at the 1, 24, 48 and 72 h observation. An additional examination at day 6 showed full reversibility.

Mean erythema scores from observations at 24, 48 and 72 h after patch removal were 0/0/0; mean edema scores were 0/0/1 for all three animals.

In this study, 3,5,5-Trimethyl-ethyl capronate was practically not irritating to rabbit skin.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

29.12.1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Feb. 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Mol:Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Möllegaard Breeding and Research Centre Ltd., Ejby, DK-4623 Lille Skensved
- Weight at study initiation: 2.2 - 2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): pellets "Altromin 2123" from Altromin, ad libitum
- Water (e.g. ad libitum): tap water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth, ad libitum
- Acclimation period: at least 1 wk

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3
- Humidity (%): 55±15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light):12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

the eyes were rinsed after the 24 h observation

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing with 20 mL 0.9% sodium chloride solution
- Time after start of exposure: 24 h

SCORING SYSTEM: according to OECD guideline 405

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #3

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

other: mean 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after application the conjunctivae of all animals were injected (conjunctival redness, grade 1). Additionally 1/3 animals showed a slight swelling (chemosis, grade 1). Discharge (grade 1) was observed in all animals.
Conjunctival redness, grade 1 was present in 1/3 animals at the 24 h observation. The other two animals showed no reactions. No reactions of the eyes were observed in any of the animals 48 and 72 hours after application.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study 3,5,5-Trimethyl-ethyl capronate was not irritating to rabbit eye.

Executive summary:

In a primary eye irritation study according to OECD guideline 405 (Feb. 1987) and EU Method B.5 (29.12.1992) 0.1 mL of 3,5,5-Trimethyl-ethyl capronate (95% a.i.) was instilled into the conjunctival sac of the left eye of 3 young adult female Mol:Russian rabbits for 24 h (the eyes were rinsed after the 24 h observation). Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

One hour after application the conjunctivae of all animals were injected (conjunctival redness, grade 1). Additionally 1/3 animals showed a slight swelling (chemosis, grade 1). Discharge (grade 1) was observed in all animals.

Conjunctival redness, grade 1 was present in 1/3 animals at the 24 h observation. The other two animals showed no reactions.

No reactions of the eyes were observed in any of the animals 48 and 72 hours after application.

In this study 3,5,5-Trimethyl-ethyl capronate is not an eye irritant.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin Irritation/corrosion:

Based on the study report R9400861 (1994, Klimisch 1), the test item shows a very low irritant and reversible response. Scores are clearly below the thresholds defined in GHS and in CLP to classify one substance as skin irritant. Therefore the registered substance is considered to be not classified for skin irritation.

 

Furthermore, in the study report RT 920350 (1992, Klimisch 2), the test item also shows irritation scores below the threshold for classification.

In this report, the irritant classification is derived from the irreversibility rather than the severity of the effects observed. However, it is unclear if this irreversibility is due to the test item as the effects triggering such classification only appear on day 21. Therefore such effects observed are not taken into account to derive the classification of the registered substance.

In conclusion, in view of the unclear effect observed in the study report RT 920350 (1992, Klimisch 2), the classification is derived from the fully reliable test R9400861 (1984, KL1).

Eye Irritation:

Based on the key study report R 95 01068 (1995, Klimisch 1), the test item shows a very low irritant and reversible response. Scores are clearly below the thresholds defined in GHS and in CLP to classify one substance as eye irritant. Therefore the registered substance is considered to be not classified for eye irritation.

Furthermore, the study report R 9500905 (1195, Klimisch 2) confirms the low irritant potential to the eye of the registered substance.