Hexadecyl acetate

Endpoint summary

Description of key information

Skin: Pre-GLP animal investigation concluding that the test item was a mild irritant to skin supported by human data showing that a test material declared to contain 90 % of the test item was incapable of acting as a primary irritant in any of 53 volunteers who took part in the study.
Eye: Two pre-GLP studies demonstrating that a test material declared to contain 90 % of the test item did not cause classification as an eye irritant when instilled into the eyes of rabbits.

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:

key study

Study period:

December 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

investigation took place prior to introduction of GLP

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

- The investigation was conducted on six adult albino rabbits selected from healthy, acclimated, animals.

Type of coverage:

semiocclusive

Preparation of test site:

other: abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL or 0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

Six

Details on study design:

- The back of each animal was shaved free of hair.
- Intact skin was exposed on the left half of the shaved area.
- The right side of the shaved area was abraded.
- Test material (0.5 mL or 0.5 g) was introduced under a square patch of surgical gauze measuring 1 inch x 1 inch.
- Patches were removed after 24 hours and observations recorded.
- Further observations were made after 72 hours.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 h

Score:

1.17

Max. score:

4

Reversibility:

no data

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 72 h

Score:

1.33

Max. score:

4

Reversibility:

no data

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: intact skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 h

Score:

1.17

Max. score:

4

Reversibility:

no data

Remarks on result:

other: abraded skin

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 72 h

Score:

1.33

Max. score:

4

Reversibility:

no data

Remarks on result:

other: abraded skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 24 h

Score:

0.17

Max. score:

4

Reversibility:

no data

Remarks on result:

other: abraded skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

animals 1 to 6

Time point:

other: 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: abraded skin

Irritant / corrosive response data:

- Scoring of the effects produced by the test material is shown in Table 1 (attached).
- The test material produced erythema in all six animals with intact and abraded skin.
- The test material produced edema in one animal with abraded skin only.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the data presented, the test sample was considered to be a mild irritant to rabbit skin. Nevertheless, the scores for erythema and edema did not fall within the range requiring classification under the terms of Regulation (EC) No. 1272/2008 for 5 out of 6 animals over a period of 72 hours.

Executive summary:

METHOD

 

Acute skin irritation was investigated in the rabbit using a mixture declared to contain 90 % of test item.

RESULTS

The test material produced erythema in all six animals with intact and abraded skin. However, the test material produced edema in one animal with abraded skin only.

CONCLUSION

On the basis of the data presented, the test sample was considered to be a mild irritant to rabbit skin. Nevertheless, the scores for erythema and edema did not fall within the range requiring classification under the terms of Regulation (EC) No. 1272/2008 for 5 out of 6 animals over a period of 72 hours.

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

Study period:

July 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not applicable

GLP compliance:

no

Remarks:

investigation conducted prior to introduction of GLP

Species:

rabbit

Strain:

other: Albino

Details on test animals or tissues and environmental conditions:

- The study was conducted on six young adult albino rabbits selected from healthy, acclimated, animals according to the procedure described in 16 CFR 1500.42.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Not stated

Duration of treatment / exposure:

No washout

Observation period (in vivo):

Seven days

Number of animals or in vitro replicates:

Six

Details on study design:

- Ocular reactions were observed and recorded at 24, 48 and 72 hours after instillation of the test material (see scoring scheme, attached).
- The ocular reactions were also observed and recorded at 7 days after instillation of the test material.

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Animals 1 to 6

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Animals 1 to 6

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.89

Max. score:

3

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: Animals 1 to 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.39

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

other: Animals 1 to 6

Irritant / corrosive response data:

- Individual eye irritation scores are shown in the attached document.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was found to be a mild irritant to the rabbit eye when not followed by a washout after instillation. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for each of six animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis.

Executive summary:

METHOD

Acute eye irritation was investigated in the rabbit using a mixture declared to contain 90 % of test item.

RESULTS

Conjunctival effects were observed in all six animals but, with the exception of discharge, these effects cleared in five animals during the seven day observation period.

CONCLUSION

The test material was found to be a mild irritant to the rabbit eye when not followed by a washout after instillation. However, the test material is not classified under the terms of Regulation (EC) No 1272/2008 because the mean scores for each of six animals calculated using data from 24, 48 and 72 hour observations were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

 

In a pre-GLP study, acute skin irritation was investigated in the rabbit using a mixture declared to contain 90 % of test item. Observations and assessment took place at 24 and 72 hours.

 

The test material produced erythema in all six animals with intact and abraded skin. However, the test material produced oedema in only one animal with abraded skin. On the basis of the data presented, the test sample was considered to be a mild irritant to rabbit skin.

 

In a second study, involving 56 human volunteers, it was reported that the same test material was incapable of acting as a primary irritant in any of the individuals in the test panel. Furthermore, the test material did not elicit any visible response in 50 out of 53 to whom 50 % test material in petrolatum (equivalent to 45 % of the test item described in this dossier) was applied to the same dermal site for 24 hours on four consecutive days for a period of three weeks.

Eye

 

In two pre-GLP studies, acute eye irritation was investigated in the rabbit using a mixture declared to contain 90 % of test item.

 

The first study reported conjunctival effects in all six animals but, with the exception of discharge, the effects cleared in five animals during the seven day observation period. The test material was found to be a mild irritant to the rabbit eye when not followed by a washout after instillation.

 

The second study reported that the test material caused slight injection of the blood vessels in the eyes of one rabbit for 72 hours and in one rabbit for 48 hours. Swelling was barely perceptible in one rabbit after 24 hours. The test material was considered to be essentially non-irritating to the rabbit eye; or at worst, a very mild irritant.

Justification for selection of skin irritation / corrosion endpoint:
Meets generally accepted scientific standards, well documented and acceptable for assessment.

Justification for selection of eye irritation endpoint:
Meets generally accepted scientific standards, well documented and acceptable for assessment.

Justification for classification or non-classification

Skin: The available assessment of skin irritation in the rabbit did not include an assessment at 48 hours or an observation period. As a result, it is not possible to calculate the mean score for each animal from data recorded at 24, 48 and 72 hours or to compare that mean score against observations made at 7 or 14 days. Nevertheless, the scores for erythema and oedema did not fall within the range requiring classification for 5 out of 6 animals over a period of 72 hours. In conjunction with the results from application of the test material to the skin of human volunteers it is considered that the substance does not meet the criteria for classification as a skin irritant under the terms of Regulation (EC) No. 1272/2008.

 

Eye: The test material is not classified under the terms of Regulation (EC) No 1272/2008 because mean scores calculated using data from 24, 48 and 72 hour observations in two studies were below the stated limits for corneal opacity, iritis, conjunctival redness and chemosis for all animals.