Reaction mass of 2-(1,1-dimethylethyl)-4-{[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio}-5-methylphenyl 3-(dodecylthio)propionate and thiobis[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene] bis[3-(dodecylthio)propionate]

Endpoint summary

Description of key information

The Primary Irritation Index for skin irritation was calculated to be 0.0; AO-26 was classified as ‘non-irritant’ according to the criteria of the ECETOC and did not require labelling in accordance with Commission Regulation 1272/2008.

The highest total mean score was 4.7 occurring at the 1 hour observation; accordingly under the criteria Kay and Calandra (1962) AO-26 was classified as “minimally irritating” to the eye however AO-26 does not require classfcation or labelling in accordance with European Commission regulation 1272/2008.

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

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain.
- Age at study initiation: 38 weeks
- Weight at study initiation: 3.91 to 4.43 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): 125 g of a standard laboratory rabbit diet per day
- Water (e.g. ad libitum):Drinking water was provided ad libitum.
- Acclimation period:All rabbits were acclimatised to the experimental environment for a period of 21 weeks prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light):Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

Approximately 0.5 mL of the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites on three animals.

Duration of treatment / exposure:

Three minutes, one and four hours

Observation period:

1, 24, 48 and 72 hours later.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorso-lumbar region of each rabbit
- % coverage: 25 mm x 25 mm
- Type of wrap if used: porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites on three animals.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 72 hours

OBSERVATION TIME POINTS (hours): 1, 24, 48 and 72

SCORING SYSTEM:
- Method of calculation: A primary irritation index (PII) was calculated from the erythema and oedema scores.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Interpretation of results:

GHS criteria not met

Conclusions:

There was no sign of toxicity or ill health in any rabbit during the observation period. No dermal reaction was observed in any animal throughout the duration of the study.

Executive summary:

The Primary Irritation Index was calculated to be 0.0; AO-26 was classified as ‘non-irritant’ according to the criteria of the ECETOC and did not require labelling in accordance with Commission Regulation 1272/2008.

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:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 40 weeks
- Weight at study initiation: 3.32 to 4.52 kg
- Housing: Each animal was housed individually in a plastic cage with perforated floors.
- Diet (e.g. ad libitum): 125 g of a standard laboratory rabbit diet per day
- Water (e.g. ad libitum): Drinking water was provided ad libitum.
- Acclimation period:All rabbits were acclimatised to the experimental environment for a period of 23 weeks prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):16 to 20°C
- Humidity (%):40 to 70%
- Photoperiod (hrs dark / hrs light):Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Three rabbits were each administered a single ocular dose of a volume of 0.1 mL of the test substance.

Duration of treatment / exposure:

The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated.

Observation period (in vivo):

The animals were returned to their cages and checked at least twice during the first hour after dosing and at regular intervals throughout the day to ensure no severe injury passed unnoticed. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours after treatment.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Kay and Calandra

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1h

Score:

4.7

Max. score:

4.7

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

0.7

Reversibility:

fully reversible

Irritant / corrosive response data:

Injection of the conjunctival blood vessels, very slight chemosis and slight discharge were apparent in the sentinel animal one hour after instillation; the conjunctival injection persisted throughout the first 48 hours after instillation. The treated eye was overtly normal 72 hours after instillation. Injection of the conjunctival blood vessels with slight discharge was evident in the remaining animals one hour after instillation; the treated eyes of these animals were overtly normal 24 hours after instillation. Instillation of the test material gave rise to practically no initial pain response.

Interpretation of results:

GHS criteria not met

Conclusions:

There was no sign of toxicity or ill health in any rabbit during the observation period.

Executive summary:

The highest total mean score was 4.7 occurring at the 1 hour observation; accordingly under the criteria Kay and Calandra (1962) AO-26 was classified as “minimally irritating” to the eye however AO-26 does not require classfcation or labelling in accordance with European Commission regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

AO-26 is considered as not classified for Skin and Eye irritiation and does not require labelling in accordance with European Commission regulation 1272/2008.