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Description of key information

A skin irritation study on eugenol has demonstrated that the compound is not irritating to rabbit skin (Toxicol Laboratories Limited, 1988).
An eye irritation study on eugenol has demonstrated that the compound has an irritant effect; however, this effect appears to decrease over the 7-day observation period (Troy, 1977).
No respiratory irritation was observed during the acute inhalation toxicity study (Clark, 1988).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

The potential of eugenol to cause skin and eye irritation was evaluated in 2 key studies in New Zealand White rabbits. The skin irritation study was compared to OECD Guideline No. 404 and the eye irritation study was compared to OECD Guideline No. 405. The skin irritation study was conducted according to Good Laboratory Practices (GLP); however, the eye irritation study was not compliant with GLP.

 

In the key skin irritation study, the skin (clipped free of hair) of 4 female New Zealand rabbits was exposed to 0.5 mL of eugenol under semi-occlusive conditions (Toxicol Laboratories Limited, 1988). Animals were exposed to the test article for 4 hours and observed over a 7-day period. The mean score for erythema was 1.9 out of 4 and the mean score for oedema was 1.0 out of 4 at time points up to the 72-hour observation. Two animals showed some erythema and oedema at the 7-day observation. No scores at any time point were greater than 2. No other test article-related findings were reported by the study authors. Based on the observations (less than a score of 2), the study authors concluded that eugenol is not an irritant.

 

In the key eye irritation study, 0.1 mL of eugenol was instilled into the conjunctival sac of the right eye of each of 6 female New Zealand White rabbits (Troy, 1977). Animals were exposed to the test substance for 24 hours and observed over a 7-day period. The overall eye irritation score decreased from 54 (out of a possible 110) on Day 1 to a score of 3 (out of a possible 110) on Day 7; however, full reversal of effects was not complete after 7 days. No other test article-related findings were reported by the study authors. Based on the results of this study, the investigators stated that the test article appeared to affect the rabbit eyes one day following application; however, the effects appeared to be reversible as the eye irritation grades decreased over the 7-day observation period.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available, GLP-compliant and of high quality (Klimisch score = 2).

Justification for selection of eye irritation endpoint:
Only one study available, of high quality (Klimisch score = 2) although conducted pre-GLP.

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP4.

Self classification:

Skin irritation:

The submission substance has a mean value of <2.3 for erythema or for oedema for all 4 animals from gradings at 24, 48, and 72 hours. While the recovery period did not extend to 14 days, there were signs of recovery after 7 days in 3 out of 4 animals; only 1 out of 4 animals had signs of continued irritation and slight scaling after 7 days. There was no pronounced variability in the response among the animals. 

As a result, the substance does not meet the criteria for classification according to the Annex VI of the Regulation (EC) No 1272/2008 and of the Directive 67/548/EC.

Eye irritation:

The eye irritation information available for the submission substance is based on the standard Draize scale which has an overall score based on a 110 point rating scale. This rating scale is not directly compatible with Regulation (EC) No 1272/2008 or Directive 67/548/EC classification criteria. However, based on guidance from various agencies, the submission substance appears to be severely irritating in the first 24 hours post-exposure, moderately to mildly irritating after 24 and 72 hours post-exposure, and practically non-irritating after 7 days post-exposure.

As a result, the substance meets the criteria for classification as eye irritant:

- Category 2 (H319: Causes serious eye irritation) according to Regulation (EC) No 1272/2008

- Xi; R36 (Irritating to eyes) according the Directive 67/548/EC.

Respiratory irritation:

During the macroscopic examination of the acute inhalation toxicity study, dark red slightly raised areas were detected in the lungs of one low- and one high-dose animals. However, the effect does not appear to be dose-related and was only observed in a limited number of animals. Moreover, no histopathological changes related to the macroscopic findings were detected. Gasping was recorded in some animals of the high-dose group but was fully reversible within 2 hours.

As a result, Eugenol does not meet the criteria for classification for respiratory tract irritation according the Regulation (EC) No 1272/2008 and the Directive 67/548/EC.

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