Registration Dossier

Administrative data

Description of key information

- Highly irritating to skin

- Moderately irritating to eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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

Skin Irritation/Corrosion Potential

The potential of the substance to elicit skin irritation/corrosion was evaluated in two in vivo experimental studies on rabbits, both performed according to methods which are comparable to the OECD Guideline 404. As in vivo experimental data is available, an in vitro assessment is not required.

(1) In the first study, the test item was applied as is to both an intact site and an abraded site of six New Zealand white rabbits, and the sites were monitored for erythema and oedema according to the Draize scale, at 24 and 72 hours after application.

All six animals demonstrated an erythema score of 4.0 at both the 24 hour and the 72 hour monitoring of both the intact and the abraded skin sites. Four out of the six animals demonstrated an oedema score of 3.0 at 24 hours on both the intact and abraded sites; the remaining two animals had a score of 4.0 at the same sites and times. At 72 hours, all six animals demonstrated an oedema score of 2.0 at both the intact and abraded sites. Reversibility of erythema and oedema was not monitored beyond 72 hours in this study. Based on these findings, the substance was considered severely irritating to rabbit skin.

For evaluation using the CLP regulation, it is necessary to calculate the mean erythema and oedema scores at 24, 48 and 72 hours for each animal at the intact site only. As no data for the 48 hour interval was recorded in this study, the mean was calculated using a worst-case approach, whereby the more severe of the 24 or 72 hour scores in place of the 48 hour score. The mean (24/48/72 h) erythema scores were 4.0 for all 6 animals; the mean (24/48/72 h) oedema scores were 2.67 for 4 animals, and 3.33 for 2 animals.

(2) In the second study, 0.5 mL of test item was applied, as-is, to a 2.5 cm2area of skin at the centre of the trunk of 6 rabbits and covered with an occlusive surgical gauze pad encased with waterproof wrapping and adhesive tape, for a total of four hours, after which time the test item was washed away and the site was subsequently evaluated for erythema and oedema immediately, after 48 hours, and at 7 days, according to Draize scores for irritation. Body weights were also assessed at the start and end of the study period.

All animals experienced a negligible weight loss over the study period. Mean erythema scores of all animals were 1.8 after washing (range: 1.0 to 2.0), 2.0 after 48 hours (range: 1.0 to 3.0) and 2.5 after 7 days (range: 1.0 to 3.0). Mean oedema scores of all animals were 1.7 after washing (range: 1.0 to 2.0), 1.8 after 48 hours (range: 1.0 to 4.0) and 2.7 after 7 days (range: 1.0 to 3.0). Based on these findings, the substance is considered moderately irritating to rabbit skin.

Interestingly, the effect is more relevant after 48 hours than after 4 hours. A possible explanation is that the effect on the skin is caused by the formation of phopshorous acid as a consequence of the degradation of the product in contact with humidity.

Conclusion: Although both studies evaluate skin irritation potential, the first study provides readings more applicable to the requirements of the CLP Regulation and provides more detailed experimental procedure, whereas the second study does not evaluate erythema and oedema at two out of the three time points required for classification purposes. For this reason, the first study is considered the key study for evaluating skin irritation potential, showing severe skin irritatin potential, and the moderately irritating effects seen in the second study support these findings.

Eye Irritation/Damage Potential

The eye irritation potential of the substance was evaluated in an experimental study performed according to the criteria specified in paragraph 191.12 of the final Order, Enforcement regulations, federeal regulation, federal registror vol. 29, N 192, P.13009, 17 september 1964, a method similar to the OECD Guideline 405. As in vivo experimental data is available, an in vitro assessment is not required. The test item was applied directly into the the eye of three albino rabbits and the site was monitored for corneal opacity, iritis, conjunctival redness and chemosis according to Draize scores, immediately after application and then at 1, 2, 3 and 7 days after application.

Corneal opacity scores were 1.0 in all animals at all time points, with the exception of the 7 day reading, which was 0.0 in two out of the three animals. Iritis scores were 1.0 in all animals both immediately after application and after 1 day; 2 days after application, the iritis scores were 0.0 for two animals and 1.0 for one animal, after which time the iritis scores were 0.0 for all animals until end of study period. Conjunctival redness scores were 2.0 in all animals immediately after application; 1.0 in all animals after both 1 and 2 days; 0.0 (1 animal) and 1.0 (2 animals) after 3 days, and 0.0 among all animals after 7 days. Conjunctival chemosis scores were 2.0 among all animals immediately after application; 1.0 among all animals after 1 day; and 1.0 (2 animals) and 0.0 (1 animal) after 2 days; all animals had scores of 0.0 after 3 and 7 days.

The mean (24/48/72 hour) scores for the four parameters examined can be interpreted for each animal as follows: corneal opacity = 1.0 (all animals); iritis = 0.33 and 0.67 (2 and 1 animals, respectively); conjunctival redness = 0.67 and 1.0 (1 and 2 animals, respectively); chemosis = 0.33 and 0.67 (1 and 2 animals, respectively).

It is apparent that the test item is irritating to the rabbit eye, however, it should be noted that all parameters were reversible within a 7-day window with the exception of a corneal opacity score of 1.0 in one rabbit only after 7 days.

Justification for classification or non-classification

Skin Irritation/Corrosion Criteria

According to Annex I: 3.2.2.1.1 of the CLP Regulation (EC) No. 1272/2008 for skin corrosion and irritation, a substance is classified as a Category 1: Skin Corrosive if it produces irreversible damage to the skin; namely, visible necrosis through the epidermis and into the dermis, in at least 1 test animal following the application of a test substance for up to 4 hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs, discolouration due to blanching of the skin after 14 days, complete areas of alopecia, and scars. Skin corrosives can be further divided into 3 sub-categories:

- Sub-Category 1A: corrosive responses in at least one animal following exposure ≤ 3 minutes during an observation period ≤ 1 hours

- Sub-Category 1B: corrosive responses in at least one animal following exposure > 3 minutes and ≤ 1 h and observations ≤ 14 days

- Sub-Category 1C: corrosive responses in at least one animal after exposures > 1 hour and ≤ 4 hours and observations ≤ 14 days

A substance is classified as a Category 2: Skin Irritant if:

(i) it produces reversible damage (mean score of ≥ 2.3 and ≤ 4.0 for erythema and/or oedema at 24, 48 and 72 hours after removal) following the application of a test substance for ≤ 4 hours in at least 2 of 3 tested animals; or

(ii) it produces inflammation that persists to the end of an observation period of 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(iii) very definite positive effects related to chemical exposure are apparent in a single animal but it does not meet the criteria above.

According to the in vivo key study, the substance was found to be irritating to rabbit skin, but not corrosive. Scores for erythema were 4 among all animals for the 24/48/72 hour mean. Although numerical data beyond 72 hours was not presented in the study report, the effects were described as reversible. The mean irritation scores for the test item satisfy the abovementioned criteria for Category 2: Skin Irritant, H315, according to the CLP Regulation (EC) no. 1272/2008.

Eye Irritation/Corrosion Criteria

According to Annex I: 3.3.2.1.1 and Annex I: 3.3.2.1.2 of the CLP Regulation (EC) No. 1272/2008 for serious eye damage and eye irritation, a substance is classified as Category 1: Serious Eye Damage if it produces:

(i) effects on the cornea, iris or conjunctiva which are not reversible within 21 days in at least one animal, and/or

(ii) a positive response of corneal opacity (mean score ≥ 3) or iritis (mean score > 1.5) in at least 2 of 3 animals following grading at 24, 48 and 72 hours after application of the test material to the anterior surface of the eye.

A substance is classified as a Category 2: Eye Irritantif:

- it produces a positive response of corneal capaity (mean score 1), iritis (mean score 1), conjunctival redness (mean score 2) and/or chemosis (mean score 2) in at least 2 of 3 animals following grading at 24, 48 and 72 hours after application of the test material to the anterior surface of the eye which is fully reversed within 21 days.

According to the in vivo study available, corneal opacity scores met the threshold value for classification in Category 2 as an eye irritant. However, the reversibility of the irritation cannot be ruled out, as the study was terminated at 7 days instead of the required 21 days, with positive (although slight) irritation value still persistent in one animal. Based on this consideration, the substance is classified at lease as a Category 2: Eye Irritant, H319, according to the CLP Regulation (EC) No. 1272/2008.