Registration Dossier

Administrative data

Description of key information

A skin irritation study is available which was conducted to a test protocol that is similar to the appropriate OECD guideline but pre-dates GLP. The study reports the test material 2,2,4,4,6,6-hexamethylcyclotisilazane to be irritating to skin (Rhône-Poulenc, 1973). Additional non-standard studies indicate that the substance is corrosive to skin. On the basis of the available weight of evidence, the substance is classified as corrosive.

The key eye irritation study was chosen, because it was the most recent available study, conducted to a test protocol that is comparable to the appropriate OECD test guideline, but pre-dates GLP. The study reports the test material, 2,2,4,4,6,6-hexamethylcyclotisilazane, to be not irritating to eyes (Rhône-Poulenc, 1973).

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 study available

Additional information

Three studies are available for skin irritation/corrosion endpoint. In a study conducted according to a protocol similar to OECD 404, but not in compliance with GLP, application of undiluted substance to the intact skin of six New Zealand white rabbits for 24 hours resulted an erythema score of 4/4 in all animals at 24 and 72 hours (Rhône-Poulenc, 1973). No further observations were made and there is no information on reversibility of the observed erythema. Edema (score 1/4) was observed in three out of six animals at 24 hours, fully reversible within 72 hours. Test substance diluted in oil also resulted in erythema, but not edema. A 30% solution in peanut oil also resulted an erythema score of 4/4 in all animals at 24 and 72 hours. A 10% solution caused erythema in five out of six rabbits, with a score of 3/4 at 24 hours increasing to 4/4 at 72 hours. No erythema was observed at 24 hours after application of a 3% solution.

Two non-standard studies are also available, which add weight of evidence for skin irritation/corrosion (Dow Corning Corporation, 1969).

In the first study (Dow Corning Corporation, 1969), undiluted test material was applied to intact skin of the ear and belly in rabbits for 24 hours. Slight erythema followed by moderate necrosis and scab formation were evident when the test substance was applied twice to intact skin of the ear for 24 hours. Deep necrosis and scab formation were noted when the test material was applied to once intact skin of the belly for 24 hours. The study reports the test material to be severely irritating to skin.

The second study (Dow Corning Corporation, 1970), undiluted test material was applied onto intact and abraded skin of rabbits for 5 minutes, 1 hour and 24 hours. Deep necrosis was evident in all of the test animals after each application of the test material. The study reports that the test substance caused severe damage to skin.

The registration substance was also tested in a dose range finding study for skin sensitisation (see Section 7.4). The main study was terminated due to adverse effects observed in the test animals, but it was conducted according to an appropriate OECD test guideline, and in compliance with GLP (Eurofins, 2016).

Following a 6-hour occluded topical application of 25, 50, 75 and 100 % test substance in dry acetone to the flanks of 2 guinea pigs, signs of systemic toxicity and severe skin irritation (necrosis) were observed in all of the animals. One animal, treated with 2.5 and 5.0 % of test substance, showed grade 2 erythema, which was evident after 72 hours. One animal, treated with 0.5 and 1.0 % test substance, showed grade 1 erythema which was fully reversible within 72 hours.

In combination with the results of historical skin irritation studies, the findings of the sensitisation sighting study were taken as evidence that the registration substance should be classified as corrosive to skin. As such, it is considered that further testing for skin irritation/corrosion is not appropriate despite the fact that the available studies do not meet current guideline standards. There is sufficient evidence to classify the substance as Corrosive Category 1.


The key eye irritation study was chosen, because it was the most recent available study, conducted to a test protocol that is comparable to the appropriate OECD test guideline, but not compliant with GLP. The study reports the test material, 2,2,4,4,6,6-hexamethylcyclotisilazane, is not irritating to eyes (Rhône-Poulenc, 1973).

Application of 0.1 ml of undiluted test substance to the eyes of six New Zealand white rabbits resulted in conjunctival scores (mean of 24, 48 and 72 hours) of between 0 (two animals) and 1.67 (one animal). Chemosis scores (mean of 24, 48 and 72 hours) were between 0 (2 animals) and 0.67 (2 animals). No effects on iris or cornea were observed in any animal at any timepoint (Rhône-Poulenc, 1973).

Two non-standard studies are also available (Dow Corning Corporation 1969 and 1970).

In the first study, application of test material into eyes of rabbits caused moderate pain, conjuctivitis and corneal response in both washed and unwashed eyes after application (Dow Corning Corporation, 1969). The severity of the eye reaction was not determined. All responses subsided within 48 hours. The study concludes that the test substance has a slight irritating effect on eyes. The irritation category could not be determined due to lack of information on scoring system used to assess the eye reaction.

In the second study, application of test material into the eyes of rabbits caused moderate pain, iritis, conjunctivitis and slight corneal response, which essentially subsided within 48 hours when the eyes were washed after exposure (Dow Corning Corporation, 1970). Moderate conjuctivitis, iritis with moderate to severe corneal injury were evident within 7 days post-exposure when no washing after application was performed. The study concludes that the test material is irritating to eyes.

Based on the available information, it is not possible to conclude on the classification category for eye irritation. However, since the substance is classified as corrosive to skin, it is neither appropriate nor necessary to perform additional testing for the eye irritation endpoint.

Justification for classification or non-classification

Based on expert judgment from the available skin irritation studies and skin sensitisation sighting study, it is concluded that 2,2,4,4,6,6-hexamethylcyclotrisilazane is classified as Corrosive Category 1C (Skin Corr. 1, H314: Causes severe skin burns and eye damage) according to the criteria of Regulation (EC) No. 1272/2008.