Registration Dossier

Administrative data

Description of key information

In the key acute oral toxicity study in mice, conducted according to a protocol similar to OECD TG 401, but not in compliance with GLP, the LD50 value for the test substance, 2,2,4,4,6,6-hexamethylcyclotrisilazane, was concluded to be 1700 mg/kg bw (Rhône-Poulenc, 1973).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 700 mg/kg bw
Quality of whole database:
The study was the most recent study available, conducted according to a protocol similar to OECD TG 401 with no clear information on GLP compliance.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key acute oral toxicity study in mice, conducted according to a protocol similar to OECD TG 401, but not in compliance with GLP, the LD50 value for the test substance, 2,2,4,4,6,6-hexamethylcyclotrisilazane, was concluded to be 1700 mg/kg bw (Rhône-Poulenc, 1973).

2,2,4,4,6,6-Hexamethylcyclotrisilazane was administered to three male and three female mice at doses of 670, 1000, 1500, 2250 and 3370 mg/kg bw in peanut oil. No mortalities occurred in any of the test animals treated with 670 and 1000 mg/kg bw of the test substance.

After ten days, the mortalities in the other groups were as follows: 1500 mg/kg bw three out of six; 2250 mg/kg bw four out of six; 3370 mg/kg bw six out of six. At all doses tested the animals showed slight sedation, stiffness and increased sensitivity to sound and touch. At toxic doses death followed tonic convulsions, appearing during the first 24 hours. Animals which survived were symptom-free after two days.

Two supporting acute oral studies were also available. Neither study meets current guideline requirements; they do, however, add weight of evidence for acute toxicity and support the findings of the key study (DCC, 1969; DCC, 1970). The first supporting study (DCC, 1969) reported LD50 value of <500 mg/kg bw in rats, where no mortality was observed after administration of 0.252 g/kg. All animals died after administration of 0.50, 1.00, 2.00, 3.98 g/kg. The second supporting study (DCC, 1970) reported LD50 value of <1000 mg/kg bw in rats, where no deaths occurred following administration of 0.1 g/kg test substance. All animals died after administration of 1.0 and 10.0 g/kg test substance.

Two supporting acute inhalation studies were also available. The first study (DCC, 1989), conducted according to an appropriate OECD test guideline with acceptable restrictions and under GLP, did not report any mortality or clinical signs of toxicity during the 14-day study period, therefore the LC50 value would be greater than the tested concentration (≥4.9 mg/l). The restrictions were that the test concentration was not the maximum test concentration for vapours as stated in the guideline, and analytical verification of the test concentration was not performed. The second study (DCC, 1969), which did not meet current guideline requirements, concluded that the test substance, 2,2,4,4,6,6 -hexamethylcyclotrisilazane caused eye and nose irritation during 7-hour exposure.

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 (refer to Section 7.3), 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 acute oral toxicity is not appropriate despite the fact that the available acute studies do not meet current guideline standards. There is sufficient evidence to classify the substance as harmful via oral exposure.


Justification for classification or non-classification

Based on the available data for, 2,2,4,4,6,6-hexamethylcyclotrisilazane, classification for Acute Toxicity Category 4, 'H302: Harmful if swallowed' is required according to Regulation (EC) No. 1272/2008.

In addition, classification for Specific Target Organ Toxicity following a single exposure (STOT SE 3) is applicable for respiratory irritation, H335: May cause respiratory irritation.