Reaction mass of dodecyltrimethylammonium bromide and tetradonium bromide

Endpoint summary

Description of key information

Read-across data on acute oral toxicity of tetradonium bromide (C14 TMAB) in rats indicate LD50 value of 390 mg/kg bw.

Read-across data for acute dermal toxicity on cetrimonium chloride (C16 TMAC) in rabbits. A dermal LD50 value of 4.3 ml/kg bw was found for cetrimonium chloride (corresponding to 2150 mg/kg bw ).

Read-across data for acute inhalation toxicity on cetrimonium bromide (C16 TMAC) includes a 30 minutes inhalation study with mice. The study indicates pulmonary irritation as dose-related reduced tidal volume and increase in respiratory frequency was found with a LOEC of 1.8 mg cetrimonium bromide/m3 and a NOEC of 0.57 mg cetrimonium bromide/m3. Initial signs of pulmonary inflammation were found at 19 mg cetrimonium bromide/m3 based on an increase in macrophages in BAL.

See attached read-across justification in section 13.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

390 mg/kg bw

Quality of whole database:

Klimisch Score 1, as all reported parameters are closely comparable to guideline.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1.8 mg/m³

Quality of whole database:

Klimisch score 2

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 150 mg/kg bw

Quality of whole database:

Klimisch score 2

Additional information

Justification for selection of acute toxicity – oral endpoint
Read-aross to data on tetradonium bromide. The study is an oral acute toxicity study with rats similar to OECD 401 but with an initial range finding study for a more exact establishment of LD50.

Justification for selection of acute toxicity – inhalation endpoint
Read across to available study concerning inhalation of cetrimonium bromide. Non-guideline study determining pulmonary irritation and inflammation in mice after 30 minutes of exposure. The observed effects considered relevant for classification for respiratory (pulmonary) irritation, STOT SE3; H335.

Justification for selection of acute toxicity – dermal endpoint
Read across to available dermal acute toxicity study on cetrimonium chloride. No evidence for classifcation for acute dermal toxicity applies according to the CLP critera.

Justification for classification or non-classification

Read-across to C12 -14 TMAB is made from data on C14 TMAB, C16 TMAC and C16 TMAB (see read-across justification attached in section 13).

Data on acute oral toxicity of tetradonium bromide, indicate that tetradonium bromide should be classified as Acute tox 4; H302 for acute oral toxicity.

A dermal LD50 value of 4.3 ml/kg bw was found for cetrimonium chloride (corresponding to 2150 mg/kg bw ), which is above the CLP classification criteria.

Read-across from data on acute inhalation toxicity on cetrimonium bromide indicates that tetradonium bromide should be classified as STOT SE3; H335. A 30 minutes inhalation study with mice indicates pulmonary irritation as dose-related reduced tidal volume and increase in respiratory frequency was found with a LOEC of 1.8 mg cetrimonium bromide/m3 and a NOEC of 0.57 mg cetrimonium bromide/m3. Initial signs of pulmonary inflammation were found at 19 mg cetrimonium bromide/m3 based on an increase in macrophages in BAL.

However, no mortality were noted at rather low dose levels used (up to 19 mg/m3), thus, data are not sufficient and conclusive regarding assessment of acute toxicity by inhalation.