Quaternary ammonium compounds, trimethylsoya alkyl, chlorides

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The vapour pressure of the test substance was determined using the isothermal thermogravimetric effusion method, according to EU Method A.4 (Boerdijk, 2018).

Vapour pressure:

0 Pa

at the temperature of:

20 °C

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The appearance and physical state of the test substance were characterised according to US EPA OPPTS 830.6303 (Andersson, 2018).

Physical state at 20°C and 1013 hPa:

solid

Form:

cream / paste

Colour intensity:

light

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Based on the results of the read across study, TMAC S is considered to be corrosive to skin and eyes.

Endpoint conclusion:

adverse effect observed (corrosive)

Endpoint conclusion:

adverse effect observed (irreversible damage)

Endpoint conclusion:

no study available

Skin

A study was conducted to determine the skin irritation potential of the read across substance, TMAC T (50% active) in rabbits, according to a method similar to OECD Guideline 204. Six rabbits (both sexes) were treated with 0.5 mL of undiluted read across substance (50% active ingredient) in an occlusive patch fixed with adhesive tape and wrapped with an impervious material, for 4 h. Observations were made at 4 h, 48 h and 10 days post-exposure. If the read across substance appeared to be corrosive after 4 h, another study was conducted with a 1 h exposure period under similar test conditions. The Draize scoring criteria was used for evaluating the corrosion potential. At 4 h, very slight to well-defined erythema, very slight ischemia and very slight oedema were observed, with an average irritation score of 4/8. At 48 h, there was well-defined to moderate erythema, very slight to slight ischemia and very slight or slight oedema and the average irritation score was 5.4/8. After 10 days, slight to distinct incrustation and decreased hair growth was observed. After an exposure period of 1 h, very slight erythema was observed with an average irritation score of 0.85/8. After 48 h, there was very slight to moderate erythema and very slight or slight oedema and the average irritation score was 1.25/8. No skin effects were observed after 10 days. Under the study conditions, the undiluted read across substance (50% active ingredient) was corrosive after 4 h of occlusive exposure. Based on the results of the read across study, similar corrosive potential is expected for the test substance.

 

An OECD 439 guideline compliant in vitro skin irritation study on the test substance was identified to be reported in a SCCS opinion on Soytrimonium chloride (Colipa no. 72). In this study, the test substance (active: 60.3%) was applied undiluted as well as 5% v/v solution in sterile water (i.e., equivalent to 60.3 and 3.015% a.i.) in an in vitro Reconstituted Human Epidermis Model (Episkin). Tissues were exposed to the test substance for 15 minutes followed by a 42 h observation period. No cytotoxicity was induced at both the test concentrations. The relative mean viability was 106.3 ± 4.8% for the undiluted material and 121.3 ± 1.1% for the diluted material. Histological evaluation showed no to minimal epidermal effects with the 5% (3.015% a.i.) solution. The neat material also resulted in no to minimal epidermal effects in two tissues, with the third tissue showing slight epidermal effects. In general, the histopathological evaluation confirmed the absence of cytotoxicity in the MTT section of the study at both concentrations. Under the study conditions, the test substance was concluded to be slightly irritating to the skin (SCCS, 2012). The results from the in vitro test are considered to be questionable as the RHE test model are recognised to be not applicable for all groups of chemical classes specifically for the fatty amine derivatives, where RhE assays did not predict corrosivity, whereas these substances were corrosive in in vivo rabbit studies (Houthoff et al., 2014 cited in the ECHA R.7a guidance, 2017).

 

Based on the above information and the results from the in vivo read across study, the test substance is considered to be corrosive to skin.

 

 

Eye

Data waiving: A study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1).

 

This is further supported by an OECD 438 guideline compliant in vitro eye irritation study on the test substance which was identified to be reported in a SCCS opinion on Soytrimonium chloride (Colipa no. 72). In this study, isolated chicken eyes were exposed to the test substance for 10 seconds, which were followed by evaluations at 0, 30, 75, 120, 180 and 240 minutes. The test substance was applied on cornea either undiluted or at a concentration of 5% (i.e., equivalent to 60.3 and 3.015% a.i.). The undiluted test substance produced severe irritation with an irritation index of 141/200. Histological examination of the corneas revealed moderate erosion of the epithelium with no effects on the stroma and endothelium being observed. The 5% (v/v) aqueous dilution of the test substance caused very slight swelling (5%), slight opacity (1.0) and slight to moderate fluorescein retention (1.5). The calculated Irritation Index was 55/200. Histological examination of the corneas treated with the diluted material revealed very slight or slight erosion of the epithelium, with no effects on the stroma and endothelium being observed. Under the study conditions, the undiluted test substance induced irreversible effects on the eye and serious damage to the eye, while the 5% (v/v) aqueous dilution was evaluated to cause only minimal or transient irritation. Therefore, the test substance was concluded to be corrosive to eyes (SCCS, 2012).

Based on the results of thein vivoskin and eye irritation studies, the test substance warrants a ‘Skin Corr. 1C; H314: Causes severe skin burns and eye damage’ as well as serious eye damage, ‘Eye dam. 1; H31: Causes serious eye damage’ classification according to the EU CLP criteria (Regulation EC 1272/2008). Labelling for this endpoint is covered by the above classifications for skin effects. 

With regard to respiratory tract irritation, although TMAC S is a very corrosive substance, its low vapour pressure prohibits the occurrence of respiratory irritation by vapour. Further, the classification of corrosive is already considered to implicitly cover the potential of RTI; therefore an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5).