Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid

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

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Skin irritation:
- neat substance: corrosive in rabbits (OECD TG 404, GLP): pure active substance (99.4% a.i.) applied to the intact skin for 4 hours, 1/3 animals was noted with full thickness destruction of the skin tissue at the 48- and 72-hour reading, mild to severe and early-onset signs of irritation in 2/3 animals (reversible in these animals within 14 d)
- 20% aqueous solution: irritating in rabbits (OECD TG 404, GLP): substance applied to the intact skin for 4 hours, 3/3 animals showed grade 4 erythema and grade 4 edema (reversible within 21 d)

Eye irritation:
- neat substance corrosive based on results from skin irritation study;
- 20% aqueous solution: irreversible effects to the eye in rabbits (OECD TG 405, GLP): grade 3 redness and lesions of the iris grade 2 were observed throughout the study period (72 hours), reversibility was not observed

- 1% aqueous solution: reversible effects to the eye in rabbits (OECD TG 405, GLP): mean grade 2 redness and chemosis was observed after 24/48/72 hour observation period, reversibility was not observed until 72 hours

Endpoint conclusion:

adverse effect observed (corrosive)

Endpoint conclusion:

adverse effect observed (irreversible damage)

Endpoint conclusion:

no study available

Skin irritation

Several tests for the skin irritation/corrosion potential are available for Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid.

Anhydrous active substance is not produced by the regular manufacturing process; the active substance as manufactured is the 20% aqueous solution.

The 20% a.i. aqueous solution of registration substance was first tested in 3 New Zealand White rabbits, according to EC method B.4 (1984) and OECD guideline 404 (1981). 0.5 mL of the test substance was applied to the intact skin of rabbits under semi-occlusive conditions for 4 hours.

All three rabbits showed severe erythema (grade 4, including moderate ischemic necrosis, moderate incrustation) and severe edema (grade 4). These effects were completely reversible within 21 days after treatment. Thus, the registration substance (20% a.i.) is irritating to the skin.

 

As the results were on the borderline to corrosive, a further in vitro test with the neat substance was performed.

The skin corrosion of the lyophilised registration substance (100%) was tested in a human skin model in vitro, according to EC method B.40 (2000/33/EC) and OECD guideline 431 (2002). The cells were treated with a dose of 25.0-27.0 mg wetted test item.

After treatment, the absorbance values for the negative control were above the required acceptability criterion of OD ≥ 0.8 for both intervals. The viability of the positive control met the acceptance criterion with ≤30% concerning the 3 minute treatment (29.6%) and the 1 hour interval (6.12%). These criteria validate the test system.

After treatment with the test substance, the relative absorbance values were decreased to 90.6% for the 3 minute treatment but not to <50%. After 1 hour treatment the relative absorbance values were reduced to 55.0% but not to <15%. Therefore, the test item was considered to be non-corrosive in this in vitro test.

 

At the time of the conduct of the test, a further confirmatory test in vivo was required, thus a dermal irritation study according to OECD guideline 404 was performed with the lyophilised registration substance (99.4% a.i.) in 3 New Zealand white rabbits. The application of the test item to the skin resulted in mild to severe and early-onset signs of irritation such as erythema, edema and scaling. These effects were reversible and were no longer evident in the two surviving animals 14 days after treatment, the end of the observation period for all animals. One animal was noted with dry skin from the 24- to the 72-hour reading as well as with deep necrosis (full thickness destruction of the skin tissue) at the 48- and 72-hour reading. Thereafter, it was sacrificed for ethical reasons. According to the requirements specified by Regulation (EC) No 1272/2008 and GHS-UN, Amines, N-C10-16-alkyltrimethylenedi-, reaction products with chloroacetic acid requires classification for skin corrosion/irritation with classification category 1C, signal word “danger” and the hazard phrase “H314: Causes severe skin burns and eye damage”.

 

Eye irritation

In accordance with REACH-Regulation (Annex VIII, 8.2.1, column 2) testing of eye irritating properties of the neat substance in vivo does not need to be conducted because the substance is already classified for irreversible effects on the eye based on the outcome of the in vivo skin irritation study ("Causes severe skin burns and eye damage").

However, an in vivo eye irritation study is available with the registration substance (20% aqueous solution) which constitutes the active substance as manufactured.

Diffuse beefy redness and swelling with lids about half closed or more than half closed as well as lesions of the iris grade 2 (no reaction to light, haemorrhage and/or gross destruction) were observed throughout the study period of the eye irritation study. Reversibility was not observed within the observation period of 72 hours. According to the guidelines, absence of the light reflex (iridial response grade 2) which persists for 72 hours is generally not reversible.Thus, according to the requirements specified by regulation (EC) No 1272/2008 and GHS-UN, the registration substance has to be classified in Category 1, irreversible effects on the eye.

A further study according to OECD TG 405 is available with a 1% aqueous solution of the registration substance. Reversible effects on the iris were observed 24 hours after treament (grade 1 in one animal). Conjunctival redness and chemosis were observed at the 24/48/72 h observation with the following grades for animals 1 to 3: redness: 2, 1.67 and 2, respectively and chemosis: 2, 2 and 1.67, respectively. The observation period lasted only 72 hours. However, it can be assumed that the effect are reversible because the grades of conjunctival redness and chemosis decreased over the observation time. Thus, according to the requirements specified by regulation (EC) No 1272/2008 and GHS-UN, the 1% aqueous solution of the registration substance has to be classified in Category 2A , reversible effects on the eye.

Respiratory irritation

There are currently no validated animal or in vitro tests that deal specifically with respiratory tract irritation. The Guidance on the Application of the CLP Criteria, Version 4.0, Nov. 2013 states that: "In general, a classification for corrosivity is considered to implicitly cover the potential to cause RTI [= respiratory tract irritation] and so the additional [STOT-SE] Category 3 is considered to be superfluous".

The classification of the substance as corrosive, Category 1C is considered to cover and communicate the potential for respiratory tract irritation adequately. 

Based on reliable, adequate and relevant data, the registration substance has to be classified in Category 1C according to CLP, EU GHS (Regulation (EC) No 1272/2008) and GHS-UN and is assigned the hazard statement H314 “Causes severe skin burns and eye damage”.

The technical material as manufactured is a liquid with ca. 20% w/w active ingredient and ca. 80% w/w water. A water-free form of the technical material (dry technical material) is not manufactured or sold for commercial purposes.

The 20% aqueous solution of the registration substance is classified as irritating to the skin (Category 2) and causing irreversible effects on the eye (Category 1) and labelled with H315 (Causes skin irritation) and H318 (Causes serious eye damage) according to regulation (EC) No 1272/2008 and GHS-UN. A 1% aqueous solution of the registration substance is causing reversible effects on the eye (Category 2A) and has to be labelled with H319 (Causes serious eye irritation) according to regulation (EC) No 1272/2008 and GHS-UN.