Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
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
Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Based on the results from the in vivo irritation studies, the  test substance is considered to be corrosive to skin as well as eyes.
Endpoint conclusion:
adverse effect observed (corrosive)
Endpoint conclusion:
adverse effect observed (irreversible damage)
Endpoint conclusion:
no study available

Skin

Study 1: A study was conducted to determine dermal irritation potential of the read across substance, C16-18 and C18-unsatd. TMAC (50% active in aqueous/isopropanol solution), in rabbits, according to a method similar to OECD Guideline 404. In the study, six rabbits (both sexes) were treated with 0.5 mL of undiluted read across substance 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 d 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 with an average irritation score was 5.4/8. After 10 d, 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 d. Under the test conditions, the undiluted read across substance was concluded to be non-corrosive after 1 h of occlusive exposure, but corrosive after 4 h of occlusive exposure (van Beek, 1982). Based on the results of the read across study, similar corrosion potential can be expected for the test substance.

Study 2:

A study was conducted to assess the skin irritation potential of undiluted C16 TMAC (purity not specified) on rabbit skin. Rabbits were prepared by clipping the skin free of hair. Four test application sites, approximately 25 x 25 mm, were delineated on the upper left, lower left, upper right and lower right flanks of the animal. 0.5 mL undiluted test substance was deposited into a 25 mm Hilltop Chamber and placed on each site. The entire area was then wrapped with tape. Patches were removed after 24 h of exposure. Skin sites were evaluated at 24 and 72 h after initial exposure and scored according to the method of 16 CFR 1500.41. The test substance was considered to be an irritant with a high erythema and oedema scores along with thickening of skin, black staining and brown discoloration observed after 72 h and a mean primary dermal irritation index (PDII) of 5.42 (Shapiro, 1990).

Eyes

Study 1:

A study was performed to assess the potential of C16 TMAC (5% active in water) to cause eye irritation in rabbit eyes, according to the Federal guideline: 16 CFR 1500.42.. 0.1 mL of undiluted test substance was placed in the conjunctival sac of the right or left eye of six rabbits. The other eye of each rabbit remained untreated and served as a control. After instillation of the test substance, ocular lesions were evaluated at 24, 48 and 72 h according to the Draize method. The eye irritation scores were further classified by the modified method of Kay and Calandra.All treated eyes had corneal opacity, iritis and conjunctival irritation during the 24-72 h test period.Apart from the eye irritation response, there were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. The 24 h maximum mean total score (MMTS) was 53. Based on the scoring system used, the test substance was considered to be extremely irritating (Shapiro, 1990).

Study 2:

A study was performed to assess the eye irritation potential of C16 TMAC (2% active in water) in rabbits, according to OECD Guideline 405, in compliance with GLP. 0.1 mL of the test substance (diluted at 2%) was placed in the conjunctival sac of the right eye of four rabbits. The other eye of each rabbit remained untreated and served as a control. Ocular lesions were evaluated at 1, 6, 24, 48, 72 and 96 h as well 8, 11 and 14 days post-application according to the Draize (1959) method. In two rabbits, a slight corneal reaction was observed 2 days after the start of the study but there were no effects on the iris in any of the animals. Moderate to severe effects were however noted on the conjunctiva of the rabbits, with full recovery at 11 days. Under the study conditions and based on the scoring system used, the test substance (2% dilution) was considered to be highly irritating to the eyes.

In the above two studies, eye irritation responses at concentrations up to 5% a.i. were moderate, and at 2% a.i., were reversible (Kästner, 1986). Data available on other TMAC substances tested at higher concentrations of active ingredient were found to have corrosive effects, suggesting that solutions containing a higher concentration of C16 TMAC may also be corrosive. This is consistent with the observed corrosive effects on the skin.


Based on the results of the in vivo skin and eye irritation studies, the test substance warrants a 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 C16 TMAC 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 and therefore an additional Cat.3 is considered to be superfluous (Guidance CLP Ch. 3.8.2.5). 

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion