Registration Dossier

Administrative data

Description of key information

Skin irritation, in vitro, EpiDerm (according to OECD TG 439, GLP): no skin irritating potential of the test substance was found (BASF SE, 2011).
Serious eye damage, in vitro, BCOP (OECD TG 437, GLP): the test substance does not cause serious eye damage under the test conditions applied (BASF SE, 2011).
Eye irritation, in vitro, EpiOcular (no guideline available, GLP, Val. 1): no eye irritating potential of the test substance was found (BASF SE, 2011).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

- In vitro tests

The potential of the test substance to cause dermal corrosion/irritation was assessed by a single topical application of 30 μL of the test substance to a reconstructed three dimensional human epidermis model (EpiDerm™), according to the OECD TG 439 (BASF SE, 2011).

The irritation test was performed with 3 EpiDerm™ tissue samples, which were incubated with the test substance for 1 hour followed by a 42-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation in a colorimetric test, using the reduction of mitochondrial dehydrogenase activity (measured by reduced formazan production after incubation with a tetrazolium salt [MTT] in comparison to the negative control tissues) as endpoint. The quotient of the test substance and negative control values indicates the relative tissue viability.

Following results were obtained: (1) the test substance is not able to reduce MTT directly; (2) in the irritation test; the mean viability of the test-substance treated tissues was 113 ± 2% after 1 hour exposure and ca. 42 hours post-incubation.

This Test may be used for the hazard identification of irritant (OECD TG 439) chemicals in accordance with EU CLP Category 2. Based on the observed results and applying the evaluation criteria, the test substance does not show a skin irritation potential in the EpiDerm™ skin corrosion/irritation test under the test conditions chosen. Therefore, the test substance is not irritating according to EU CLP. Additionally taken into account that no irritation reaction was observed in the acute demal toxicity study conducted according to the OECD TG 402 in rats up to a dose level of 5000 mg/kg bw, the likelihood of a mildly irritating potential also can be excluded (the test substance is therefore not irritating according to GHS).

Eye irritation

- In vitro tests

In a first in vitro study conducted according to the OECD TG 437 (BASF SE, 2011), the potential of the test substance to cause serious damage to the eyes was assessed by a single topical application of 750μL of the test substance to the epithelial surface of isolated bovine corneas, for an exposure period of 1 hours (Val 1).

Corneal opacity was then measured quantitatively as the amount of light transmission through the cornea, as well as permeability as the amount of sodium fluorescein dye that passes across the full thickness of the cornea. Both measurements were further used to calculate an In Vitro Irritancy Score (IVIS = mean opacity value + 15 * mean permeability OD value) of the test substance relative to the control corneas. A risk of serious damage to the eyes is predicted if the IVIS per treatment group was greater than 55, and no risk of serious damage to the eyes was predicted otherwise (if the IVIS per treatment group is ≤55). The calculated mean IVIS was 1.5 ± 0.9, -0.2 ± 0.2, and 145.6 ± 7.8, respectively in the test substance group, the negative control group and the positive control group. Based on the observed results and applying the evaluation criteria, the test substance does not cause serious eye damage in the Bovine Corneal Opacity and Permeability Test (BCOP Test) under the test conditions chosen.

The potential of the test substance to cause eye irritation was further evaluated in a second study, also conducted following the testing strategy for determination of eye irritation/corrosion as given in the OECD TG 405 and using a three dimensional human cornea model, based on the observation that irritant chemicals produce cytotoxicity in human reconstructed cornea after a short term topical exposure (BASF SE, 2011). In the well conducted GLP study (Val 1), 50 μL of the test substance was applied to a reconstructed three dimensional human cornea model (EpiOcularTM; 2 tissue sample per treatment) and the treated tissue was incubated for 30 minutes, washed out, and post-incubated under normal medium and culture conditions for 2 hours. Tissue destruction was then determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. The test substance was considered "irritant", if the mean relative tissue viability with a test material is less than or equal to 50%, “non-irritant” or inconclusive otherwise.

The test substance was not able to reduce MTT directly, and the mean viability of the test-substance treated tissues was 83 ± 4%. Based on the observed results and applying the evaluation criteria, it was concluded, that the test substance does not show an eye irritation potential in the EpiOcular™ eye irritation test under the test conditions chosen.

 

Additionally read across from the structural analog 2,2`oxybisethanol, propoxylated (3 mol PO) for which a reliable in vivo eye irritation assay is available (OECD 405, reliability 1, BASF SE 2010) did not indicate any concern for an eye irritating potential.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data are considered reliable and suitable for the purpose of classification. Based on the criteria for classification of Directive 67/548/EEC no classification is warranted for skin and eye irritation.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification. No classification is warranted for skin and eye irritation.