1-Butanamine, N-[3-(trimethoxysilyl)propyl]-, reaction products with (trimethoxysilyl)-N-[(trimethoxysilyl)propyl]-1-propanamine and 1,6-diisocyanatohexane homopolymer

Endpoint summary

Description of key information

OECD 404 (Bioassay, 2013): not irritating to the skin
OECD 405 (Bioassay, 2013): not irritating to the eye

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)

Additional information

Skin irritation in vivo:

The potential of iGloss Crosslinker (ZQ54-2211) to cause acute dermal irritation or corrosion was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The study was conducted according to OECD 404 guideline and GLP (Bioassay, 2013).

The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and in weekly intervals until day 14 at the latest.

The following test item-related clinical observations were recorded during the course of the study:

- Very slight erythema (grade 1)

- Scaling

The cutaneous reactions, with the exception of scaling, were reversible in one animal within 14 days after removal of the patch. In one animal cutaneous reactions were reversible within 72 hours and in one animal within 7 days after removal of the patch. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.7 and 0.7 for erythema and 0.0, 0.0 and 0.0 for edema.

Considering the described cutaneous reactions as well as the average score for irritation, iGloss Crosslinker (ZQ54-2211) does not show a skin irritating potential under the test conditions chosen.

Skin irritation/corrosion in vitro:

The potential of the test item to induce skin irritation was assessed according to OECD431/439 and GLP in an in vitro human epidermis skin model. The corrosion test involved application of 50 µl of the test item for 3 min or 1 h, respectively to two skin samples. Immediately after incubation, the viability of the human epidermis was assessed by MTT assay; the negative control was set at 100% cell viability. Since the viability was 93% after 3 min and 95% after 1 h, the test substance is not corrosive. To identify a irritating potential of the test item, 30 µl of the undiluted test item were applied to three epidermis samples and incubated for 1 hr at 37°C. Following removal of the test item, the tissue samples were incubated for 48 h at 37°C, before cell viability was measured by MTT assay. Cell viability was 77% in the treated samples, indicating that the test item does not possess a skin irritating potential. Based on the observed results and applying the evaluation criteria cited above it was concluded that iGloss Crosslinker (ZQ54-2211) does not show a skin irritation potential in the EpiDerm™ skin corrosion/irritation test under the test conditions chosen.

Eye irritation in vivo:

The potential of iGloss Crosslinker (ZQ54 -2211) to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL of the test item to one eye of three White New Zealand rabbits (stepwise procedure starting with one animal and supplementing two additional animals). The study was conducted according to OECD 405 guideline and GLP (Bioassay, 2013). About 24 hours after application the eye was rinsed with tap water.

The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application.

The following test item-related clinical observations were recorded during the course of the study:

- Slight and obvious conjunctival redness (grade 1-2)

- Slight conjunctival chemosis (grade 1)

- Slight or obvious discharge (grade 1-2).

- Additional findings like injected scleral vessels in a circumscribed area at hour 1 or hair loss from hour 24 until hour 72.

The ocular reactions were reversible in all animals within 48 or 72 hours after application, respectively.

Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity, 0.0, 0.0 and 0.0 for iris lesions, 0.7, 0.7 and 0.3 for redness of the conjunctiva and 0.0, 0.0 and 0.0 for chemosis.

 

Considering the described ocular reactions as well as the average score for irritation, iGloss Crosslinker (ZQ54-2211)does not show an eye irritating potential under the test conditions chosen.

Eye irritation (EpiOcular):

The potential of the test item to induce eye irritation was assessed by means of an in vitro EpiOcular assay. 50 μL of the test substance was applied topically to a reconstructed three dimensional human cornea model (EpiOcular™). Two EpiOcular™ tissue samples were incubated with the test substance for 30 minutes followed by a 2-hours post-incubation period. Water was used as negative control and methyl acetate as positive control.

Tissue destruction was 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 testsubstance treated epidermal tissues is compared to that of negative control tissues. The quotient of the values indicates the relative tissue viability. Using this assay, the mean viability of the test-substance treated tissues was 96%, indicating that the test item does not have the potential to irritate the eyes.

Eye corrosion (BCOP):

The potential of the test item to cause serious damage to the eyes was assessed in an in vitro bovine cornea opacity and permeability (BCOP) test according to OECD guideline 437 and GLP. Three isolated cornea from freshly slaughtered cattle were prepared per treatment group (positive control (PC), negative control (NC) and test item); 750 μL of the undiluted liquid test substance was applied directly to the epithelial surface of the cornea using a pipette (open chamber method). Control tissues were concurrently applied into the anterior chamber with 750 μL of de-ionized water (NC) or with 750 μL of 1% (w/v) solution of sodium hydroxide in deionized water (PC) using a pipette. The corneas were incubated in a horizontal position at about 32 °C for approximately 10 minutes (liquids and surfactants) and the test item or controls removed thereafter. The corneas were incubated for further 2 hours at about 32 °C. After the incubation period the medium was removed and both chambers were then refilled with fresh Eagle’s MEM.

Corneal opacity was subsequently measured with an opacitometer; for determination of permeability the medium in the anterior chamber was replaced by 1 mL sodium fluorescein solution (4 mg/mL for liquid test substances and surfactants) and incubated for 90 ± 5 min in a horizontal position at about 32 °C. The amount of sodium fluorescein that permeated through the corneas into the posterior chamber was measured spectrophotometrically. Three aliquots per cornea were transferred to a 96-well microtiter plate and the optical density (OD490) was determined.

The mean corneal opacity and permeability values of each treatment group were used to calculate an In Vitro Irritancy Score (IVIS). The positive and negative controls were within the hisorical control, indicating reproducibility and robustness of the test method. The calculated IVIS value is -1.5 and therefore below the threshold value of 55, it can be concluded that the test item does not cause any serious damage to the eyes.

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to skin and eye irritation according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.