Registration Dossier

Administrative data

Description of key information

In vitro eye irritation, in vivo eye irritation and in vivo skin irritation studies were conducted on MTDID 15670. The results of the studies were:

 

Eye Irritation: Not irritating when tested according to OECD 405 (2012). 

Eye Irritation: No prediction can be made regarding eye irritation potential when tested according to OECD 437.

Skin Irritation: GHS Category 2 irritant when tested according to OECD 404 (1992).

Key value for chemical safety assessment

Additional information

Eye Irritation:

 

The primary ocular irritation/corrosion potential of the test material, MTDID 15670, was evaluated in three male New Zealand White rabbits. The study was based on OECD 405 (2012) and was certified GLP. The study was performed in a stepwise manner and was started by treatment of a single animal (sentinel) and the other two were treated in a similar manner 10 days later after considering the degree of eye irritation in the first animal. Approximately 96.2 mg (approximately 1 mL) unchanged test material was instilled to the conjunctival sac of one eye by gently pulling the lower eyelid away from the eye; the other eye of each animal served as a control. Eyes were held together gently for approximately one second to prevent loss of the test item. The treated eye of each animal was examined for irritation of the cornea, iris, and conjunctivae at 1, 24, 48 and 72 hours and/or 7 and 14 days post exposure. After the 24-hour observation, a solution of 2% fluorescein in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage; this was repeated to assess recovery. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol®. Additional observations for mortality/viability (twice daily), toxicity (at least once daily), and body weight (day 1 prior to exposure and after final observation) were recorded.  

 

Instillation of approximately 96 mg of MTDID 15670 (approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the cornea, iris and/or conjunctivae. Mean (24, 48, and 72 hours) corneal capacity scores for the three animals were 0.0, 0.0 and 0.7. Mean (24, 48, and 72 hours) iritis scores for the three animals were 0.0, 0.3 and 0.3. Mean (24, 48, and 72 hours) conjunctival redness scores for the three animals were 1.7, 0.7, and 1.7. Mean (24, 48, and 72 hours) conjunctival chemosis scores for the three animals were 0.3, 0.3 and 2.0. The irritation had completely resolved within 72 hours after instillation in one animal and within 14 days in the other two animals. Corneal injury and iridial irritation resolved within 72 hours. There was no evidence of ocular corrosion. Remnants of the test item were present on the outside of the eyelids on Day 1 in one animal. No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on the results of the study, the instillation of approximately 96 mg of MTDID 15670 was not irritating and not corrosive to the eyes of rabbits. 

 

The ocular irritation and corrosion potential of MTDID 15670 was tested in the Bovine Corneal Opacity Permeability (BCOP) test. The test method was based on OECD 437 and was performed in compliance with GLP. The eyes were examined prior to use on the day of dosing. Any eye with a cornea exhibiting evidence of vascularization, pigmentation, opacity or scratches was discarded. Corneas from eyes that were free of defects were dissected from the surrounding tissues. A 2-3 mm rim of sclera was left attached to each cornea. The corneas were then placed in a container of fresh HBSS. The dissected corneas were mounted in holders and placed in chambers filled with MEM solution. The entire holder was incubated at 32°C for at least 1 hour but not longer than 2 hours. Corneas (3/group) were treated with 0.75 mL undiluted test material, MTDID 51670, and incubated in the horizontal position for 10 minutes at 32°C. A positive control (100% ethanol) and negative control (MEM solution) were tested in parallel with the test material. At the end of the exposure period, the corneas were rinsed with a MEM solution containing phenol red; a final rinse was made with MEM without phenol red. After the final rinse, the corneas were incubated in fresh MEM solution for an additional 2 hours at 32°C. Opacity was evaluated using the OP-KIT following the 10-minute incubation and 2-hour post-exposure incubation. Following opacity readings, the cell culture medium was replaced with Na-fluorescein medium and incubated for approximately 90 minutes at 32°C. Following the 90-minute Na-fluorescein exposure, permeability was measured as the optical density at 490 nm by a spectrophotometer. The In Vitro Irritancy Score (IVIS) for the test material and positive control was calculated by adding the corrected mean opacity score to fifteen times the corrected mean optical density; the IVIS for negative control was performed by adding the mean opacity score to fifteen times the mean optical density. Based on the IVIS score, the test article was classified according to the prediction model described in DB-ALM Protocol No. 1271, a modification of the prediction model suggested by Gautheron, et al. (1994). The mean IVIS for MTDID 15670 was 3.95. The mean opacity score was 3.66 and the mean optical density score was 0.019. Controls performed as expected. Based on the IVIS score of 3.95, no prediction can be made regarding the eye irritation potential of MTDID 15670; according to GHS, no prediction can be made when the IVIS is >3 to </= 55. Data are insufficient for classification. An acute ocular irritation study has been performed to establish the ocular irritation potential. 

 

Skin Irritation:

 

The dermal irritation potential of MTDID 15670 (unknown form, lot unknown) was evaluated in rabbits. The study design was based on the recommendations in US CFR Title 16, Section 1500.41. Six hair clipped rabbits received test material on one abraded and one intact test site. The test material was held in place with 1 inch x 1 inch gauze, adhesive tape, and an impervious material such as rubberized cloth was wrapped around the torso of the rabbit. After 24 hours of exposure the patches were removed and the sites were scored for erythema and edema (0-4 scales). Observations are recorded at 24 and 72 hours after the exposure period and the scores of all sites are averaged together to produce the primary dermal irritation index (PDII) . Animals were not observed beyond 72 hours after exposure. Erythema (scores: 2-3) and edema (scores: 1-3) were observed at all treated sites at both observation times. Blanching of the skin was observed in intact sites (4 animals) and abraded sites (5 animals) at 24 hours post-exposure. Blanching and cracked skin was observed in 3 animals at 72 hours post-exposure. The PDII was 5.0. Based on the results of this study, MTDID 15670 is a moderate skin irritant.

Justification for classification or non-classification

Based on the results of the studies, the test article not classified for eye irritation and is a Category 2 dermal irritant according to GHS.