Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Additional information

Skin irritation

The potential for tertiary butyl acetate to cause skin corrosion/irritation is well understood. In the key study, a dermal irritation study conducted according to EPA OTS Guideline 798.4470 in which tertiary butyl acetate was applied to intact skin sites in male and female rabbits under semi-occluded contact for 4 hours, no edema was noted in any of the animals, the mean erythema score was 0.66 at 24 hours, and irritation was fully reversible by the 48 hour observation period. In addition, when a dermal toxicity study conducted according to EPA OTS Guideline 798.1100 was performed in 5 albino rabbits/sex at a limit dose level of 2000 mg/kg bw, no signs of irritation, necrosis, ulceration or evidence of tissue destruction were observed at any time during the 14 day observation period following 24-hour occluded contact. Tertiary butyl acetate may cause minimal transient irritation to intact skin following prolonged contact.

  

Eye Irritation

The potential for tertiary butyl acetate to cause eye burns/irritation is well understood. In the key study, an eye irritation study conducted according to EPA OTS Guideline 798.4500, 0.1 mL of undiluted tertiary butyl acetate was instilled into the conjunctival sac of one eye of each of 6 male New Zealand albino rabbits. The treated eyes were examined and graded for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours after dosing. Corneal opacity (Grade 2) was limited to 1/6 eyes at the 24-hour observation only. Irritation of the iris (Grade 1) was observed in 3/6 eyes at the 1-hour observation and in 1/6 eyes at the 24-hour observation. Erythema (Grade 2), chemosis (Grade 2), and a discharge (Grade 2) were observed in all eyes at the 1-hour examination. Erythema (Grade 1 or 2) persisted for up to 48-hours while chemosis (Grade 2) and discharge (Grade 2) was limited to a single eye at 24-hours. All eyes were clinically normal at the 72-hour observation. Based on an absence of skin irritation and the rapid reversibility of effects noted in an eye irritation study in rabbits, tertiary butyl acetate may cause slight transient eye irritation.

  

Respiratory Tract Irritation

The potential for tertiary butyl acetate to cause respiratory tract irritation is well understood. In an acute inhalation study conducted to be in compliance with ECC, OECD, US-EPA and J-MAFF test guidelines, clinical signs suggestive of respiratory tract irritation, i.e., exaggerated, noisy, and /or slow breathing were observed in groups of male and female rats during or following exposure (nose only) to measured concentrations of 1873, 3502 and 5066 ppm tertiary butyl acetate for 6 hours. Gross observations at necropsy of animals that died prior to study termination included minimal to severe congested lungs. Treated animals that survived to study termination also exhibited minimal to moderate congestion of the lungs (one 3502 ppm group male) and dark foci on the lungs (one 1873 ppm and two 3502 ppm group males). Similar findings were not observed in control animals. In a second acute inhalation study conducted according to EPA OTS Guideline 798.1150 in which groups of male and female rats were exposed (nose only) to 470 ppm tertiary butyl acetate for 4 hours, no clinical signs suggestive of respiratory tract irritation were observed and no gross abnormalities were noted at necropsy.

  

In a non-guideline repeat exposure study in which groups of male and female rats were exposed (nose only) to up to 1600 ppm tertiary butyl acetate for 6 hours/day, 5 days a week for a total of 11 exposures, there were no unscheduled deaths and no clinical signs of respiratory tract irritation. No treatment-related gross or microscopic abnormalities were observed in the lungs at study termination. Inhalation exposures of mice to 100, 400 or 1600 ppm tertiary butyl acetate in repeated exposure studies caused labored respiration in a few males and females at the highest exposure level during exposure but not immediately following exposure. There were also isolated incidences of labored respiration at the two lower concentrations during the first three weeks of exposure.

  

The clinical signs observed in the acute and repeat-exposure inhalation studies along with congested lungs observed at necropsy in the acute inhalation study suggest that acute inhalation exposure to high concentrations of tertiary butyl acetate may be acutely irritating to the respiratory tract of laboratory animals.

Justification for classification or non-classification

In a dermal irritation study in which tertiary butyl acetate was applied under semi-occluded contact to intact rabbit skin for four hours, there was no evidence of edema, the mean erythema score was < 1 at the 24-hour observation period, and all animals were clinically normal by 48 hours. In a dermal toxicity study in which dose (2000 mg/kg bw) and length of exposure (24 hours) were significantly more severe than OECD guidelines for a skin irritation study, no signs of irritation, necrosis, ulceration or evidence of tissue destruction were observed at any time during the 14-day observation period. Based on a weight-of-the-evidence assessment, tertiary butyl acetate is not classified for skin irritation/corrosion according to EU CLP (Regulation (EC) No. 1272/2008) and UN GHS. In the EU Directive 67/548/EEC, tertiary butyl acetate had to carry the R66 risk phrase “Repeated exposure may cause skin dryness or cracking”. Annex VII to CLP Regulation (EC) No. 1272/2008 contains translation tables to translate risk phrases that were assigned under Directive 67/548/EEC into supplementary labeling requirements under CLP. The corresponding label statement under CLP Regulation (EC) No. 1272/2008 is EUH066 “Repeated exposure may cause skin dryness or cracking.”

Undiluted tertiary butyl acetate caused slight, transient eye irritation when a volume of 0.1 mL of the test material was placed in the eyes of six rabbits. No signs of systemic toxicity were observed. Initial signs including slight to moderate corneal opacity, iritis, chemosis, and/or discharge were absent by 48 hours. All animals were clinically normal by the 72-hour examination. Tertiary butyl acetate is not a skin irritant and is not classified for eye irritation according to EU CLP (Regulation (EC) No. 1272/2008) and UN GHS.

 

Based on clinical signs observed in acute and repeat-exposure inhalation studies along with congested lungs observed at necropsy in an acute inhalation study, tertiary butyl acetate may cause respiratory tract irritation. Therefore tertiary butyl acetate classification as Category 3 for Specific Target Organ Toxicity – Single Exposure according to EU CLP (Regulation (EC) No. 1272/2008) and UN GHS is warranted. A harmonized classification exists for tertiary butyl acetate; however, and this hazard category is not included. A recommendation is made to add STOT-SE Category 3, H-335 "May cause respiratory irritation" to Table 3.1 of Annex VI.