Registration Dossier

Administrative data

Description of key information

No in vitro assessments for skin or eye irritation available.  The in vivo data are limited but give no indication of irritation potential to either skin or eyes.

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

The RIFM Mongraph for hexyl acetate summarises the skin irritation study, providing a few more details than the 1973 publication (based on the information from previous publications in the series by Smyth et al).

 Primary skin irritation of the test material was assessed using 5 albino rabbits, by a single unoccluded application of undiluted test material to the clipped belly skin. In some instances, the test material was diluted as a solution in water, propylene glycol or acetone. The volume applied was 0.01 ml. Reactions were graded within 24 hours of the application, using a 1 - 10 scale (grade 1 = no irritation; grade 2 = least visible capillary injection from the undiluted material; grade 6 = necrosis from the undiluted material; and grade 10 = necrosis from a 0.01% solution).  Unless otherwise indicated, the results reflect the use of the undiluted test material.

Based on this information it appears that irritant reactions were observed but no adverse irreversible reactions such as necrosis occurred.

Read-across data from benzyl acetate confrm the severity of irritaton observed following dermal application to rabbits to be low and less than EU classification thesholds.

Eye irritation was evaluated using 5 albino rabbits per dose. The test material was applied to the center of the cornea while the lids are retracted, and approximately 1 minute later, the lids are released. The eye was examined in strong diffuse daylight 18 - 24 hours later, stained with fluorescein, and the injury scored. The vehicle was propylene glycol, water or Deobase. Eye injury was graded according to the following 10-point scale: 1 = 0.5 ml undiluted gives injury of 0 to 1 points; 2 = 0.5 ml undiluted gives injury of over 1 up to 5 points; 3 = 0.1 ml undiluted gives injury of up to 5 points (0.5 ml gives over 5); 4 = 0.02 ml undiluted gives injury of up to 5 points (0.1 ml gives over 5); 5 = 0.005 ml undiluted gives injury of up to 5 points (0.02 ml gives over 5); 6 = Excess of 40% solution gives injury of up to 5 points (0.005 ml gives over 5); 7 = Excess of 15% solution gives injury of up to 5 points (40% gives over 5); 8 = Excess of 5% solution gives injury of up to 5 points (15% gives over 5); 9 = Excess of 1% solution gives injury of up to 5 points (5% gives over 5); 10 = Excess of 1% solution gives injury of over 5 points. The points were equivalent to the following symptoms visible after fluorescein staining: 1 point = necrosis on less than 5% of the cornea; 2 points = necrosis on 5 12%; 3 points = necrosis on 13 37%; 4 points = necrosis on 38 - 62%; 5 points = necrosis on 63 - 87%; and 6 points = 88 - 100%. Grade 1 indicates a very small area of necrosis from 0.5 ml of undiluted material; grade 5 indicates a so-called severe burn from 0.005 ml; and grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.

Based on the results of the screening assay for ocular irritation in five rabbits, undiluted hexyl acetate did not elicit adverse ocular reactions indicative of irritation.

Read-across to a guideline compliant eye study for benzyl acetate, confirmed the low level of ocular effects and the absence of adverse effects in rabbits eyes that would require classification


Justification for selection of skin irritation / corrosion endpoint:
Read across data from benzyl acetate provides key indication of some irritation potential but generally only slight effects observed. This was supported by limited information available from an older non-guideline study. In vivo results confirm absence of any adverse dermal findings in either dermal irritation or dermal toxicity studies.

Justification for selection of eye irritation endpoint:
Limited information available but in vivo results confirm absence of any adverse findings. The key study is used for read across, supported by one unreliable study for hexyl acetate, both studies tend to show a low ocular hazard for exposure to these similar substances.

Justification for classification or non-classification

The indications from in vivo data demonstrate no potential for skin or eye irritation and consequently no classification is warranted for irritation in accordance with the criteria of the Dangerous Substances Directive or those of the Classification, Labelling and Packaging Regulation (EU) No 1272/2008, 3rd ATP.