Registration Dossier

Administrative data

Description of key information

The results of a modern, guideline-compliant dermal irritation study show that the substance is a slight skin irritant and does not require classification as a skin irritant. The results of a modern, guideline-compliant eye irritation study show that the substance requires classification as an eye irritant.

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:
adverse effect observed (irritating)

Additional information

Skin Irritation:

In a valid standard guideline study conducted by Kreiling R and Jung R (1988) using 3 rabbits according to OECD 404 and EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion), semiocclusive exposure of 4 h to undiluted butyraldehyde (0.5 ml) produced slight skin irritation: One through 72 hours after removal of the cover, barely perceptible (score 1) to distinct erythemas (score 2) were observed in all animals with a slight oedema in one animal after 24 h (score 1). All these effects subsided within 1 d in 1/3 animals and within 7 d in 2/3 animals, while the treated skin sites was still slightly scaly at this time.

In a study conducted by Union Carbide Corporation (1977), the test substance, butyraldehyde, was tested on 6 New Zealand White rabbits to determine its ability to induce skin irritation. The results of this study indicate that the test substance is not corrosive.

A study by Auletta (1981), was conducted to evaluate the primary dermal irritation produced by the test material C-243. The study was performed according to the guideline EPA 40 CFR Part 163.81 -5. The test material was applied to intact and abraded skin of 6 New Zealand White Albino rabits (3 per sex) for a period of 24 hours. The animals were observed for signs of erythema and oedema or other signs of irritation or injury 30 minutes after removal of the occlusive wrapping for a period fo 14 days. All animals exhibited necrosis at one or more sites at 24 and 72 hours. Eschar formation occurred subsequently at these sites and tissue destruction remained evident at termination of the study on day 14. Based on the results of this study, the test substance can be considered to be corrosive.

In the study conducted by Marhold (1972), 500 mg of butyraldehyde was applied to rabbits for a 24 hour exposure period. The application of the test substance resulted in severe skin irritation and as a result, the test substance was considered to be moderately irritating.

The study conducted by Kreiling R and Jung R (1988) was considered to be the key study as it satisfied the requirements of the relevant Guidelines and was considered to be reliable.

Eye Irritation:

In a valid standard guideline study conducted by Kreiling R and Jung R (1988), using 3 rabbits according to OECD 405 and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion), instillation of a single dose of undiluted butyraldehyde (0.1 ml) produced slight to moderate irritation which completely reversed within 48 hours to 7 days: One through 72 hours p.a., conjunctivae were distinctly hyperaemic (score 3 and 2), associated with slight to moderate swelling (score3, 2, 1). In 2/3 animals, the iris was transiently reddened (score 1 and 0), and the cornea transiently diffusely turbid (scores 1 and 0). Additionally, initially a clear, later a white slimy discharge and bleeding of the conjunctivae and nictitating membranes was observed. All effects completely subsided within 7 days.

In a valid standard guideline study conducted by Auletta (1981) (described under 40 CFR Part 163.81 -4), undiluted butyraldehyde (0.1 ml) produced severe irritation and injury to all eye parts observed in all treated animals. The recovery period for conjunctival tissue lesions was greater than 7 days for most rabbits. Eye washing after 20 sec after dosing failed to reduce irritating effects or responses to a significant extent. The detailed documentation of the observations and individual grading allows to evaluate the data in terms of current criteria.

In the study conducted by Union Carbide Corporation (1977), serial single instillations of diluted or undiluted test substance (Butyraldehyde) were placed in the conjunctival sac of 5 rabbits. The eyes were read immediately without fluorescein staining and then after fluorescein staining at 24 hours. The results of this study indicate severe corneal injury with iritis when applied at 0.02ml per eye. Moderate corneal injury occurred when 0.005ml test substance was applied to the eye. Based on these results and under the test conditions, the test substance can be considered to be highly irritating or corrosive.

In the study conducted by Smyth et al (1951), the test substance butyraldehyde was assessed for its ability to be an eye irritant. The results of this study indicate it is a Grade 8 eye irritant and as such, should be considered to be corrosive to the eye.

In the study conducted by Marhold (1972), the test substance, butyraldehyde, 20mg was applied to the eyes of rabbits. The rabbits were exposed to the test substance for 24 hours. Based on the results of this study, the test substance butyraldehyde was considered to be a moderate eye irritant.

The key studies were considered to be the study conducted by Kreiling R and Jung R (1988) and by Auletta (1981) as they were considered to be methodologically strongest and adhered to the relevant Guidelines. The remaining studies, adhered for the most part to the relevant guidelines, however, some methodological deficiencies meant their validity/reliability was questionable and as a result, they were considered to be supporting studies.


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin Irritation:

The results of the available studies are conflicting, however the majority of studies used non-standard exposure periods (24 hours) and/or abraded skin and are therefore considered to be less reliable and unsuitable as the basis for classification. The results of a modern, guideline-compliant dermal irritation study show that the substance is a slight skin irritant but does not require classification as a skin irritant according to Directive 67/548/EEC or Regulation 1272/2008/EC (CLP).

Eye Irritation:

The results of a number of eye irritation studies are consistent in demonstrating that the substance is an eye irritant, with varying degrees of irritation seen. The results of two modern, guideline-compliant eye irritation studies show that the substance requires classification as an eye irritant category 2 under Regulation 1272/2008/EC (CLP).