Allyl alcohol

Endpoint summary

Description of key information

A total of five studies have been identified as having assessed the repeat-dose toxicity of allyl alcohol; three key studies and a supporting study have been identified for the oral route and one key study has been identified for inhalation exposure. The three key studies identified for the oral route followed methods comparable to OECD guideline 408: two were performed under GLP and the third tested the major metabolite of allyl alcohol, acrolein. The inhalation route key study followed a method that is equivalent to OECD guideline 413, but was not performed under GLP.  The repeat dose lethality in the inhalation study, suggests that allyl alcohol should be considered to pose a toxicological hazard upon repeated exposure to moderate concentrations.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

3 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

47.5 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

Repeated dose oral toxicity:

In the key subchronic oral toxicity study with rats, allyl alcohol was administered in aqueous 0.5% methylcellulose to groups of 10 male and female rats (Wistar) at dose levels of 0, 1.5, 3, 6, 12, or 25mg/kg bw. In the 6, 12 and 25 mg/kg groups, there was a significant increase in relative liver weights and significant increases in the incidence of squamous epithelial hyperplasia in the forestomach. Females of the 25 mg/kg group also showed high incidences of bile duct hyperplasia and liver periportal hypertrophy. The oestrus cycle also appeared to be affected in the 25 mg/kg female group where the diestrus period was prolonged and metestrus period was reduced in comparison to the vehicle controls. Based on these findings the NOAEL is 3 mg/kg/day and the LOAEL 6 mg/kg/day.

In the key subchronic toxicity study with mice (allyl alcohol administered to 10 male and female mice per group at 0, 3, 6, 12, 25 or 50 mg/kgbw/day), the NOAEL was 6 mg/kg/day and the LOAEL 12 mg/kg/day.

The key chronic repeated-dose rat study was performed with the allyl alcohol metabolite acrolein and hence its NOAEL and LOAEL values are not directly applicable to allyl alcohol.

Repeated dose dermal toxicity: available data on acute oral and dermal toxicity suggest that allyl alcohol is well absorbed via the skin. No repeat-dose dermal studies have been located, but the available repeat-dose toxicity data for oral and inhalation routes is considered sufficient to define a toxicity profile which will be of relevance to long-term dermal exposure.

Repeat dose inhalation toxicity:

In a subchronic inhalation toxicity study allyl alcohol vapour was administered to 10 male rats per group (Long-Evans strain), by whole body exposure at concentrations of 0, 1, 5, 20, 40, 60, 100 and 150 ppm for 7 hours per day, 5 days/week for 12 weeks (except at 100 and 150 ppm, where limited by mortality). 150 ppm proved 100% lethal (within 10 exposures) and at 100 ppm 6/10 rats died within 46 exposures. One animal died after 4 days exposure to 60 ppm. Clinical signs were absent in animals exposed to 20 ppm and below. Relative kidney weights increased by 8-10% in animals exposed to 40 ppm or 60 ppm; relative lung weight was increased after exposure to 40 ppm. Relative liver weights for treated animals were indistinguishable from those of the controls. Livers from rats in the 150 ppm allyl alcohol group appeared haemorrhagic and lungs were pale and spotted. The kidneys appeared normal. At the 150 ppm dose group microscopic examination revealed slight congestion of the lungs and liver. The LOAEC was 40 ppm, based on increased lung weight and clear retardation of weight gain.  The NOAEC is 20 ppm (47.5 mg/cu.m) .

 

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; digestive: stomach

Repeated dose toxicity: inhalation - systemic effects (target organ) digestive: liver; respiratory: lung

Justification for classification or non-classification

In addition to primary irritation effects in the forestomach, hepatotoxicity was evident in rats dosed orally at 25 mg/kg/day. These findings warrant classification as Xn, R48 according to Directive 67/548/EEC criteria and STOT RE Category 2 according to CLP (Regulation 1272/2008) and UN GHS criteria. No classification for these endpoints is given in the CLP Regulation Annex VI entry for allyl alcohol.