2-ethylhexanal

Endpoint summary

Description of key information

Repeated dose toxicity: 
oral: no valid data available
dermal: no data available
inhalation: NOAEC: 0.54 mg/L air for systemic toxicity; NOEC: 0.14 mg/L air for peroxisome proliferation

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

540 mg/m³

Additional information

Oral:

No valid data for the evaluation of the oral repeated dose toxicity available.

 

Dermal:

No valid data for the evaluation of the dermal repeated dose toxicity available.

 

Inhalation:

An inhalation repeated dose study was performed according to OECD TG 412 (BIBRA, 1997; Val. 2). Animals were exposed to 0.134, 0.536 and 1.34 mg/L air for 6 h/day on 5 days/week for 28 days. Treatment-related clinical findings were limited to transient porphyrin accumulation in the eyes in the high dose group. In the high dose group reduced body weights were observed in females on days 17 and 28, and in males of the same group over the duration of the study. A decreased percentage of lymphocytes and an increased percentage of neutrophils were observed in males and females in the high dose group. The clinical chemistry examinations of serum revealed decreased levels of fasting glucose and plasma cholesterol and increased levels of triglycerides in rats of the high dose group. Plasma alkaline phosphatase activity was increased in all treated groups. Gross examination at necropsy did not reveal any changes attributable to 2-ethylhexanal. Animals in the high dose group showed decreased thymus weight and increased weight of testes, heart (males), liver and lungs. The adrenal gland weights were increased in high dose males, and showed a dose-dependent increase in all treated groups of females. The mid- and high-dose groups of females showed dose-related increases in kidney weights, and this was also seen in males of the high dose group.

Electron microscopic and biochemical investigations were also conducted to investigate the induction of peroxisome proliferation in the rat liver. Although 2-ethylhexanal appeared to have the potential to induce small changes in peroxisomal and microsomal fatty acid oxidizing enzymes in the liver, the effects are much less marked than those produced by di(2- ethylhexyl)phthalate (DEHP, the concurrent positive control).

 

Justification for classification or non-classification

No classification according to repeated dose toxicity studies.

A NOAEC for overall effects/systemic toxicity of 102.2 ppm/0.54 mg/L air can be derived. The exposure of rats to 2-ethylhexanal produced small effects on relative liver weight at 25.5 ppm/0.14 mg/L air and on the markers of hepatic peroxisome proliferation measured, this dose can be used as a NOEC for peroxisome proliferation.