2-ethylhexanal

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

Short description of key information:
No data available.

Effects on developmental toxicity

Description of key information

NOAEL: developmental toxicity:  300.9 mg/kg bw/day 
NOAEL: maternal toxicity: 300.9 mg/kg bw/day 

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

300.9 mg/kg bw/day

Additional information

Developmental toxicity of 2-ethylhexanal was assessed according to OECD guideline 414 Huntingdon 1999; Val 1). 2-ethylhexanal was administered by daily oral gavage to rats from day 6 to 19 of their pregnancy, at dosages up to 797.6 mg/kg bw/day. There was no obvious adverse maternal toxicity at 100.0 or 300.9 mg/kg bw/ day. In contrast, at 797.6 mg/kg bw/day there was clear evidence of maternal toxicity (piloerection and underactivity, eyelids partly closed and hunched posture; low food consumption and reduction of overall absolute and adjusted bodyweight gain). Embryo-fetal survival was unaffected by treatment with 2-Ethylhexanal.

At 300.9 mg/kg bw/day, fetal weights were lower and there was delayed ossification. The relationship of these findings to treatment is uncertain. Beyond this, they are considered to be transient in nature, rather than representing permanent structural changes. Therefore the slight fluctuations in fetal weights and some ossification parameters are not considered to be of toxicological relevance during later development. According to the authors other effects observed at 300.9 mg/kg are either with in the range of the historical control (rudimentary/ absent renal papillae; dilated ureter) or marginal and not dose related (displaced testes) or only slightly increased but possible artefacts (haemorrhages of brain/spinal cord). Therefore these effects were considered not to be substance related and of no toxicological relevance.

At 797.6 mg/kg bw/day fetal and placental weights were reduced and placental abnormalities were observed in a few litters, e.g. pale placenta (3 litters; about 10% of the placenta overall). Fetal pathology revealed visceral and skeletal abnormalities at 797.6 mg/kg bw/day (visceral: dilated brain ventricles, absent/rudimentary thyroid gland, cardiovascular abnormalities and rudimentary/absent renal papillae; skeleton: reduction in ossification, rib and vertebral abnormalities and changes in configuration not related to fetal immaturity). Fetal immaturity was noted universally at 797.6 mg/kg bw/day and, to a lesser extent, at 300.9 mg/kg bw/day.

In conclusion, there was no evidence of adverse maternal or embryo-fetal toxicity at 100.0 mg/kg bw/day. Similarly, at 300.9 mg/kg bw/day no obvious adverse maternal toxicity was seen but there was some delayed ossification. Effect is considered to be transient in nature, rather than representing permanent structural changes and of no toxicological relevance during later development . At 797.6 mg/kg bw/day, maternal toxicity was clearly evident and 2 -ethylhexanal is toxic to the developing embryo and fetus. The NOAEL for both, maternal toxicity and developmental toxicity is considered to be 300.9 mg/kg bw/day.

Justification for classification or non-classification

Based on the available data and according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, 2 -ethylhexanal is classified with R63 (possible risk of harm to the unborn child) and H361d (suspected of damaging the unborn child).