Butyraldehyde

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route

Dose descriptor:

NOAEC

3 560 mg/m³

Additional information

In the study conducted by Driscoll (1993), 15 male and female CD rats were exposed to the test substance, Propionaldehyde, by whole-body exposure at air concentrations of 0, 150, 750 and 1500ppm.Exposures were conducted 6‑hours per day, 7‑days per week. Males received 52 consecutive daily exposures, while females were exposed for 2 weeks prior to mating, during a 14-day (Maximum) mating period and through day 20 of gestation.On day 4 of lactation, necropsies were performed on the adult females and the offspring were examined externally and sacrificed without pathologic evaluation. Following repeated whole-body exposure to the test substance at the aforementioned concentrations, there was minimal toxicity at the two highest concentrations in females; males showed no apparent toxicity. Microscopic examination of the nasal epithelium revealed treatment-related effects at all concentrations in both parental sexes. No significant effects of exposure were noted on any reproductive parameter assessed. Litter size and viability were similar among exposed and control groups. Pup body weights on postnatal day 0 and 4 were not affected by exposure, however, a slight decrease in body weight gain was observed in the 1500 ppm offspring.  The LOAEC for parental toxicity is 150 ppm, based on the presence of nasal lesions at 150 ppm, the lowest concentration tested.The NOAEC for reproductive toxicity is 1500 ppm (3560 mg/m3) and the NOAEC for pup toxicity, based on a slight decrease in body weight gain in pups at day 4, is 750 ppm.

In the study conducted by Morrissey et al (1988), rats and mice were exposed to the test substance, isobutyraldehyde, at concentrations of0, 500, 1000, 2000, or 4000 ppm and0, 500, 1000, or 2000 ppm, respectively. The test animals were exposed to the test substance via inhalation of vapours for a period of 13 weeks. Decreased body weight, decreased absolute but not relative weight of right cauda epididymis, and decreased absolute and relative weight of right epididymis with no significant weight change of the right testis of rats exposed to vapor concentrations up to 4000 ppm. No effects were noted on sperm motility, sperm density or increases in sperm abnormalities. No weight change of reproductive organs or effects on sperm were noted in male mice exposed to vapor concentrations up to 2000 ppm isobutyraldehyde for 13‑weeks (5890 mg/m3). Based on the results of this study, there were no adverse effects noted on the reproductive parameters of the mice and rats examined and as such, the test substance does not require classification.

Short description of key information:
There are 2 reproductive toxicity studies available for the structurally-related read-across substances propionaldehyde and isobutyraldehyde. The read-across substances are both simple short-chain aldehydes; propionaldehyde differs from n-butanal (butyraldehyde) only in the length of carbon chain, while isobutyraldehyde is a structural isomer. Read-across is justified as the toxicity of the substances can be predicted to be due to the common reactive aldehyde group. The studies all used either rats or mice as the test species, with strains including CD and Fischer 344 rats while the strain of mouse used was B6C3F1. The test guidelines followed included EPA OPP 83-3 (Prenatal Developmental Toxicity Study).

Effects on developmental toxicity

Description of key information

There is one developmental/teratogenicity study available for the structurally-related read-across substance, isobutyraldehyde. The study used Wistar rats as the test species and the study followed OECD Guideline 412.

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

12 mg/m³

Additional information

Garner et al. (1996) examined the potential of isobutyraldehyde to induce reproductive toxic effects when tested in groups of 25 mated female Wistar rats exposed to the test substance 6 hours per day on days 6 through15 of gestation. The test animals were exposed to the test substance at concentrations of 1000, 2500 and 4000ppm. The results of this study indicate a dose-related increase in maternal toxicity but exposure of the dams to isobutyraldehyde had no effect on gestational or litter parameters and did not induce embryo/foetal toxicity. There was no increase in foetal malformations at any exposure level, up to the highest concentration tested. Based on the results of this study, it can be concluded that the test substance, isobutyraldehyde, did not induce any reproductive toxicity when tested in female mated Wistar rats.

Justification for classification or non-classification

The results of the available studies do not show any evidence of specific reproductive toxicity for the structurally-related read-across substances propionaldehyde and isobutyraldehyde. A developmental toxicity study with isobutyraldehyde did not show any evidence of developmental toxicity. No classification is therefore proposed for reproductive toxicity according to Directive 67/548/EEC or Regulation 1272/2008/EC (CLP).