Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

No reproductive toxicity study with EUF has been performed. The substance gave no indication for adverse effects on the reproductive organs in the subchronic gavage studies in rats. Data on formaldehyde suggested that this hydrolysis product does not reach the reproductive organs and there is no evidence for effects on fertility in experimental animals after oral or inhalation exposure. In oral fertility studies, ethylene glycol did not influence fertility parameters in rats and mice, but in male mice effects on reproductive organs were noted with a NOAEL below 897 mg/kg bw/day. No effects, however, can be expected at the more relevant dermal or inhalation routes of exposure.

No evidence for an impairment of fertility parameters was noted for urea.

Short description of key information:
A two-generation reproduction study with EUF has not been performed. Instead, a waiver was submitted.

Effects on developmental toxicity

Description of key information
Oral administration of EUF in a prenatal developmental toxicity study influenced fetal development at a moderate to severe maternal toxic dose. No teratogenic effect was observed.
Effect on developmental toxicity: via oral route
Dose descriptor:
110 mg/kg bw/day
Additional information

Developmental toxicity of EUF or formaldehyde is only expected secondary to local maternal effects.

EUF administered orally during the major phase of organogenesis to pregnant Himalayan rabbits resulted in no indication for teratogenicity, but influenced fetal development at a moderate to severe maternal toxic dose. Mean fetal body weights were statistically significantly reduced. Furthermore, a statistically significantly higher incidence of supernumerary ribs was noted. The increased incidence of supernumerary ribs in the fetuses might be secondary to the occurrence of maternal toxicity and are considered as variations of development. Rudimentary ribs are known to likely disappear during further development. The NO(A)EL for maternal toxicity was 55 mg/kg bw and the NO(A)EL for fetal development was 110 mg/kg bw/day.

The implementation of a developmental toxicity study in a 2ndspecies is scientifically unjustified because no teratogenic effects are expected due to concentration-dependent local effects.

After hydrolysis, irritant/corrosive effects of formaldehyde are expected; local maternal effects but no developmental effects have been reported in inhalation studies. In oral studies no developmental toxicity occurred at dose levels inducing local maternal toxicity. Data on ethylene glycol indicated skeletal malformation at oral dose levels of 500 mg/kg and above, however, ethylene glycol is no hydrolysis product of concern as shown in the 90-Day oral toxicity study. Likewise no relevant contribution to the developmental toxicity for urea is expected.


Justification for classification or non-classification

Additional information