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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
251.5 mg/m³
Additional information

A screening study for reproductive/development toxicity is waived on the basis of the availability of a full study investigating reproductive toxicity in a single generation study in which rats were exposed by the primary exposure route - inhalation. 

The reproductive effects of 2,3 dichloro-1,3 butadiene have been assessed in a guideline compliant (OECD Guideline 415) one-generation reproductive study rather than a two generation study as specified in REACH test guidelines. However, in the absence of any adverse findings and the EU indications of moving to replace the 2-generation study with data from a single generation study, it is considered that the study presented here adequately addresses the requirements of this annex point.

The effects of 2,3 dichloro-1,3 butadiene on fertility were investigated in a guideline-compliant (OECD Guideline 415) one generation reproduction toxicity study in which groups of Crl:CD®(SD)IGS BRrats (24/sex/concentration) were exposed by whole body inhalation to vapours at 0, 1, 5, or 50 ppm. Rats were exposed for 6 hours/day during premating (8 weeks; 5 days/week), during cohabitation of mating pairs (up to 2 weeks, 7 days/week), and then post-cohabitation for males and nonpregnant females (approximately 7 days, 7 days/week). The pregnant dams were exposed from conception to implantation (days 0-7 of gestation). In parental rats, no treatment-related effects were observed on mortality, clinical parameters, oestrous cycle and sperm parameters; mating, precoital interval and fertility; gross observations and organ weights. Treatment-related effects evident at 50 ppm were decreased body weight and weight gain, food consumption and efficiency and degeneration of the nasal olfactory epithelium.

No effects on fertility were observed in the study. The no-observed-effect level (NOEL) for reproductive and developmental toxicity was reported as 50 ppm, the highest concentration tested. The NOEL for repeated dose inhalation toxicity in parental rats was 5 ppm based on observations of reduced body weight, bodyweight gain and food consumption parameters, and degeneration of the nasal olfactory epithelial toxicity at 50 ppm (251.5 mg/m3).


Short description of key information:
No effects on fertility were observed in a guideline compliant one-generation reproduction toxicity study in which rats were exposed to 2,3 dichloro-1,3 butadiene by whole body inhalation at concentrations up to 50 ppm. The NOEL for reproductive toxicity was reported as 50 ppm (251.5 mg/m3): the highest dose tested.

Effects on developmental toxicity

Description of key information
No developmental effects were observed in offspring from rats exposed to 2,3 dichloro-1,3 butadiene by inhalation at concentrations up to 50 ppm in a one-generation reproduction toxicity study. The NOEL for developmental toxicity was reported as 50 ppm, the highest dose tested. In a guideline-compliant prenatal developmental toxicity study in which pregnant rats were exposed to 2,3 dichloro-1,3 butadiene by whole body inhalation at concentrations 0,1, 10, or 50 ppm, the NOEL for maternal and developmental toxicity was reported as 10 ppm (50.3 mg/m3) based on decreased maternal body weight gain, food consumption and clinical signs of toxicity and developmental toxicity respectively.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
50.3 mg/m³
Additional information

The developmental effects of 2,3 dichloro-1,3 butadiene have been assessed in a guideline compliant (OECD Guideline 415) one-generation reproductive study rather than a two generation study as specified in REACH test guidelines. However, in the absence of any adverse findings and the EU indications of moving to replace the 2-generation study with data from a single generation study, it is considered that the study presented here adequately addresses the requirements of this annex point.

The effects of 2,3 dichloro-1,3 butadiene on early embryonic development were investigated in a guideline-compliant one-generation reproduction study in which groups of Crl:CD®(SD)IGS BRrats (24/sex/concentration) were exposed by whole body inhalation to vapours at 0, 1, 5, or 50 ppm. Rats were exposed for 6 hours/day during premating (8 weeks; 5 days/week), during cohabitation of mating pairs (up to 2 weeks, 7 days/week), and then post-cohabitation for males and non-pregnant females (approximately 7 days, 7 days/week). The pregnant dams were exposed from conception to implantation (days 0-7 of gestation). No treatment-related effects were observed on the number of corpora lutea; implantation sites, resorptions, live foetuses; pre- and post implantation loss and foetal weight, sex ratio, and external alterations.

No adverse affects were observed in offspring from rats exposed to 2,3 dichloro-1,3 butadiene by inhalation. The no-observed-effect level (NOEL) for developmental toxicity was reported as 50 ppm, the highest concentration tested.

In a guideline-compliant (OECD Guideline 414) prenatal developmental study, groups of 22 time-mated pregnant female Crl:CD®(SD)IGS BRrats were exposed by whole body inhalation to 2,3 dichloro-1,3 butadiene at 0,1, 10, or 50 ppm for 6 hours per day during gestation days 6-20. No treatment-related maternal mortality or gross post-mortem findings were observed. Maternal toxicity, characterized by statistically significant, treatment-related reductions in body weight, weight gain, and food consumption was observed at 50 ppm. Gasping and laboured breathing were also observed in rats exposed to 2,3 dichloro-1,3 butadiene at 50 ppm. Mean fetal weight was significantly reduced by 6.2 % in foetuses from treated at 50 ppm. No treatment-related malformations or variations were observed: fetal viability, resorptions, sex ratio, and litter size were comparable across all groups.

The maternal and fetal NOELs in rats following inhalation exposures were both considered to be 10 ppm (50.3 mg/m3), based on decreased maternal body weight gain, food consumption and clinical signs of toxicity and developmental toxicity respectively.

Justification for classification or non-classification

There is insufficient evidence to classify 2,3 dichloro-1,3 butadiene for reproductive or developmental toxicity