Buta-1,2-diene

Endpoint summary

Description of key information

There are no repeat dosing studies carried out on 1,2-butadiene itself but a weight of evidence evaluation of repeat dosing studies with 1,3-butadiene  and the mono-butene isomer, 2-methylpropene isomer indicates that 1,2-butadiene has low potential for repeat dose toxicity. The NOAEC of 1000 ppm (2212 mg/m3) is based on the NOAEC for 1,3-butadiene in rats.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

2 212 mg/m³

Additional information

1,2-Butadiene is a gas and therefore exposure via the dermal or oral routes is unlikely. No studies using these routes are available for 1,2-butadiene. The requirement for data on repeat dose oral and dermal toxicity is waived in accordance with REACH Annex XI, as 1,2-butadiene is a flammable gas at room temperature.

 

There are no repeat dosing studies carried out on 1,2-butadiene itself, however, in accordance with the strategy described in Section 7.1 (Toxicokinetics endpoint summary) repeat dosing studies in the rat on the structural analogue 1,3-butadiene, are used here for read across. Repeat dosing studies in the mouse and rat on the mono-butene isomer, 2-methylpropene, are also used to provide weight of evidence.

In the rat, exposure to 1,3-butadiene results in low toxicity. The most comprehensive information in the rat is available from a carcinogenicity study (Owen et al, 1987). In this key study, male and female rats were exposed to 1,3-butadiene at 0, 1000, or 8000 ppm (0, 2212 or 17701 mg/m³), 5 days/week, for up to 2 years. There were no effects on haematology, blood chemistry, urine analysis and neuromuscular function that were associated with treatment. Non-neoplastic findings were limited to changes in clinical condition, suppression of body weight gain, reduced survival, increased weights of liver, kidney, heart, lung and spleen, nephrosis of the kidney and focal metaplasia in lung. The neoplastic changes are described in the Section on Carcinogenicity. A NOAEC of 1000 ppm (2212 mg/m³) for systemic toxicity was established based on some minimal toxic effects (increased heart weight and kidney nephrosis) occurring at 8000 ppm. 

In other studies in rats, inhalation exposure of rats to 1,3-butadiene at concentrations of 1000, 2000, 4000 and 8000 (2212, 4425, 8850 and 17701 mg/m³) for 13 weeks produced no treatment-related effects except moderately increased salivation. There were no effects on growth rate, food consumption, haematology, clinical chemistry, urine analysis or macroscopic and histopathological effects. In this study the NOAEC for 1,3-butadiene in the rat was 8,000 ppm (17,701 mg/m³) (Crouch et al 1979). Similar results were reported by Bevan et al (1996), where rats were exposed to 1,3-butadiene at a single concentration of 1000 ppm (2212 mg/m³) for 13 weeks. There were no effects other than minor increases in liver and kidney weights in male rats. Hyaline droplet formation was observed in the kidneys of 20% of treated rats but there was no cytotoxicity associated with this. None of the effects were considered to be adverse. 

 

Inhalation studies on 2-methylpropene (isobutylene) in rats and mice conducted by the NTP (1998) also support the data on 1,3-butadiene. F344/N rats and B6C3F1 mice were exposed to 2-methylpropene at concentrations of 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm, (1147, 2294, 4589, 9179, 18359 mg/m³) for 14 weeks. There were no significant exposure-related toxicological effects in either species at any dose level. Increased kidney weights in mice; and increased liver and kidney weights and minimal hypertrophy of goblet cells lining the nasopharyngeal ducts in rats, were considered to be non-toxic adaptive responses (NTP 1998). The NOAEL for both studies was 8000 ppm (18,359 mg/m³) the highest concentration level tested.

 

In conclusion, the weight of evidence from 1,3-butadiene and 2-methylpropene indicates that 1,2-butadiene has low potential for repeat dose toxicity. The NOAEC of 1000ppm (2212 mg/m³) is based on the NOAEC for 1,3-butadiene in rats in the key chronic study of Owen et al (1987) and is supported by the sub chronic data on both 1,3-butadiene and 2-methylpropene.

There are no repeat toxicity data on 1,2 -butadiene in humans.

Justification for classification or non-classification

1,2-Butadiene is a flammable gas at room temperature and therefore dermal and oral exposure is unlikely. It has low sub-chronic inhalation toxicity and therefore does not warrant classification under Dir 67/548/EEC or GHS/CLP.