2-chlorobuta-1,3-diene

Endpoint summary

Description of key information

Acute investigations are available for oral and inhalation routes of exposure and some limited data are available for acute topical exposure.  For Chloroprene an oral LD50 value of 251 mg/kg bw in rats was determined (Asmamgulian 1971). For the endpoint acute toxicity: inhalation formal median lethal dose levels were not established in compliance with current test procedures but lethal dose levels have been identified using alternative evaluative methods ((Anon 1970, 1971, 1974 and  Plugge1979).  Data from secondary litertature indicate an LC50 of 11800 mg/m3/4h in rats Izmerov 1982).
In a limited dermal toxicity study no mortality was observed after single dermal exposure with 200 mg/kg bw (Anon 1970).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

251 mg/kg bw

Additional information

Acute toxicity

The acute toxicity of chloroprene has been reported in several non-standard studies. Acute oral LD₅₀and inhalation LC₅₀values have been reported in published literature. 

Acute oral toxicity

Izmerov et al (1982) reported acute oral (gavage) LD₅₀values of between 146 and 260 mg/kg bw for mice and between 251 and 450 mg/kg bw for rats. The LD50 values of 251 mg/kg for rats and 260 mg/kg bw for mice based on the most relevant study data

Asmangulian (1971).

In an oral toxicity study in rats, a single dose of chloroprene at 50 mg/kg bw did not cause any mortality. In another, poorly reported study in rats from the 1930s, 80% of animals died after a single oral dose (gavage route) of 0.5 cc of chloroprene whereas 33% died after a single 0.4 cc dose. A dose of 0.2 cc resulted in depression with recovery. On the basis of this study, chloroprene did not meet the criteria for classification as a Class B poison via the oral route. Official EU Classification DSD: R20/22.

Acute inhalation toxicity

Izmerov et al (1982) reported a 2-hour inhalation LC₅₀value of 3480 (3000-4000) mg/m³in mice and a 4-hour inhalation LC₅₀of 11800 (10500-13200) mg/m³in rats.

Acute inhalation toxicity studies on chloroprene were conducted in the 1970s and pre-date current testing guideline. These were generally well designed and can be regarded as reliable. In an acute inhalation toxicity study, young male albino rats (ChR-CD strain) were exposed to chloroprene vapours at various concentrations for a single 4 hour period. The approximate lethal concentration (ALC; 1 or more deaths observed) for four hours was 8.42 mg/litre. A median lethal concentration could not be determined from the results. Exposed rats showed laboured respiration and pallor, with severe weight losses and deaths at exposures at 8.42 mg/L and above. Exposed rats had severe lung and liver damage, which partially recovered by 14 days post-exposure. Chloroprene was classified as slightly toxic compound via the inhalation route.

Chloroprene did not meet the criteria for classification as a Class B poison via the inhalation route in two Class B poison tests in which male ChR-CD rats or ChR-CL rats were exposed to chloroprene vapours at 72.4 mg/L air (36 times the concentration required for labelling) or 57.5 mg/L air respectively for 1 hour,. The inhalation 1 hour LC₅₀was found to exceed 72.4 mg/L and exceeded the 5 mg/L limit dose for testing under current EU guidelines.

In an acute inhalation study, fasted male Sprague-Dawley rats were exposed to chloroprene at 0, 100, 150, 225 and 300 ppm for 4 hours and killed 24 hours later (Plugge1979).Animals exposed to 150, 225 and 300 ppm had a significant increase in liver to body weight ratio. Lung to body weight ratios did not demonstrate any treatment-related differences between groups.Liver injury, as measured by increased serum sorbitol dehydrogenase (SDH) activity was apparent in animals exposed to 225 and 300 ppm.Non-protein sulfhydrylNPSH concentrations in the liver increased significantly in all treated groups and at 300 ppm was more than double that seen in the controls. Lung NPSH was decreased at 100 and 300 ppm (not measured at 150 and 225 ppm).The authors concluded that the threshold for hepatic toxicity in fasted rats due to chloroprene inhalation was between 160 and 180 ppm for 4 hours. After this threshold was exceeded hepatic injury progressed exponentially. Pretreatment with Aroclor 1254 protected against chloroprene induced liver damage, as measured by serum SDH elevation, liver enlargement and NPSH rebound. Since 90% of the increase or rebound in NPSH concentrations was glutathione (GSH), the authors proposed that GSH has a key role in the metabolism of chloroprene. Official EU Classification DSD: R20/22

Acute dermal toxicity

Chloroprene did not meet the criteria for classification as a Class B poison via the skin absorption route based on no mortalities being observed in a limited study of male albino rats exposed dermally (occluded via clipped trunks) to a single dose at 200 mg/kg BW. Therefore Chloroprene is not classified in the EU regarding acute dermal toxicity.

Justification for classification or non-classification

According to Annex VI to Regulation (EC) No 1272/2008, chloroprene is classified for acute toxicity hazard as: Acute Tox 4 (H302) – Harmful if swallowed. On the basis of the quantitiative LD50 data for chloroprene reported (Asmamgulian 1971), the following classification is proposed for the acute oral toxicity of chloroprene: Acute oral toxicity - Acute Tox 3 (H301) - Toxic if swallowed.

According to Annex VI to Regulation (EC) No 1272/2008, chloroprene is classified for acute toxicity hazard as: Acute Tox 4 (H332) – Harmful if inhaled and for specific target organ toxicty (STOT) for single exposures as STOT Sinlge Exp 3 (H335): may cause respiratory irritation (Affected organs: lung,liver and kidney; route of exposure: inhalation);