3-chloropropene

Endpoint summary

Description of key information

- Oral:           LD50: 275 mg/kg bw (180 — 526, 95 % CL) for the rat (OECD TG 401); study Henck (1980)
- Dermal:        LD50: 398 mg/Kg bw  for the rabbit (non-guideline test); Dow K-1720-4A
- Inhalation: LC50: 2900 mg/kg bw for the male guinea pig (generally compliant to OECD TG 403); study Lu (1982)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

275 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

2 900 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

398 mg/kg bw

Additional information

- oral toxicity: The value for the key parameter of 275 mg/kg bw (180 — 526, 95 % CL) is based on the lowest observed value in a study considered to be reliable Henck (1980) in the rat. The other studies including one for mice (Lu, 1982) are all unreliable due to very limited details on methods and results. In addition the values stated there are higher (Lu 1982, rats: 460 mg/Kg, Lu 1982, mice: 425 mg/Kg, Smyth 1948, rats: 700 mg/Kg) indicating that the key value is set at a conservative benchmark. Clinical signs are lethargy, diarrhea, hind limb paralysis, piloerection and convulsions severity of clinical signs is dose dependent. As adverse effects based on histology irritation base lesions like stomach thickening and roughening of nonglandular squamous epithelium, focal thickening of nonglandular stomach wall, erosion of nonglandular epithelium and finally perforated ulcers were found at very high doses at the portal of entry, cloudy swelling and focal necrosis is found in liver and kidneys. In addition lung pulmonary congestion and edema with hemorrhages into the alveolar spaces are described by (Lu 1982) but it is unclear whether this is a result of aspiration.

- dermal toxicity: The value for the key parameter of 398 mg/kg bw is based on the study Dow K-1720-4A. The study itself is not reliable due to very limited information available on methods and animal husbandry. Nevertheless given the reported good skin absorption of 3 -chloropropene and its fast and thourough distribution throughout the body after absorption, a dermal toxicity comparable to the toxicity via the oral and the inhalation route can be expected, especially as the reported death occured probably due to cyanosis, which was a key adverse effect in the toxicity via the other routes. This assumption supports the LD50 value derived in study Dow K-1720-4A.

- inhalation toxicity: The value for the key parameter of LC50(4h exposure) = 2900 mg/m³ is based on the lowest deducible LC50 value in guinea pigs in a weight of evidence approach combining the following studies: Lu (1982, mouse, rat, guinea pig, rabbit, cat), Quast (1982, rat and mouse) and Adams (1944, rat and guinea pig). The value is an extrapolation of the LC50 of 5800 mg/m³ after 2 h of exposure. Quast is the best reported study and has thereby the highest reliability. But as animals of the dose groups were killed at different time points between 3 and 7 days post treatment, a clear LC50 could not be derived. Nevertheless the approximation of 3100 mg/m³ (1000 ppm) is in good accordance with the value derived from Lu (1982) thereby validating the latter as reliable.

Typical clinical signs after exposure to high (lethal) concentrations are indicative for the irritative action of 3 -chloropropene: closing eyes, pawing, scratching the nose and mouth, lacrimation and salivation. Systemic effects becoming obvious during exposure are comparable to effects seen after oral exposure: hypoactivity, hypopnea, paralysis of hind limbs, drowsiness, unconsciousness, tremor and convulsions.

Guseinov (1983) / (rat, acute inhalative toxicity) reports a NOAEC of 104 mg/m³ based on adverse effects serum choline esterase and neurobehavioural findings (burrow reflex). As the analytical method used in this study is based on colourimetric assays and not described in detail the stated threshold values are highly questionable and regarded as unreliable.

Justification for classification or non-classification

- oral toxicity: 3 -chloropropene is moderately toxic via the oral route based on systemic effects that lead to respiratory arrest. Classification as Category III (H301: toxic if swallowed) is considered to be required according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- dermal toxicity: Using a weight of evidence approach based on results from a non-guideline study and toxicokinetic informations 3 -chloropropene is evaluated to be moderately toxic in contact with the skin.

Classification as Category III (H301: toxic in contact with skin) is considered to be required according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

- inhalation toxicity: 3 -chloropropene is moderately toxic via the inhalation based on systemic effects that lead to respiratory arrest. Classification as Category III (H331: toxic if inhaled) is considered to be required according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.