3-chloropropene

Endpoint summary

Description of key information

- Repeated dose toxicity, oral: no reliable study available
- Repeated dose toxicity, dermal: no study available
- Repeated dose toxicity, inhalation: NOAEC = 10 ppm (=31 mg/m³) for the rat, (neurotoxicity study); Nagano 1991

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

31 mg/m³

Additional information

- Repeated dose toxicity, oral: No reliable study could be retrieved describing the toxicity of 3 -chloropropene after repeated oral exposure. Only He 1985 reports marked neurodegenerative effects in TO albino mice after oral treatment via gavage of 300 and 500 mg/Kg bw 3d/wk for 3 months. Nevertheless the reported details on the used methods and results are so limited that a reliable assessment is not possible.

- Repeated dose toxicity, dermal: No study on dermal toxicity of 3 -chloropropene after repeated dermal exposure could be retrieved.

- Repeated dose toxicity, inhalation: The NOAEC of 31 mg/m³ (10 ppm) is based on the neurotoxic effects as shown in the study of Nagano (1991, rats, 2 x 4 h/d and 5 d/wk for a period of 34 wks). At 310 mg/m³ (100 ppm) reduction of motor and sensory nerve conduction velocities and nerve action potentials (NAP) after 28 wk when clinical signs of neuropathy were observed, i.e., weakness of hind limbs and . In addition motor distal latency was retarded in rats of this high dose group at the last period of exposure. In the 50 ppm group a decreased nerve action potentials was found. Other systemic effects at higher doses like tubules with focal collapse and atrophy in rat kidneys and raised relative kidney weights in mice at 100 ppm and additionally slightly exaggerated glycogen accumulation at 250 ppm in mice are reported by the reliable, guideline compliant study of Quast (1982, rats, 90 d, 6h/d, 5d/wk). Mice used in the same study were generally less susceptible for the toxicity of 3 -chloropropene. Neurotoxic effects are also stated by Lu 1982 in rats rabbits and cats but due to the wide spreading of the doses (low: 5.6 ppm = 17.5 mg/m³ = NOAEC, high: 66.5 ppm = 206 mg/m³ = LOAEC) no reliable threshold value can be derived.

Torkelson (1959, rats, guinea pigs, rabbits, dogs; 7h/d, 5 d/wk, 180 d) reported a NOAEC of 9 mg/m³ (3 ppm) based on marked liver and kidney effects at the high dose. This study is regarded as unreliable as the study does not follow a approved guideline and uses only a very limited amount of animals. The analytical method is not described in details. Therefore the significance of the derived threshold value is questionable. This evaluation is in line with the OECD SIDS report on 3 -chloropropene, p. 79 (for bibliographic source, including a hyperlink please refer to the endpoint study report):

"In view of the small number of test animals and poor reporting of the results as well as contradiction of these findings by better designed studies (e.g. Quast et al., 1982), this older study is considered to be not suitable for derivation of an overall NOAEC."

Guseinov (1983, rats, 4 h/d, 5 days/week, 4 months) reports a NOAEC of 0.29 mg/m³ and a corresponding LOAEC of 1.1 mg/m³

) based on raised serum cholin esterase levels indicative for liver toxicity and neurotoxic effects (neurotransmission measurements and neurobehavioural tests). Nevertheless this study is regarded as scientifically unreliable and inapplicable for the hazard assessment as it lacks information on animals source and husbandry, information on individual data, information on exposure methods and especially information on analytical determination of exposure concentration. This is in-line with OECD SIDS report on 3 -chloropropene where this study was disregarded for risk assessment and derivation of a NOAEC. The derived NOAEC of 10 ppm (31 mg/m³) based on experimental data in animals is thereby in accordance with the risk assessment for repeated dose toxicity in the OECD SIDS report on 3 -chloropropene which was approved at the 4th SIAM (Tokyo, 20-22 May 1996). He 1985 A reports (chapter 7.10.2) comparable adverse effects in humans. Polyneuropathia was seen in total 53 workers of two production sites after exposure to 3-chloropropene vapours leading to showed symmetrical distal sensory deficits and there was decreased muscular strength. Adverse effects on liver or kidneys were not noted though respective parameters were explicitly checked. The exposure limits of the individuals are unclear. For site A (26 female workers) levels of 2.6 - 6'6650 mg/m³ (= 0.84 - 2'145 ppm, factory A, 1970 - 1977, duration: 2.5 mo - 6 yrs) are reported, for site B 0.2 - 25.13 mg/m³ (= 0.065 - 8.1 ppm, factory B, 1978 - 1982, duration: 1 - 4.5 yrs). Due to this uncertainty in exposure the study is not suitable as base for a risk assessment. Nevertheless the authors propose a occupational exposure limit of (2 mg/m³) 0.66 ppm, comparable to the value derived by the OECD SIDS report on 3 -chloropropene (3.1 mg/m³, 1 ppm)

Justification for classification or non-classification

- Robust data on repeated dose toxicity of 3 -chlororpropene is only available for inhalative exposure. Given the small size of the molecule and a logPow of 2.1 a fast distribution in the organism is presumed and thereby comparable results are expected for oral or dermal exposure.

Based on the results of repeated dose inhalative studies in rats 3 -chloropropene is classified as STOT RE1 (H372: Causes damage to organs through prolonged or repeated exposure (nervous system, liver and kidneys)).