3-chloropropene

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
A final statement on bioaccumulation potential of 3-chloropropene is not possible, but a low bioaccumulation potential can be expected.
It is easily absorbed the oral route and the inhalative route and very likely also via the dermal route.
Distribution is fast via the blood circulation and not hindered by blood tissue barriers.
3-chloropropene is metabolised extensively and excreeted mainly via urine and via exhalation (either unchanged or as CO2)

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

3 -chloropropene is readily absorbed via the gastrointestinal tract and via the inhalative route as has been shown in Waechter (1982). Based on the information from NIOSH (1976) / (summary dossier on the toxicology of 3-chloropropene - skin irritation in workers) (chapter 7.3.1) that 3 -chloropropene caused a deep seated pain after occupational dermal exposure, a significant bioavailability via the dermal route has to be expected as well.

Detailed data on distribution is not available. Given that 3-chloropropene is apolar, has a low molecular weight of 76,53 g/mol and has a Log Pow of 2.1 it can be expected that the substance is readily distributed throughout the body via the blood circulation.

The substance is extensively metabolised as long as the metabolic capacities are not exploited (as at 100 mg/Kg bw in the rat). Allylmercapturic acid, sulfoxide of allylmercapturic acid, allylcysteine and hydroxypropylmercapturic acids were unambiguosly identified as metabolites of 3-chloropropene in rats (Kaye (1972) / (CFE rats, identification of urinary metabolites of 3-chloropropene)).

Main routes of excretion are the urine, exhalation and to a lesser extent the feces.

As absorption, distribution, metabolism and excretion are expected to be comparable for 3 -chloropropene in rodents and humans (and other mammals) the above stated conclusions can be extended, at least qualitatively, also to humans (and other mammals)

A final statement on bioaccumulation potential of 3-chloropropene is not possible based on the available data, but a low bioaccumulation potential can be expected which is in line with the summary on ADME of the BUA report 186 (1995) on 3 -chloropropene.

Discussion on bioaccumulation potential result:

The key study of Waechter (1982) / (male F344 rats, toxicokinetic studies including 3 exposure routes) describes the absorption, toxicokinetic and excretion of 3-chloropropene in rats after exposure to 1 and 100 mg/Kg bw via gavage and iv injection and to 10, 100, 1000 and 2000 ppm for 6 h via inhalation. Kaye (1972) / (CFE rats, identification of urinary metabolites of 3-chloropropene) describes the identification of metabolites of 3-chloropropene in urine and bile in the rat after sc injection of 1 mL (= 940 mg/animal = approximately 235mg/Kg bw). The BUA reports adds some informationon the partition coefficients between tissues and air as an approximation for bioaccumulation potential of the substance.

Absorption:

3-chloropropene is readily absorbed via the gasrointestinal tract as well as via inhalation (absorption rates for inhalation are 0.89, 9.83, 63.9 and 67.5 μg/min for 10, 100, 1000 and 2000 ppm for 6 h respectively), distributed quickly and extensively metabolised especially at lower doses (1 mg/Kg bw orally). After oral gavage with 1 mg/Kg bw at least 70 % absorption can be assumed while after treatmant with 100 mg/Kg bw at least 42.2 % absorption can be assumed (Tmax < 1 h and = 4 h respectively).Waechter (1982)

 

Distribution:

Detailed data on distribution is not available. Given that 3-chloropropene is apolar, has a low molecular weight of 76,53 g/mol and has a Log Pow of 2.1 it can be expected that the substance is readily distributed throughout the body via the blood circulation.

Metabolism:

3-chloropropene is metabolized extensively, especially at lower doses (1 mg/Kg bw orally).At higher doses (100 mg/Kg bw orally) 3 -chloropropene is exhaled to a significant amount unmetabolised. A 100 mg/kg oral dose would be approximately equivalent to a six hour-150 ppm inhalation exposure and a 100 mg/kg intravenous dose would be approximately equivalent to a six hour-85 ppm exposure. Waechter (1982)

Allylmercapturic acid, sulfoxide of allylmercapturic acid, allylcysteine and hydroxypropylmercapturic acids were unambiguosly identified as metabolites of 3-chloropropene in rats by chromatographic techniques and by isolation from urine.Kaye (1972)

 

Excretion:

Primary routes of excretion are the urine and the exhalation (either unchanged or as CO2). At higher doses (100 mg/Kg bw) 3 -chloropropene is exhaled to a significant amount unmetabolised.The half-life of 3 -chloropropene in blood after treatment with 100 mg/Kg via gavage is t1/2 = 2.58 h, after 100 mg/Kg via iv injection t1/2 = 23.5 min and after inhalation of 100 ppm for 6 h t1/2 = 16.7 min. Waechter (1982)

 

Relevance for humans and other mammals:

As absorption and distribution of 3 -chloropropene in rodents are mainly driven by its physico-chemical properties it is assumed that a comparable situation is found in humans and other mammals. As the metabolism comprises glutathione coupling and possibly also cytochrome P450 catalysed oxidation in rodents, a comparable metabolism is expected for humans, though the turnover might be slower as rodent generally have a faster metabolism than humans.

Based on this findings the target organs and the route of excretion are also expected to be the same in humans and other mammals.

A final statement on bioaccumulation potential of 3-chloropropene is not possible based on the available data, but a low bioaccumulation potential can be expected which is in line with the summary on ADME of the BUA report 186 (1995) on 3 -chloropropene.