3-chloropropene

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro

Remarks:

Type of genotoxicity: other: summary on gene mutation, chromosome aberration, DNA damage and/or repair and genome mutation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: summary of summaries on in vitro genetic toxicity testing of two regulatory dossiers

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

5.5 Genetic Toxicity 'in vitro'

Author:

Sijm D.

Year:

1996

Bibliographic source:

OECD Screening Information DataSet (SIDS) High Production Volume Chemicals (Processed by UNEP Chemicals), SIDS Initial Assessment Report for the 4th SIAM - CHLOROPROPENE CAS No: 107-05-1, p. 87 - 91; http://www.inchem.org/pages/sids.html

Reference 2

Reference Type:

secondary source

Title:

ALLYL CHLORIDE

Author:

N.N.

Year:

1999

Bibliographic source:

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 71, Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide, IARC Lyon, France, p. 1231

Materials and methods

Type of assay:

other: different types of tests

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropene

EC Number:

203-457-6

EC Name:

3-chloropropene

Cas Number:

107-05-1

Molecular formula:

C3H5Cl

IUPAC Name:

3-chloroprop-1-ene

Method

Test concentrations with justification for top dose:

see table 1

Results and discussion

Test results

Species / strain:

other: different test systems

Metabolic activation:

with and without

Genotoxicity:

other: positive and negative findings, see table 1

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

other: not applicable

Untreated negative controls validity:

other: not applicable

Positive controls validity:

other: not applicable

Additional information on results:

Different studies have been conducted including the bacterial reverse mutation assay (Ames Test), Aspergillus nidulans forward mutation assay, in-vitro cytogenetic assays in mammalian cell lines, UDS assays in mammalian and human cell lines and DNA binding studies. The DNA binding study was reported to be positive. For the other studies both positive and negative results have been found for 3-chloropropene with and without activation where results are usually more critical without activation. In general high concentrations are needed to elicit genotoxic effects.

Remarks on result:

other: other: a variety of test systems

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1. Genetic and related effects of allyl chloride

Test system	Result^a		Dose^b(LED or HID)	Reference
	Without exogenous metabolic system	With exogenous metabolic system
Salmonella typhimurium TA100, reverse mutation, spot test and plate test	+	+	4700 µg/plate	Bignami et al. (1980)
Salmonella typhimurium TA1535, reverse mutation, spot test and plate test	+	(+)	4700 µg/plate	Bignami et al. (1980)
Streptomyces coelicolor, forward mutation	+	NT	9400 µg/plate	Bignami et al. (1980)
Streptomyces coelicolor, reverse mutation	+	NT	9400 µg/plate	Bignami et al. (1980)
Aspergillus nidulans, forward mutation	–	NT	37600 µg/plate	Bignami et al. (1980)
Salmonella typhimurium TA100, reverse mutation	+	(+)	5740 µg/plate	Eder et al. (1980)
Salmonella typhimurium TA100, reverse mutation	+	(+)	NG	Eder et al. (1982)
Binding (covalent) to DNA in vitro	(+)	NT	9000	Eder et al. (1987)
Chromosomal aberrations, Chinese hamster lung CHL cells in vitro	+	+	400	JETOC (1997)
Escherichia coli pol A+/pol A– differential toxicity (spot test)	+	NT	9400 µg/disk	McCoy et al. (1978)
Salmonella typhimurium TA100, reverse mutation, substance immersed in a disc,	–	–	9400 µg/disk	McCoy et al. (1978)
Salmonella typhimurium TA1535, reverse mutation, substance immersed in a disc,	(+)	+	940/disk	McCoy et al. (1978)
Salmonella typhimurium TA1538, reverse mutation, substance immersed in a disc	–	–	9400/disk	McCoy et al. (1978)
Salmonella typhimurium TA1535, reverse mutation, pre-incubatin test	+	+	940 µg/plate	McCoy et al. (1978)
Saccharomyces cerevisiae D4, gene conversion	+	NT	14 mg/L	McCoy et al. (1978)
Salmonella typhimurium TA100, reverse mutation	(+)	+	2130 µg/plate (20 pre-incubation 532 µg/plate (120 min preincubation)	Neudecker & Henschler (1985)
Salmonella typhimurium TA100, reverse mutation	NT	+	-	Neudecker & Henschler (1986)
Salmonella typhimurium TA100, reverse mutation	+	NT	0.02	Norpoth et al. (1980)
Salmonella typhimurium TA100, reverse mutation	+	NT	0.05^c	Simmon (1981)
Escherichia coli WP2, reverse mutation, spot test	+	+	18800^d	Dean (1985)
Escherichia coli WP2 UVRA, reverse mutation, spot test	+	+	18800^d	Dean (1985)
Salmonella typhimurium TA98, reverse mutation	-	-	2000	Dean (1985)
Salmonella typhimurium TA100, reverse mutation	-	-	2000	Dean (1985)
Salmonella typhimurium TA1535, reverse mutation	-	-	2000	Dean (1985)
Salmonella typhimurium TA1538, reverse mutation	-	-	2000	Dean (1985)
Rat liver RL1, cytogenetic assay	+	+	>= 25 mg/L	Dean (1985)
Aspergillus nidulans, induction of somatic segregation	+		45 ppm	Crebelli 1984
HeLa cells, UDS assay + Ames-test	+	+		Schiffmann 1983
UDS assay in human embryonic intestinal cells	-	-	9900 µg/mL	McGregor, NIOSH 1981

In italics: values directly extracted from “IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 71, Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide, IARC Lyon, France, p. 1231;http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php” without further assessment

a +, positive; (+), weak positive; –, negative; NT, not tested

b LED, lowest effective dose; HID, highest ineffective dose; in-vitro tests, µg/mL; NG, not given

c Cells were exposed to allyl chloride vapour; dose = µg/mL in air.

d 20 µL in the spot test

references:

Bignami M, Conti G, Conti L, Crebelli R, Misuraca F, Puglia AM, Randazzo R, Sciandrello G, Carere A. Mutagenicity of halogenated aliphatic hydrocarbons in Salmonella typhimurium, Streptomyces coelicolor and Aspergillus nidulans. Chem Biol Interact. 1980 Apr;30(1):9-23.

 

Crebelli R, Conti G, Conti L, Carere A. Induction of somatic segregation by halogenated aliphatic hydrocarbons in Aspergillus nidulans. Mutat Res. 1984 Oct;138(1):33-8.

 

Dean BJ, Brooks TM, Hodson-Walker G, Hutson DH. Genetic toxicology testing of 41 industrial chemicals.Mutat Res. 1985 Jan-Mar;153(1-2):57-77

 

Eder E, Neudecker T, Lutz D, Henschler D. Mutagenic potential of allyl and allylic compounds. Structure-activity relationship as determined by alkylating and direct in vitro mutagenic properties. Biochem Pharmacol. 1980 Apr 1;29(7):993-8.

 

Eder E, Neudecker T, Lutz D, Henschler D. Correlation of alkylating and mutagenic activities of allyl and allylic compounds: standard alkylation test vs. kinetic investigation. Chem Biol Interact. 1982 Feb;38(3):303-15.

 

Eder E, Lutz D, Jörns M. Allylic compounds bind directly to DNA: investigation of the binding mechanisms in vitro. Chem Biol Interact. 1987 Feb;61(2):97-108.

 

IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 71, Re-evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide, IARC Lyon, France, p. 1231; http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php

 

JETOC. Mutagenicity Test Data of Existing Chemical Substances, Suppl.,,. Chemical Industry Ecology–Toxicology and, 1997 pp. 278–279

 

McCoy EC, Burrows L, Rosenkranz HS. Genetic activity of allyl chloride. Mutat Res. 1978 Mar;57(1):11-5.

 

McGregor D.B. IRI report to NIOSH NTIS no. PB86-239845, 1981 Jul 1.

 

Neudecker T, Henschler D. Mutagenicity of chloroolefins in the Salmonella/mammalian microsome test. III. Metabolic activation of the allylic chloropropenes allyl chloride, 1,3-dichloropropene, 2,3-dichloro-1-propene, 1,2,3-trichloropropene, 1,1,2,3-tetrachloro-2-propene and hexachloropropene by S9 mix via two different metabolic pathways. Mutat Res. 1986 Apr-May;170(1-2):1-9.

 

Neudecker T, Henschler D. Mutagenicity of chloro-olefins in the Salmonella/mammalian microsome test. I. Allyl chloride mutagenicity re-examined. Mutat Res. 1985 Aug-Sep;157(2-3):145-8.

 

Norpoth, K., Reisch, A. & Heinecke, A. Biostatistics of Ames-test data. In: Norpoth, K.H. & Garner, R.C., eds,Short-term Test Systems for Detecting Carcinogens, New York, Springer- Verlag, 1980, pp. 312–322

 

Schiffmann D, Eder E, Neudecker T, Henschler D. Induction of unscheduled DNA synthesis in HeLa cells by allylic compounds. Cancer Lett. 1983 Oct;20(3):263-9.

 

Simmon, V.F. Applications of theSalmonella/microsome assay. In: Stich, H.F. & San, R.H.C., eds,Short-term Tests for Chemical Carcinogens,, Springer-Verlag, 1981; pp. 120–126

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
other: positive and negative results depending on test system and conducting laboratory

In 29 different tests on genetic toxicity of 3-chloropropene positive and negative results depending on test system and conducting laboratory were found. The overall results are therefore ambiguous, following a conservative approach the substance can be regarded as positive for in vitro genotoxicity.

Executive summary:

The results of 29 different genetic toxicity tests are summarized here. Different studies have been conducted including the bacterial reverse mutation assay (Ames Test), Aspergillus nidulans forward mutation assay, in-vitro cytogenetic assays in mammalian cell lines, UDS assays in mammalian and human cell lines and DNA binding studies. Positive and negative results depending on test system and conducting laboratory were found. The results are therefore ambiguous, following a conservative approach the substance can be regarded as positive for in vitro genotoxicity.

The DNA binding study was reported to be positive. For the other studies both positive and negative results have been found for 3-chloropropene with and without activation where results are usually more critical without activation. In general high concentrations are needed to elicit genotoxic effects.