2-chloroethanol

Endpoint summary

Additional information

For the genetic toxicity in vitro the following studies were identified, briefly summarised below:

Flag	Author	Year	Test	R	Conclusion
Key	JETOC	1996	Ames	2	Weak positive results only at a dose level of 5 mg/plate (limit concentration) which are not reproducible in independent experiments.
Key	Haworth	1983	Ames	2	Weak positive at high concentrations near or above the limit dose recommended in OECD Guideline 471.
Sup	Nakamura	1979	Ames	2	In the Ames test only at extremely high dose levels an increase in the number of revertants was found in TA1535 with metabolic activation.
Sup	Elmore	1976	Ames	4	At dose levels up to 80 µg/ml no mutagenic effects were found without metabolic activation in S. typhimurium TA1535, TA100, TA1537, TA1538, and TA98.
Sup	Bartsch	1975	Ames	2	Increase in revertants only at high dose levels > 5 mg/plate in S. typhimurium TA1530.
Sup	Bignami	1980	Ames	2	Positive results in S. typhimurium TA1535 at extremely high concentrations.
Sup	Malaveille	1975	Ames	2	Mutagenic effects in S. typhimurium TA1530 at a dose level of 3.2 mg/ml with and without metabolic activation.
Sup	McCann	1975	Ames	2	In the Ames test no mutagenic activity was found in TA100 and TA1535 at concentrations up to 5 mg/plate with and without metabolic activation.
Sup	Stolzenberg	1980	Ames	2	In the Ames test only weak mutagenic activity was found in TA100 at a concentrations of 8 mg/plate with and without metabolic activation.
Sup	Min	1987	Ames	2	In the Ames test in S. typhimurium TA98 and TA100 weak positive effects were found with and without metabolic activation at extremely high dose levels.
Sup	Rosenkranz	74a/77	Ames	2	In the Ames test in S. typhimurium TA1530 weak mutagenic effects were found without metabolic activation at high dose levels.
Sup	Rosenkranz	74b/77	Ames	2	In the Ames test in S. typhimurium TA1530 & 1535 mutagenic effects were found without metabolic activation at high dose levels > the recommended max. concentration of 5 mg/plate.
Sup	Rannug	1976	Ames	2	No mutagenic effects in S. typhimurium TA1535 without metabolic activation even at extremely high doses (80 mg/ml).
Sup	Norpoth	1980	Ames	4	Using one dose level negative results were obtained in the Ames test with S. typhimurium TA98 and E. coli WP2uvrA.
Sup	Pfeiffer	1980	Ames	3	In the Ames test positive results were obtained in S. typhimurium TA100 & TA1535 but no final evaluation is possible without data on concurrent controls.
Sup	Loefroth	1978	Ames	2	In the Ames test a weak positive result was found in S. typhimurium TA100 with metabolic activation at extremely high dose levels.
Sup	Kharchenikova	1997	Ames	4	In the Ames test mutagenic effects were recorded in S. typhimurium TA100 with and without metabolic activation only at extremely high dose levels.
Sup	Laumbach	1977	Ames	4	No mutagenic effects in the Ames test without metabolic activation using the S. typhimurium strains TA98, TA100, TA1535, TA1537, TA1538.
Sup	Voogd	1972	Bac gen mutat	2	Induction of gene mutation in bacteria without metabolic activation at high concentrations in the Fluctuation test.
Sup	Bignami	1980	Bac gen mutat	2	In Streptomyces coelicolor no reverse mutation was noted even at very high dose levels.
Sup	Knaap	1982	Bac gen mutat	2	Dose dependent mutagenic effects in Klebsiella pneumoniae using a forward mutation assay.
Sup	Elmore	1976	Bac DNA damage	2	In a modified rec-assay no DNA damage was detected in Bacillus subtilis.
Sup	Laumbach	1977	Bac DNA damage	2	No DNA damage was detected in the modified rec-assay.
Sup	Rosenkranz	74/77	Bac DNA damage	2	DNA repair deficient E. coli revealed an increased inhibition compared to the proficient strain indicating DNA damage.
Sup	DeMartini	1992	Bac DNA damage	2	Positive results in the Microscreen prophage-induction assay in E. coli without metabolic activation and weak positive results with metabolic activation.
Key	Loprieno	1977	Mitotic recom yeast	2	In a study on mitotic recombination in Saccharomyces cerevisiae D4 negative results were obtained with and without metabolic activation at cytotoxic dose levels.
Sup	Crebelli	1984	Mitotic recom yeast	2	In Aspergillus nidulans somatic segregation was induced without metabolic activation at a high dose level of 6 mg/ml.
Key	Loprieno	1977	Gene mutat yeast	2	In a study on forward mutation in Schizosaccharomyces pombe P1 negative results were obtained with and without metabolic activation at cytotoxic dose levels.
Sup	Bignami	1980	Gene mutat yeast	2	Ambiguous test results in forward gene mutatation assays in Aspergillus nidulans at very high dose levels.
Key	Ivett	1989	Cytogenetic	2	In CHO cells the test substance was mutagenic in the chromosome aberration assay with metabolic activation at cytotoxic concentrations.
Key	JETOC	1996	Cytogenetic	2	In CHL cells no increase in chromosome aberration was detected without metabolic activation at dose levels up to 5 mg/ml (limit dose).
Key	McGregor	86/88	Mouse lymphoma	2	In the mouse lymphoma assay 2-chloroethanol induced with metabolic activation a dose dependent reproducible increase in mutations also at concentrations without cytotoxic effects.
Sup	Brown	1979	Mouse lymphoma	4	Mutagenic effects in the mouse lymphoma assay without metabolic activation.
Sup	Hubermann	1975	HPRT	2	In the HPRT assay no mutagenic activity was found without metabolic activation at dose levels < 2.5 mM (200 µg/ml).
Sup	Knaap	1982	HPRT	2	In the HPRT assay in mouse lymphoma cells no mutagenic effects were detected without metabolic activation even at dose levels above the recommended limit dose.
Sup	Stankowski	1988	HPRT	4	No gene mutagenic effects in the HPRT assay in CHO cells with and without metabolic activation.
Sup	Flowers	1988	HPRT	4	Gene mutagenic effects in the HPRT assay in CHO cells in the presence of metabolic activation but negative results without metabolic activation.
Sup	Stankowski	1988	XPRT	4	Presumably no gene mutagenic effects in the XPRT assay in AS52 cells without metabolic activation and non-reproducible weak positive results with metabolic activation.
Sup	Huberman	1975	ATPase assay	2	In the Na+/K+ ATPase assay no mutagenic activity was found without metabolic activation at dose levels < 2.5 mM (200 µg/ml).
Key	Ivett	1989	SCE assay	2	An increased incidence in sister chromatid exchange in CHO cells with and without metabolic activation was reported; higher genotoxic activity was seen with metabolic activation.
Sup	Stich	1981	UDS test	4	Induction of unscheduled DNA synthesis in mammalian fibroblast.
Sup	Brambilla	1992	UDS test	4	No increases in UDS of exposed hepatocytes were detected at the max. non-cytotoxic concentration.
Sup	Allavena	1992	UDS test	2	In the UDS assay no genotoxic activity was found in rat hepatocytes exposed for 20 h to concentrations up to the cytotoxicity threshold.
Sup	Allavena	1992	Alkaline elution Assay	2	In the alkaline elution assay no genotoxic activity was found in rat hepatocytes exposed for 20 h to concentrations up to the cytotoxicity threshold.
Sup	Painter	1982	DNA synth inhib	2	No inhibition of DNA synthesis (indicating no DNA damage) was detected in HeLa cells after exposure to the test substance with and without metabolic activation.
Sup	Matthews	1993	Cell transformation	2	In the cell transformation assay in BALB/c-3T3 cells without metabolic activation positive results were reported even at non-cytotoxic concentrations.
Sup	Kajiwara	1997	Cell transformation	2	In the cell transformation assay in BALB/c-3T3 cells tested without metabolic activation negative results were reported even at cytotoxic concentrations and dose levels up to 5 mg/ml.

R: Reliability

Overall summary:

Ames test: in most assays positive

Bac gen mutat: equivocal

Bac DNA damage: equivocal

Mitotic recom/Gene mutat yeast: Key studies negative

Cytogenetic: equivocal

ATPase assay: negative

SCE assay: positive

UDS test: in most assays negative

Alkaline elution assay: negative

Mouse lymphoma: positive

HPRT/XPRT: in most assays negative

DNA synth inhib: negative

Cell transformation: equivocal

Conclusion:

The available in vitro data demonstrated equivocal results. Thus, it is not possible to conclude finally on the in vitro genotoxic potential of 2 -chloroethanol.

For the genetic toxicity in vivo the following studies were identified and briefly summarised:

Purpose Flag	Author	Year	Test	R	Conclusion
Key	Shelby	1993	mouse micronucleus	2	In the mouse bone marrow micronucleus assay no mutagenic activity was detected at dose levels reaching toxicity threshold.
Sup	Allavena	1992	rat micronucleus	2	Male rats gavaged once or twice with 45 mg/kg bw did not show clastogenic effects in the liver or bone marrow.
Sup	Conan	1979	mouse micronucleus	3	In the mouse bone marrow micronucleus assay oral doses of up to 120 mg/kg bw did not induce clastogenic effects,however, the study is of limited validity.
Sup	Shelby	1995	mouse micronucleus	4	In an insufficiently documented mouse bone marrow micronucleus assay no mutagenic activity was detected at dose levels reaching toxicity threshold.
Sup	Shelby	1995	mouse cytogenetic	4	In an insufficiently documented chromosome aberration assay in mice no mutagenic activity was found at dose levels up to the toxicity threshold.
Sup	Semenova	1977	rat cytogenetic	4	Clastogenic effects were reported in a Russian bone marrow cytogenetic study in rats after repeated inhalation or oral exposure, however, the validity of these results is questionable.
Key	Epstein	1972	mouse Dominant Lethal	2	In the mouse dominant lethal assay no mutagenic effects were detected at dose levels up to 130 mg/kg bw/day.
Key	FDA/Sheu	1980/1983	mouse heritable transl.	2	In the mouse heritable translocation assay i.p. injection of doses up to 60 mg/kg bw/day for 5 weeks did not induce structural or numerical chromosome aberrations.
Sup	Allavena	1992	rat UPS assay	2	Isolated hepatocytes of male rats gavaged once or twice with 45 mg/lcg bw did not show genotoxic effects measured by the UDS assay.
Sup	Storer	1985	mouse alkaline elution	2	No SingleStrandbreaksandno alkaline labile site were found in hepatic DNA of mice using the alkaline / elution technique 4 h after single i.p. injection of dosesupto 96 mg/kg bw (hepatoxic dose level).
Sup	Allavena	1992	rat alkaline elution	2	Isolated hepatocytes of male rats gavaged once or twice with 45 mg/kg bw did not show genotoxic effects measured by the alkaline elution assay.
Sup	Kitchin	1993	rat alkaline elution	2	In female rats treated twice via gavage with doses up to 54 mg/kg bw no DNA damage was detected in the alkaline elution assay.
Key	Knaap	1982	Drosophila	2	In the SLRL assay in Drosophila no gene mutagenic activity on male germ cells was detected.
Sup	NTP, 495716	1986-1990	SCE	2	In the sister chromatid exchange assay negative results were observed in concentrations of 18.75, 37.5 and 75 mg/kg bw.
Sup	Valencia	1985	Drosophila	2	No gene mutation was induced in the Drosophila SLRL test after 4 h inhalation to 400 ppm.
Non	Isakova	1971	Cytogengetic	3	Retarded chromosomses in the bone marrow, increase in the number of chromosomal aberrations (Breakage) were observed. The result is however invalid, respectively (creteria making the stuty invalid see above).

 

Summary: 14 out of 16 studies demonstrated negative results for the genotoxicity of 2 -chloroethanol. In two cytogenetic studies in rats an increased number of chromosomal abberation was mentioned. The validity of the results of the two cytogenetic studies were however questionable. Conclusion: Based on the available data 2 -chloroethanol does not cause genotoxic effects in vivo. Overall conclusion: The results obtained with 2 -chloroethanol in a variety of in vitro test systems for genotoxicity were inconsistent. In contrast, the available in vivo studies provided no evidence of genotoxic effects for 2 -chloroethanol. Thus, it is concluded that 2 -chloroethanol is not genotoxic.

Short description of key information:
2 -chloroethanol is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, the test item is not subject to C&L according to Directive 67/548/EEC or the Regulation 1272/2008/EC.