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Key value for chemical safety assessment

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.