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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro:

- Ames test (OECD 471): negative (CIT, 1993)
- Mammalian cell gene mutation test (similar to OECD 476): negative (PPC/SIDS, 1982)
- Mammalian cytogenetic test (OECD 473): negative (CIT, 1996)


In vivo:
- Mammalian micronucleus test (OECD 474): negative (BASF/CIT, 2002)

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
26th of may 1983 and Draft Proposal of 1991
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
- Name of the test item (as cited by study report): 2-mercaptoethanol, sodium salt
- Purity: 45.21%
- Batch No.: 927056
- Appearance: Yellow, liquid
Target gene:
his
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat liver S-9 mix
Test concentrations with justification for top dose:
0, 125, 250, 1000, 2000 ug/plate. The highest concentration (2000 µg/plate) showing moderate toxicity: decreased by approximately 50% of the number of revertant.
Vehicle / solvent:
Distilled water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
mitomycin C
other: 2-anthramine (2AM) and danthron (DTH)
Details on test system and experimental conditions:
- Preincubation method : the test substance solution (maximum volume: 0.1 ml), 0.5 ml of S9 mix and 0.1 mL of the strain were incubated for 60 minutes at 37°C prior adding the overlay agar and pouring onto the surface of a minimum agar plate.
- Direct plate incorporation method: the test substance solution (maximum volume: 0.1 ml), 0.5 mL of S9 mix (when required) and 0 .1 mL of the strain were added to 2 mL molten agar containing traces of histidine and biotin and maintained at +45°C. After rapid homogenization, the mixture was spread out on a Petri plate containing minimum medium.
- The methods used were the direct plate incorporation method (both tests without S9 mix, first test with S9 mix) or the preincubation method (second test with S9 mix) described by Maron and Ames.
Evaluation criteria:
The following criteria were used as an aid for determining a positive response: a reproducible and significant dose relationship using a linear regression analysis, considered as significant if p<0 .05 (for n = 18 values, the correlation coefficient must be r >0 .47) and/or a reproducible and significant increase (i.e. a doubling in the number of revertants for at least one of the tested strains when compared to that of the negative and/or solvent controls) for at least one of the tested concentrations.
A test substance is considered as non-mutagenic in this test system if the above two criteria are not fully met. Biological and statistical significances were considered during the evaluation.
Key result
Species / strain:
S. typhimurium, other: TA98, TA100, TA102, TA1535, TA1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: see additional information on results
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
CYTOTOXICITY IN PRELIMINARY TEST
- Without metabolic activation moderate effects on bacterial lawn at 2260 ug/plate, slight effects at 1130 ug/plate; number of revertants decreased to ca. 50% of solvent control at 1130 ug/plate and ca. 7% at 2260 ug/plate
- With metabolic activation no effects on bacterial lawn but decrease in the number of revertants at 452 and 1130 μg/plate (ca. 50% of solvent control), at 2260 μg/plate ca. 7%.

GENOTOXIC EFFECTS IN THE MAIN STUDY
- The test substance 2-Mercaptoethanol, sodium salt did not induce any significant increase in the number of revertants, with or without S9 mix, in any of the 5 strains tested.
- Negative and positive controls were valid.
- The high dose level decreased the number of revertants to ca. 50% of the solvent control in TA100 and TA102 (with and without MA), to ca. 70% in TA98 and TA1537 (with and without MA) in at least one out of 2 trials.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Additional information is available in the endpoint summaries and the read-across justification (see section 13).
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
lymphocytes: human
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Result read-across source CAS No. 60-24-2
Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Additional information is available in the endpoint summaries and the read-across justification (see section 13).
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: Result read-across source CAS No. 60-24-2
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

In vitro:

In a study conducted according to the OECD TG 471 guidelines (SNEA, 1993) sodium 2-mercaptoethanolate did not induce reverse gene mutations in Salmonella typhimurium strains TA 98, TA 100, TA 102, TA 1535, and TA 1537 in the presence or absence of metabolic activation when tested up to cytotoxic concentrations (concentrations 125, 250, 1000, 2000 µg/plate).

Read across: 2 -Mercaptoethanol

No other studies regarding the genetic toxicity of sodium 2 -mercaptoethanolate were available. Therefore, data on the structural analogue 2 -mercaptoethanol (CAS: 60 -24 -2) has been used.

In vitro

Negative results with and without metabolic activation were also reported in mouse lymphoma L5178Y cells (similar to OECD 476) (Phillips Petroleum Company, 1982). In this test, concentrations used were 80, 120, 170, 240, 340, 500, 700 and 1000 µg/mL. In an in vitro chromosomal aberration test conducted according to the OECD TG 473 and following GLP, human lymphocytes were exposed to concentrations of 30, 100, 300, 1000, 3000 and 5000 µg/mL test substance. (CIT, 1996) Under the experimental conditions, 2-mercaptoethanol was negative with and without metabolic activation.

 

In vivo:

In a micronucleus assay according to the OECD TG 474 and following GLP, male and female mice were treated intraperitoneally with 50, 100, or 200 mg/kg bw 2-mercaptoethanol. Males of the high dose group showed a slight but statistically significant increase in the frequency of MPE; but data generated in the additional analysis (further 2000 polychromatic erythrocytes per animal evaluated) showed that there was no significant difference between males of the high dose group and the corresponding control. In none of the other treatment groups the number of micronucleated cells was significantly elevated. The high dose resulted in clinical signs of toxicity. In male mice of the mid and high dose group the ratio of polychromatic erythrocytes to normochromatic erythrocytes was significantly decreased indicating toxic effects in the bone marrow. Under the condition of this study the test substance did not induce damage to the chromosomes or the mitotic apparatus of mouse bone marrow cells (BASF, 2002).

Justification for classification or non-classification

Based on the available data, the substance is not classified for genetic toxicity according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.