Registration Dossier
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EC number: 216-407-3 | CAS number: 1576-35-8
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Limited data is available for Toluene-4-sulphonohydrazide (T). The conclusion is therefore also based on read across to OBSH (S1).
Toluene-4-sulphonohydrazide was mutagenic in two reverse mutation assays (OECD 471) with Salmonella typhimurium and Escherichia coli with and wihtout S9 and in mouse lymphoma mutagenicity assay, but not did not induce chromosomal aberrations.
In summary, OBSH was shown to be mutagenic in two reliable reverse mutation assays (OECD 471) with Salmonella typhimurium and Escherichia coli with and wihtout S9.
Further a reliable a mammalian chromosome aberation test (OECD 473) was positive with and without S9 and also a hepatocyte DNA repair test was positive in rat as well as mouse heaptocytes.
In an in vivo OECD 474 OBSH did not induce micronuclei and chromosome aberations in mouse erythrocytes. Although no structural anomalies were found in this vivo test, OBSH with its reactive hydrazide structure most still be highly suspected to be a mutagen due to the clear positive in vitro tests showing direct mutagenic response, clastogenic repsonse and impact on DNA repair.
Based on this it is considered most appropriate to assign a classification with Muta 2 H341 to OBSH, as further more targeted in vivo testing on the direct mutagenic properties is considered superfluous as positive response is considered to be the most probable outcome.
Based on read-across to these data Toluene-4-sulphonohydrazide (T) should also be classified with Muta 2 H341, as well.
Link to relevant study records
- 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:
- Read-across from chromosome aberration study on one closely structural and physicochemical related substance: OBSH (4,4'-Oxybis (benzenesulfonyl hydrazide)).
For further read-across justification se document attached in section 13. - Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- other: CHL/IU cells
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- -S9: at 1360 µg/mL and above. +S9: at 696µg/mL and above
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity of OBSH was evaluated in an in vitro Mammalian chromosome aberration test with chinese hamster lung (CHL) cells. The study was performed in accordance with the OECD guideline 473. OBSH exhibited clastogenic activity on cultured Chinese Hamster Lung cells.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide the clastogenic potential may be considered relevant for this substances as well. - Executive summary:
No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity of OBSH was evaluated in an in vitro Mammalian chromosome aberration test with chinese hamster lung (CHL) cells. The study was performed in accordance with the OECD guideline 473. OBSH exhibited clastogenic activity on cultured Chinese Hamster Lung cells.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide theclastogenicpotential may be considered relevant for this substances as well.
See justification for read-across attached in section 13
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Read-across from Ames test studies on one closely structural and physicochemical related substance: OBSH (4,4'-Oxybis (benzenesulfonyl hydrazide)).
For further read-across justification se document attached in section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000µg/plate
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000µg/plate
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000µg/plate
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 300µg/plate
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Remarks on result:
- other: Study II
- Conclusions:
- No data is available for Toluene-4-sulphonohydrazide (T). The source substance OBSH demonstrated a mutagenic potential in both studies and therefore considered mutagenic in bacteria.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide the mutagenic potential may be considered relevant for this substances as well. - Executive summary:
No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity in vitro of OBSH was evaluation in two studies using bacterial reverse mutation assay. The studies were performed in accordance with the OECD guideline 471. In the first study OBSH showed mutagenic effects in Salmonella typhimurium TA 98, TA 100, and TA 1535 without metabolic activation and in Salmonella typhimurium TA 100 and TA 1535 with metabolic activation system. In the second study, OBSH showed mutagenic effects in Salmonella typhimurium TA 100, TA 1535, and WP2 uvrA without and with metabolic activation system.
Conclusively OBSH demonstrated a mutagenic potential in both studies and therefore considered mutagenic in bacteria.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide the mutagenic potential may be considered relevant for this substances as well.
See justification for read-across attached in section 13
- Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Read-across from DNA damage/repair study on one closely structural and physicochemical related substance: OBSH (4,4'-Oxybis (benzenesulfonyl hydrazide)).
For further read-across justification se document attached in section 13. - Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- hepatocytes:
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: strain/cell type: heaptocytes
- Conclusions:
- No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity of OBSH was evaluated in using a protocol similar with the OECD guideline 482. In the DNA repair test with rat hepatocytes OBSH elicited positive DNA repair synthesis and the nuclear grain counts were roughly related to the doses.
OBSH was positive in the DNA repair test with mouse hepatocytes.
The test substance was positive in the DNA repair test with hepatocytes of rat and mouse.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide it may a have a similar effects on DNA repair as well. - Executive summary:
No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity of OBSH was evaluated in using a protocol similar with the OECD guideline 482. In the DNA repair test with rat hepatocytes OBSH elicited positive DNA repair synthesis and the nuclear grain counts were roughly related to the doses.
OBSH was positive in the DNA repair test with mouse hepatocytes.
The test substance was positive in the DNA repair test with hepatocytes of rat and mouse.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide it may a have a similar effects on DNA repair as well.
See justification for read-across attached in section 13
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: This study was performed in accordance with the OECD guideline 471 and the GLP standard.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- Principles of method if other than guideline:
- NA
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- no data
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Details on mammalian cell type (if applicable):
- NA
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Male rat, liver, S9 mix induced with Aroclor 1254
- Test concentrations with justification for top dose:
- 11.1, 33.3, 100, 300, 1,000, and 3,000 µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data - Untreated negative controls:
- yes
- Remarks:
- solvent
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- other: 4-nitroquinoline and 2-aminoanthracene
- Details on test system and experimental conditions:
- Description of follow up repeat study: Dose range finding experiment was carried out using dose levels with 5-fold intervals of 1.6, 8, 40, 200, 1,000, and 5,000 µg/plate both in the absence and in the presence of metabolic activation system.
- Evaluation criteria:
- The number of revertant colonies increased significantly in at least one strain at one or more concentrations or the data set showed a dose related correlation.
- Statistics:
- no data
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000 µg/plate
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000 µg/plate
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 3000 µg/plate
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- above 300 µg/plate
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Additional information on results:
- none
- Conclusions:
- Interpretation of results (migrated information):
positive
OBSH showed mutagenic effects in Salmonella typhimurium TA 98, TA 100, and TA 1535 without metabolic activation and in Salmonella typhimurium TA 100 and TA 1535 with metabolic activation system. - Executive summary:
The genetic toxicity in vitro of OBSH was evaluation in a bacterial reverse mutation assay. The study was performed in accordance with the OECD guideline 471. OBSH showed mutagenic effects in Salmonella typhimurium TA 98, TA 100, and TA 1535 without metabolic activation and in Salmonella typhimurium TA 100 and TA 1535 with metabolic activation system.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed in accordance with the guidelines for screening mutagenicity testing of chemicals (chenical substances control law of Japan) and OECD TG 471. The study was performed in accordance with GLP standard.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- no data
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Details on mammalian cell type (if applicable):
- NA
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- male rat, liver, S9 mix induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- TA 100: 4.88, 9.77, 19.5, 39.1, 78.1, and 156 µg /plate (with and without S9 mix)
TA 1535: 0.61, 1.22, 2.44, 4.88, 9.77, and 19.5 µg/plate (with S9 mix)
Ta1535: 0.61, 1.22, 2.44, 4.88, 9.77, 19.5, 39.1 and 78.1 µg/plate (without S9 mix)
TA 98 and TA 1537: 313, 625, 1,250, 2,500, and 5,000 µg/plate (with and without S9 mix)
WP2 uvrA: 39.1, 78.1, 156, 313, 625, and 1,250 µg/plate (with and without S9 mix) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data - Untreated negative controls:
- yes
- Remarks:
- solvent
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 9-Aminoacridine hydrochloride, and 2-Aminoanthracene
- Details on test system and experimental conditions:
- Description of follow up repeat study: Concentration range finding experiment was carried out using concentration levels with 3-fold intervals of 2.29, 6.6, 20.6, 61.7, 185, 556, 1,667, and 5,000 µg/plate both in the absence and in the presence of metabolic activation system.
- Evaluation criteria:
- Criteria for determining a positive result is the number of revertant colonies increased double over in at least one strain at one or more concentrations and the data set showed a reproducible increase or a dose related correlation.
- Statistics:
- no data
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Additional information on results:
- CYTOTOXIC CONCENTRATION:
Without and with metabolic activation: not observed
GENOTOXIC EFFECT:
Without and with metabolic activation: positive in TA 100, TA 1535 and WP2 uvrA - Conclusions:
- Interpretation of results (migrated information):
positive
OBSH showed mutagenic effects in Salmonella typhimurium TA 100, TA 1535, and WP2 uvrA without and with metabolic activation system. - Executive summary:
The genetic toxicity in vitro of OBSH was evaluation in a bacterial reverse mutation assay.
The study was performed in accordance with the guideline for screening mutagenicity testing of chemicals (chenical substances control law of Japan) and the OECD guideline 471. OBSH showed mutagenic effects in Salmonella typhimurium TA 100, TA 1535, and WP2 uvrA without and with metabolic activation system.- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2001
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed in accordance with the OECD guideline 473, and in compliance with GLP standard.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- not specified
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Target gene:
- NA
- Species / strain / cell type:
- other: Chinese Hamster Lung (CHL/IU) Cells
- Details on mammalian cell type (if applicable):
- NA
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat, malem, liver, 30% S9 mix induced with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- Absence metabolic system; 0, 557, 696, 870, 1,088, 1,360, and 1,700 µg/mL
Presence metabolic system; 0, 357, 446, 557, 696, 870, and 1,088 µg/mL - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data - Untreated negative controls:
- yes
- Remarks:
- solvent
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- mitomycin C
- Details on test system and experimental conditions:
- Culture establishment: CHL cells in logarithmic were to maintain low aberration frequencies. Subcultured at low density, before over growth occurs. The cells were incubated at 37 C in atmosphere of 5 % (v/v) CO2 and 100 % humidity.
Description of follow up repeat study: Series of seven and ten concentration levels with 1.25-fold intervals were tested in the absence and the presence of metabolic activation system. - Evaluation criteria:
- The test was considered as positive in this assay if; 1) Statistically significant increase in the proportion of cells with structural aberrations (excluding gaps) occurs at one or more concentration levels 2) 1) exceed the normal range, 3) If the result of 1) is reproducible.
- Statistics:
- Fisher’s exact test and Chochran Armitage’s trend test (p-value: 0.05)
- Species / strain:
- other: Chinese Hamster Lung (CHL/IU) Cells
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- -S9: at 1360 µg/mL and above. +S9: at 696µg/mL and above
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- None
- Conclusions:
- Interpretation of results (migrated information):
positive
The genetic toxicity of OBSH was evaluated in an in vitro Mammalian chromosome aberration test on chinese hamster ling cells. The study was performed in accordance with the OECD guideline 473. OBSH exhibited clastogenic activity on cultured Chinese Hamster Lung cells. - Executive summary:
The genetic toxicity of OBSH was evaluated in an in vitro Mammalian chromosome aberration test on chinese hamster lung cells. The study was performed in accordance with the OECD guideline 473.
Significant dose-dependent increases in the proportion of cells with structural aberrations were observed in cultures both in the absence (557 to 870mg/mL) and presence (446 to 557mg/mL) metabolic activation system. Significant increases in the proportion of cells with numerical aberrations were not observed in cultures at all concentration levels.
In conclusion, OBSH exhibited clastogenic activity on cultured Chinese Hamster Lung cells both with and without S9.
- Endpoint:
- in vitro DNA damage and/or repair study
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Score evaluated in the OECD SIDS and considered to be well documented meeting generally scientific principles and acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Remarks:
- Study by OECD indicated to be well documented meeting generally scientific principles and acceptable for assessment
- Type of assay:
- DNA damage and repair assay, unscheduled DNA synthesis in mammalian cells in vitro
- Test concentrations with justification for top dose:
- 0.001; 0.0001; 0.00001 M
positive control: N-2-fluorenylacetamide in rat hepatocyte assay
positive control: 9,10.dimethyl-1,2-benz(a)anthracene in mouse hepatocyte assay - Vehicle / solvent:
- DMSO
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- yes
- Positive control substance:
- 9,10-dimethylbenzanthracene
- other: N-2-fluorenylacetamide
- Details on test system and experimental conditions:
- Hepatocytes were isolated from the livers of ACI/N rats weighing 200 ~ 250 g and C3H/HeN mice weighing about 20 g. The isolated hepatocytes were allowed to attach for 2 hr to plastic cover slips in primary culture using William Medium E. The culture were then washed and exposed to the test compounds and [Me-3H] thymidine for 20 hr.
- Solvent: Dimethyl sulfoxide
- Number of replicate: 2
- Positive control: N-2-fluorenylacetamide was used in the assay with rat hepatocytes, and 9,10-dimethyl-1,2-benz[a]anthracene was used in the assay with mouse hepatocytes.
- Description of follow up study: At the end of incubation, the cultures were washed in Williams’ Medium E, and the coverslips were mounted on glass slides. The slides were dipped in Sakura NR-M2 photographic emulsions and exposed for 14 days. Autoradiographic grains were counted on a CRT display with a microscopic attachment. - Evaluation criteria:
- Criteria for evaluating results: Each cell nucleus was considered positive when the net nuclear grain count was more than 5 grains above the cytoplasmic background. The test compounds were judged positive when the mean nuclear grain count was more than 5 grains or the positive cells were more than 33 %.
- Statistics:
- NA
- Species / strain:
- hepatocytes:
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- In the DNA repair test with rat hepatocytes, the test substance elicited positive DNA repair synthesis and the nuclear grain counts were roughly related to the doses. OBSH was positive in the DNA repair test with mouse hepatocytes.
The test substance was positive in the DNA repair test with hepatocytes of rat and mouse. - Remarks on result:
- other: strain/cell type: heaptocytes
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- In the DNA repair test with rat hepatocytes, the test substance elicited positive DNA repair synthesis and the nuclear grain counts were roughly related to the doses.
OBSH was positive in the DNA repair test with mouse hepatocytes.
The test substance was positive in the DNA repair test with hepatocytes of rat and mouse. - Executive summary:
OBSH was tested in a rat + mouse heaptocyte/ DNA repair test using concentrations of 0.001; 0.0001; 0.00001 M of OBSH in a vehicle of DMSO.
Positive control: N-2-fluorenylacetamide was used in the assay with rat hepatocytes, and 9,10-dimethyl-1,2-benz[a]anthracene was used in the assay with mouse hepatocytes.
In the DNA repair test with rat hepatocytes, the test substance elicited positive DNA repair synthesis and the nuclear grain counts were roughly related to the doses.
OBSH was positive in the DNA repair test with mouse hepatocytes.
The test substance was positive in the DNA repair test with hepatocytes of rat and mouse.
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1990
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- not specified
- Principles of method if other than guideline:
- NA
- GLP compliance:
- not specified
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- no data
- Species / strain / cell type:
- S. typhimurium TA 100
- Details on mammalian cell type (if applicable):
- NA
- Additional strain / cell type characteristics:
- not specified
- Metabolic activation:
- with and without
- Metabolic activation system:
- Liver S9 mix, male Sprague Dawley rats, induced with Aroclor 1254
- Test concentrations with justification for top dose:
- 100-10000 µg/plate
- Vehicle / solvent:
- No data
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Details on test system and experimental conditions:
- N/A
- Evaluation criteria:
- To be considered positive, it had to induce at least a doubling in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose
response to increasing concentrations of the test chemical. - Statistics:
- no data
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Remarks:
- at 100 µg/plate
- Cytotoxicity / choice of top concentrations:
- not specified
- Additional information on results:
- none
- Conclusions:
- p-toluenesulfonic hydrazide showed mutagenic effects in Salmonella typhimurium TA 100 at 100 µg/plate with and without metabolic activation system.
- Executive summary:
The genetic toxicity of p-toluenesulfonic hydrazide (p-TSH) was evaluation in a bacterial reverse mutation assay. The study was performed in equivalence to OECD guideline 471.
p-TSH showed mutagenic effects in Salmonella typhimurium TA 100 at 100 µg/plate with and without metabolic activation system.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium, other: TA 97, TA 98, TA 100, TA 102
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Trial 1: control (DSMO), 5, 10, 50, 100, 500, 100
Trial 2: control (Acetone), 7.5, 25, 75, 250, 750, 2500 - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used:
Trial 1: DMSO
Trial 2: acetone - Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- 2-acetylaminofluorene
- Species / strain:
- S. typhimurium, other: TA 97, TA98, TA 100, TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- In this study the mutagenic acitivity of TSH was determined in the salmonella/mammalian microsome assay. TSH induced gene mutations both with and without metabolic activation. This study indicates that TSH is mutagenic in vitro.
- Executive summary:
In this study the mutagenic acitivity of TSH was determined in the salmonella/mammalian microsome assay. TSH induced gene mutations both with and without metabolic activation. This study indicates that TSH is mutagenic in vitro.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254-induced rat liver homogenate (S9)
- Test concentrations with justification for top dose:
- Trial 1 (10 h): 0, 0.1, 0.3, 0.6, 1.0 mM
Trial 2 (16 h): 0, 0.1, 0.3, 0.6, 1.0 mM
The top dose was the highest dose, at which an adequate number of metaphase cells could be recovered - Vehicle / solvent:
- serum free complete medium
- Untreated negative controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- TSH does not induce chromosomal aberrations in CHO cells.
- Executive summary:
In this study the mutagenic acitivity of TSH was determined in the in vitro chromosomal aberration assay using Chinese hamster ovary (CHO) cells. TSH did not induce chromosomal aberrations in the CHO cells. In two seperate trials, there were no significant increase in the percentage of cells with chromosomal aberrations or the number of chromosomal aberrations per cell measured either 10 or 16 h following treatment. In all experiments, the top dose was the highest dose at which an adequate number of metaphase cells could be recovered. The results demonstrate that TSH does not induce chromosomal aberrations in CHO cells.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Type of assay:
- other: Mouse lymphoma mutagenicity assay
- Specific details on test material used for the study:
- No data
- Target gene:
- N/A
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- No data
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 miix, male rat liver, Aroclor 1254 induced
- Test concentrations with justification for top dose:
- 100-2400 µg/mL
- Vehicle / solvent:
- Not specified
- Untreated negative controls:
- not specified
- Negative solvent / vehicle controls:
- not specified
- True negative controls:
- not specified
- Positive controls:
- not specified
- Evaluation criteria:
- Mutant frequencies were expressed as mutants per 106 surviving cells. Although there are several different methods for evaluating mouse lymphoma data, results from this study were interpreted using a doubling of the mutant frequency over the concurrent solvent-treated control value as an indication of a positive effect, together with evidence of a dose-related increase. Only doses yielding total growth values of 10% were used in the analysis of induced mutant frequency. Doses yielding less than 10% total growth were used in determining dose response.
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Remarks:
- at 1000 µg/mL
- Cytotoxicity / choice of top concentrations:
- not specified
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- not determined
- Conclusions:
- p-toluenesulfonic hydrazide showed mutagenic effects in mouse lymphoma L5178Y at 1000 µg/mL without S9 metabolic activation system. The results were equivocal with S9 metabolic activation system
- Executive summary:
The genetic toxicity of p-toluenesulfonic hydrazide (p-TSH)was evaluation in a Mouse lymphoma mutagenicity assay. The study was performed in equivalence to OECD guideline 476.
p-TSH showed mutagenic effects in mouse lymphoma L5178Y at 1000 µg/mL without S9 metabolic activation system. The results were equivocal with S9 metabolic activation system.
Referenceopen allclose all
Table.Result of bacterial reverse mutation assay with4,4’-oxybis(benzenesulfonyl hydrazide)
Tester strain | Chemical treated | Dose (mg/plate) | Colonies/plate (mean±SD) | |
without S9 mix | with S9 mix | |||
TA 98 | Test item | 0 | 31±1 | 32±3 |
11.1 | 20±6 | 29±3 | ||
33.3 | 24±5 | 35±2 | ||
100 | 34±3 | 40±6 | ||
300 | 101±2 | 30±10 | ||
1,000 | 305±741 | 44±4 | ||
3,000 | 0±04 | 41±9 | ||
TA 100 | Test item | 0 | 100±16 | 113±0 |
11.1 | 189±83 | 169±16 | ||
33.3 | 219±7 | 269±12 | ||
100 | 315±13 | 439±18 | ||
300 | 349±1 | 438±68 | ||
1,000 | 302±12 | 318±8 | ||
3,000 | 0±04 | 349±8 | ||
TA 1535 | Test item | 0 | 10±0 | 8±4 |
11.1 | 73±8 | 120±10 | ||
33.3 | 118±3 | 295±13 | ||
100 | 243±2 | 437±61 | ||
300 | 187±20 | 320±61 | ||
1,000 | 12±32 | 259±15 | ||
3,000 | 0±04 | 449±47 | ||
TA 1537 | Test item | 0 | 14±3 | 16±1 |
11.1 | 24±2 | 13±4 | ||
33.3 | 18±1 | 17±1 | ||
100 | 12±6 | 17±0 | ||
300 | - 3 | 18±4 | ||
1,000 | - 3 | 24±1 | ||
3,000 | 0±04 | 16±4 | ||
E. coli WP2uvrA | Test item | 0 | 15±1 | 15±2 |
11.1 | 12±1 | 21±1 | ||
33.3 | 13±6 | 15±6 | ||
100 | 22±4 | 13±1 | ||
300 | 19±1 | 15±3 | ||
1,000 | 22±6 | 15±3 | ||
3,000 | 13±2 | 22±2 | ||
Positive control | ||||
TA 98 | 2-NF | 1.0 | 209±1 |
|
2-AA | 2.0 |
| 550±88 | |
TA 100 | SA | 0.5 | 502±62 |
|
2-AA | 2.0 |
| 699±13 | |
TA 1535 | SA | 0.5 | 251±24 |
|
2-AA | 5.0 |
| 131±9 | |
TA 1537 | 9-AA | 50.0 | 355±8 |
|
2-AA | 5.0 |
| 259±39 | |
WP2uvrA | 4-NQ | 2.0 | 926±86 |
|
2-AA | 10 |
| 297±115 | |
1;Colony counting and slight thin lawn, some very slight toxicity
2;Colony counting and thin lawn but microcolonies still evident
3;No colony count and thin lawn and probably macroscopic colonies grown from microcolonies
4;Complete killing
2-NF; 2-Nitrofluorene, 2-AA; 2-Aminoanthracene, SA; Sodium azide, 9-AA; 9-Aminoacridine, 4-NQ; 4-Nitroquinoline
Table1.Results of bacterial reverse assay of 4,4’-oxybis(benzenesulfonylhydrazide) [non-activation method: -S9mix]
Compound | Concentration (mg/plate) | Revertant coloniesperplate (Mean±S.D.) | ||||
TA 100 | TA1535 | WP2uvrA | TA98 | TA1537 | ||
DMSOa) | 0 | 115±17 | 14±0 | 15±6 | 27±6 | 6±1 |
Testsubstance | 2.44 |
| 21±3 |
|
|
|
4.88 | 143±12 | 35±4 |
|
|
| |
9.77 | 146±13 | 53±6 |
|
|
| |
19.5 | 191±15 | 89±10 |
|
|
| |
39.1 | 246±12 | 139±22 | 25±1 |
|
| |
78.1 | 327±18 | 209±22 | 21±7 |
|
| |
156 | 443±25 |
| 27±4 |
|
| |
313 |
|
| 62±5 | 32±2 | 7±1 | |
625 |
|
| 96±2 | 37±8 | 11±4 | |
1,250 |
|
| 124±5 | 36±4 | 6±3 | |
2,500+ |
|
|
| 44±14 | 11±2 | |
5,000+ |
|
|
| 38±3 | 14±5 | |
Positive control |
| 734±21b) | 459±3c) | 173±26b) | 644±8d) | 196±19e) |
a) Negative control (Dimethyl sulfoxide) b) AF-2; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, 0.01mg/plate c) NaN3;Sodium azide 0.5mg/plate d)AF-2, 0.1mg/plate e)9-AA; 9-Aminoacridinehydrochloride,80mg/plate
+: Visible precipitation was shown at the end of exposure period
Table2.Results of bacterial reverse assay of 4,4’-oxybis(benzenesulfonylhydrazide) [Activation method: +S9mix]
Compound | Concentration (mg/plate) | Revertant coloniesperplate (Mean±S.D.) | ||||
TA 100 | TA1535 | WP2uvrA | TA98 | TA1537 | ||
DMSOa) | 0 | 113±5 | 9±4 | 20±3 | 35±6 | 14±2 |
Testsubstance | 0.61 |
| 17±8 |
|
|
|
1.22 |
| 21±6 |
|
|
| |
2.44 |
| 30±3 |
|
|
| |
4.88 | 140±26 | 65±3 |
|
|
| |
9.77 | 173±21 | 105±1 |
|
|
| |
19.5 | 220±29 | 164±11 |
|
|
| |
39.1 | 283±20 |
| 22±5 |
|
| |
78.1 | 337±24 |
| 27±10 |
|
| |
156 | 385±25 |
| 32±4 |
|
| |
313 |
|
| 37±7 | 30±9 | 16±4 | |
625 |
|
| 63±6 | 31±6 | 13±5 | |
1,250 |
|
| 107±13 | 40±9 | 20±2 | |
2,500+ |
|
|
| 27±8 | 17±4 | |
5,000+ |
|
|
| 39±7 | 13±2 | |
Positive control |
| 920±13b) | 268±17c) | 659±61d) | 414±22e) | 149±19c) |
a) Negative control (Dimethyl sulfoxide)
b) 2-AA; 2-Aminoanthracene, 1mg/plate c) 2-AA, 1mg/plate d) 2-AA, 10mg/plate e) 2-AA, 0.5mg/plate
+: Visible precipitation was shown at the end of exposure period
Table 1. Chromosome aberration test on CHL cells treated with 4,4’-oxybis(benzenesulfonylhydrazide) [short-term treatment: -S9 mix]
Compound | Concentration (mg/mL) | Time of exposure (hr) | Relative cell growth (%) | No. of cells analyzed | No. of cells with aberrations –gap (%) | No. of cells analyzed for polyploid | No. of polyploid cells (%) | Final Judgment |
DMSOa) | 0 | 6 | 100.0 | 200 | 0 (0.0)# | 200 | 1 (0.5) |
|
Test substance | 557 | 6 | 47.7 | 200 | 8 (4.0)* | 200 | 1 (0.5) |
|
696 | 6 | 37.7 | 200 | 21 (10.5)* | 200 | 4 (2.0) |
| |
870 | 6 | 33.1 | 200 | 27 (13.5)* | 200 | 0 (0.0) | Positive | |
1088 | 6 | 18.0 | 200 | 6 (3.0)* | 200 | 2 (1.0) |
| |
1360c) | 6 | 9.1 | Toxic |
|
|
|
| |
1700c) | 6 | 3.0 | Toxic |
|
|
|
| |
MMCb) | 0.1 | 6 | 57.2 | 200 | 88 (44.0)* | 200 | 0 (0.0) | Positive |
-gap: total number of cells with aberrations except gap
# p≤0.05: Significant difference by trend test (Cochran-Armitage trend test)
* p≤0.05: Significant difference from the negative control group (Fisher’s exact test)
a) Negative control (Dimethyl sulfoxide), b) Positive control (Mitomycin C)
c) Visible precipitation was shown at the end of exposure period
Table 2. Chromosome aberration test on CHL cells treated with 4,4’-oxybis(benzenesulfonylhydrazide) [short-term treatment: +S9 mix]
Compound | Concentration (mg/mL) | Time of exposure (hr) | Relative cell growth (%) | No. of cells analyzed | No. of cells with aberrations –gap (%) | No. of cells analyzed for polyploid | No. of polyploid cells (%) | Final Judgment |
DMSOa) | 0 | 6 | 100.0 | 200 | 0 (0.0)# | 200 | 2(1.0) |
|
Test substance | 357 | 6 | 58.7 | 200 | 3 (1.5)* | 200 | 3(1.5) |
|
446 | 6 | 46.9 | 200 | 6 (3.0)* | 200 | 2(1.0) |
| |
557 | 6 | 18.2 | 200 | 29 (14.5)* | 200 | 0(0.0) | Positive | |
696 | 6 | 4.8 | Toxic |
|
|
|
| |
870 | 6 | 3.3 | Toxic |
|
|
|
| |
1088 | 6 | 2.4 | Toxic |
|
|
|
| |
CPb) | 12.5 | 6 | 85.4 | 200 | 66 (33.0)* | 200 | 1(0.5) | Positive |
-gap: total number of cells with aberrations except gap
# p≤0.05: Significant difference by trend test (Cochran-Armitage trend test)
* p≤0.05: Significant difference from the negative control group (Fisher’s exact test)
a) Negative control (Dimethyl sulfoxide), b) Positive control (Cyclophosphamide)
In two seperate trials, there were no significant increase in the percentage of cells with chromosomal aberrations or the number of chromosomal aberrations per cell measured either 10 or 16 h following treatment. In all experiments, the top dose was the highest dose at which an adequate number of metaphase cells could be recovered
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (positive)
Genetic toxicity in vivo
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed in accordance with the OECD guideline 474, and in compliace with GLP standard.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- not specified
- Principles of method if other than guideline:
- NA
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- ICR
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: 8 weeks
- Weight at study initiation: 28.5 - 36.0 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
no data
IN-LIFE DATES: no data - Route of administration:
- intraperitoneal
- Vehicle:
- - Vehicle(s)/solvent(s) used: MC (methyl cellulose)
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: no data
- Amount of vehicle (if gavage or dermal): 0.5% MC
- Type and concentration of dispersant aid (if powder): no data
- Lot/batch no. (if required): 126H0394
- Purity: no data - Details on exposure:
- no data
- Duration of treatment / exposure:
- two treatments at 24 hour intervals
- Frequency of treatment:
- duplicate treatments (positive control group was dosed once)
- Post exposure period:
- 24 hours
- Remarks:
- Doses / Concentrations:
0, 375, 750 and 1500 mg/kg bw/day
Basis: - No. of animals per sex per dose:
- 6
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide.H2O
- Justification for choice of positive control(s): no data
- Route of administration: intraperitoneal injection
- Doses / concentrations: 70mg/kg - Tissues and cell types examined:
- erythrocytes
- Details of tissue and slide preparation:
- no data
- Evaluation criteria:
- At least 2,000 polychromatic erythrocytes per animals were scored for the incidence of micronuclei.
There are several criteria for determining a positive result, such as a dose-related increase in the number of micronucleated cells or a clear increase in the number of micronucleated cells in a single dose group at a single sampling time. - Statistics:
- To compare the results of the control and treatment groups, Kruskal-Wallis’ H-test was carried out. If this result was significant, Dunnett’s t-test was conducted to find out significance. If there was a significant difference, Cochran-Armitage trend test was conducted to confirm the dose-dependency. Mann-Whitney’s U-test was carried out to compare the results of the control and positive controls.
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.
- Conclusions:
- Interpretation of results (migrated information): negative
The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474. It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells. - Executive summary:
The genetic toxicity in vivo of OBSH was evaluated in a Mammalian erythrocyte micronucleus test. The test was performed in accordance with the OECD guideline 474.
All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.
It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- Read-across from micronucleus study on one closely structural and physicochemical related substance: OBSH (4,4'-Oxybis (benzenesulfonyl hydrazide)).
For further read-across justification se document attached in section 13. - Reason / purpose for cross-reference:
- read-across source
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- not examined
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Executive summary:
No data is available for Toluene-4-sulphonohydrazide (T).
The genetic toxicity in vivo of OBSH was evaluated in accordance with the OECD guideline 474 in a Mammalian erythrocyte micronucleus test.
All animals dosed with OBSH exhibited similar PCE/(PCE + NCE) ratios and MNPCE frequencies compared to those of negative control animals (p > 0.01). All frequencies of MNPCE in the negative control groups fell within acceptable ranges, while the positive control groups induced clear increase in the frequencies of MNPCE.
It was concluded that OBSH did not induce micronuclei in the mice bone marrow cells.
Due to the close chemical similarity to Toluene-4-sulphonohydrazide this value may be considered relevant for this substances as well.
See justification for read-across attached in section 13.
Referenceopen allclose all
Table. Summary of PCE/(PCE+NCE) ratio and MNPCE frequency
Treatment group | Dose (mg/kg) | No. of Animal | PCE/(PCE+NCE) (mean±S.D.) | MNPCE per2,000 PCE (mean±S.D.) |
Vehicle(0.5 % methyl cellulose) | 0 | 6 | 0.43 ( 0.11 | 0.67 ( 0.82 |
OBSH | 375 | 6 | 0.47 ( 0.04 | 0.67 ( 0.82 |
| 750 | 6 | 0.47 ( 0.05 | 1.00 ( 0.89 |
| 1,500 | 6 | 0.45 ( 0.03 | 1.33 ( 0.82 |
Cyclophosphamide | 70 | 6 | 0.37( 0.04 | 75.50 ( 22.41* |
*: Significant difference from the control at p < 0.01
MNPCE; Micronucleated polychromatic erythrocyte,
PCE; Polychromatic erythrocyte,
NCE; Normochromatic erythrocyte,Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
OBSH was shown to be mutagenic in two reliable reverse mutation assays (OECD 471) with Salmonella typhimurium and Escherichia coli with and wihtout S9.
Further a reliable a mammalian chromosome aberation test (OECD 473) was positive with and without S9 and further a hepatocyte DNA repair test was positive in rat as well as mouse heaptocytes.
The genetic toxicity of OBSH in vivo was evaluated in a mammalian erythrocyte micronucleus test (OECD 474). It was concluded that OBSH did not induce micronuclei in mouse erythrocytes (negative).
Although no structural anomalies were found in this vivo test OBSH must be suspeced to be a mutagen due to the clear positive in vitro tests showing direct mutagenic response, clastogenic response and response on DNA repair.
Hence
Short description of key information:
In in vitro bacterial reverse mutation tests (OECD TG 471), OBSH showed positive results in Salmonella typhimurium strains TA 98, TA 100, TA 1535 and/or Escherichia coli (WP2 uvrA) with or without S9 mix. In a chromosomal aberration test (OECD TG 473) with CHL cells and in a DNA repair test with rat and mouse hepatocytes, OBSH elicited positive results. However, in an in vivo mammalian erythrocyte micronucleus assay (OECD TG 474), OBSH did not exhibit mutagenic effects in mouse bone marrow cells at doses ranging from 375 to 1,500 mg/kg bw.
Endpoint Conclusion: Adverse effect observed (positive)
Justification for classification or non-classification
In summary, OBSH was shown to be mutagenic in two reliable reverse mutation assays (OECD 471) with Salmonella typhimurium and Escherichia coli with and wihtout S9.
Further a reliable a mammalian chromosome aberation test (OECD 473) was positive with and without S9 and also a hepatocyte DNA repair test was positive in rat as well as mouse heaptocytes.
In an in vivo OECD 474 OBSH did not induce micronuclei and chromosome aberations in mouse erythrocytes. Although no structural anomalies were found in this vivo test, OBSH with its reactive hydrazide structure most still be highly suspected to be a mutagen due to the clear positive in vitro tests showing direct mutagenic response, clastogenic repsonse and impact on DNA repair.
Based on this it is considered most appropriate to assign a classification with Muta 2 H341 to OBSH (S1), as further more targeted in vivo testing on the direct mutagenic properties is considered superfluous as positive response is considered to be the most probable outcome.
Based on read-across to these data Toluene-4-sulphonohydrazide (T) should also be classified with Muta 2 H341, as well.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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