6-deoxy-L-mannose

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In Vitro (Mutagenic effects - bacterial): QSAR; Bacterial reverse mutation assay. Negative. Reliability = 2.

In Vitro (Clastogenic effects - mammalian): QSAR; Chromosome aberrations. Negative. Reliability = 2.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline available

Principles of method if other than guideline:

Times v.2.27.17.6 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC{P+}(O)C{P+}(O)C{P-}(O)C{P-}(O)C=O

Key result

Species / strain:

S. typhimurium, other:

Metabolic activation:

with

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Negative with metabolic activation

Executive summary:

The Times model for in vitro bacterial cell mutagenicity was used within the QSAR Toolbox. The prediction was negative with activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline available

Principles of method if other than guideline:

Times v.2.27.17.6 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC{P+}(O)C{P+}(O)C{P-}(O)C{P-}(O)C=O

Key result

Species / strain:

S. typhimurium, other:

Metabolic activation:

without

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Negative without metabolic activation

Executive summary:

The Times model for in vitro bacterial cell mutagenicity was used within the QSAR Toolbox. The prediction was negative without activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline available

Principles of method if other than guideline:

Times v.2.27.17.6 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC{P+}(O)C{P+}(O)C{P-}(O)C{P-}(O)C=O

Key result

Species / strain:

other: CHO and CHL cells

Metabolic activation:

with

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Negative with metabolic activation

Executive summary:

The Times model for in vitro chromosome aberrations was used within the QSAR Toolbox. The prediction was negative with activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 4

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline available

Principles of method if other than guideline:

Times v.2.27.17.6 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID.

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC{P+}(O)C{P+}(O)C{P-}(O)C{P-}(O)C=O

Key result

Species / strain:

other: CHO and CHL cells

Metabolic activation:

without

Genotoxicity:

negative

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Negative without metabolic activation

Executive summary:

The Times model for in vitro chromosome aberrations was used within the QSAR Toolbox. The prediction was negative without activation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 5

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

This study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions). Otherwise the study has a reliability of 1 (reliable without restriction).

Justification for type of information:

Additional documentation, provided within the IUCLID Assessment Reports (Section 13), supports the read-across approach.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

Initial toxicity-mutation assay: 1.5, 5.0, 15, 50, 150, 500, 1500, 5000 µg/plate
Confirmatory mutagenicity assay: 50, 150, 500, 1500, 5000 µg/plate

Vehicle / solvent:

Water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

no

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

methylmethanesulfonate

other: 2-aminoanthracene

Details on test system and experimental conditions:

The BRMA assay was conducted using the plate incorporation method.

Statistics:

Not reported

Key result

Species / strain:

S. typhimurium TA 1535

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

Key result

Species / strain:

S. typhimurium TA 1537

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

Key result

Species / strain:

S. typhimurium TA 98

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

Key result

Species / strain:

S. typhimurium TA 100

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

Key result

Species / strain:

E. coli WP2 uvr A

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

Additional information on results:

Neither precipitate nor toxicity was observed. Treatment with the positive control agents resulted in significant increases in the number of revertant colonies. All negative and positive control results were within the range of historical values.

 

Concentration (µg/plate)	Revertant colonies per plate (mean ± standard deviation)
	TA98		TA100		TA1535		TA1537		WPuvrA
	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9
Initial toxicity-mutation assay
Negative control (water)	23 ± 1	39 ± 6	117 ± 13	142 ± 5	17 ± 3	12 ± 4	7 ± 4	6 ± 0	29 ± 3	40 ± 17
1.5	16±3	30± 5	101± 14	120± 4	115± 3	17± 4	5± 1	7± 3	31± 9	34± 1
5.0	22± 2	30± 10	118± 17	121± 6	12± 4	14± 5	6± 3	6± 4	30± 9	34± 6
15	27± 1	30± 16	110± 17	129± 13	14± 4	18± 1	9± 6	6± 6	36± 7	37± 8
50	25± 4	28± 2	114± 30	126± 7	16± 2	15± 1	5± 1	5± 1	36± 3	31± 7
150	17± 2	25± 1	113± 8	128± 10	16± 6	12± 3	5± 1	2± 1	31± 3	27± 1
500	24± 6	26± 3	119± 15	113± 16	11± 3	11± 0	7± 5	5± 0	25± 2	39± 3
1500	20± 4	28± 7	112± 5	105± 5	10± 1	11± 3	2± 1	4± 4	31± 4	41± 6
5000	18± 6	34± 1	123± 14	121± 27	15± 1	12± 5	5± 5	6± 4	30± 10	39± 23
Positive control^a,b	191± 17	256± 20	568± 15	432± 25	444± 62	57± 7	322± 187	32± 4	197± 14	294± 28
Confirmatory mutagenicity assay
Negative control (water)	20± 6	20± 2	106± 17	114± 3	17± 4	10± 2	3± 1	4± 1	32± 3	34± 7
50	17± 3	14± 7	119± 8	110± 9	10± 4	8± 3	5± 5	4± 3	37± 14	32± 1
150	22± 6	21± 6	115± 8	134± 5	21± 4	9± 4	7± 3	6± 2	33± 6	28± 5
500	13± 7	12± 7	122± 14	133± 13	13± 2	12± 3	6± 2	5± 1	34± 3	34± 2
1500	17± 4	15± 4	116± 7	134± 9	12± 2	9± 2	3± 1	8± 2	23± 8	32± 5
5000	19± 5	14± 5	93± 8	108± 7	11± 2	12± 7	5± 4	7± 4	24± 4	29± 2
Positive control^a,b	129± 37	477± 51	628± 85	848± 45	532± 31	96± 30	168± 47	17± 3	345± 29	258± 23
^aPostivie controls -S9: TA98 = 1.0 µg/plate 2-NF; TA100 and TA1535 1.0 µg/plate naN3; TA1537 = 75 µg/plate 9-AA; WP2uvrA = 1000 µg/plate MMS. ^bPositive controls +S9: TA98, TA1535, and TA1537 = 1.0 µg/plate 2-AA; Ta100 = 2.0 µg/plate 2-AA; WP2uvrA = 15 µg/plate 2-AA

 

Conclusions:

Negative with and without activation

Executive summary:

A bacterial reverse mutation assay was used to evaluate the mutagenic potential of the test usbstance. The study was conducted in accordance with OECD Guideline 471 using the pate incorporation method. The assay was conducted using Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli tester strain WP2 uvra. The initial toxicity-mutation assay was conducted in duplicate at concentrations of 1.5, 5.0, 50, 150, 500, and 5000 µg/plate. Duplicates of water (vehicle control) and positive controls were also tested. The confirmatory mutagenicity assay was conducted 50, 150, 500 and 5000 µg/plate. A vehicle control and positive controls were also tested in triplicate. No positive mutagenic responses were observed in any strain in the presence or absence of S9 activation. Neither precipitate nor toxicity was observed during the study. Therefore, based on the results of the study, the test substance is negative for mutagenicity in bacterial cells.

Reference 6

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data taken from accepted publication with limited details on methods and results.

Justification for type of information:

Additional documentation, provided within the IUCLID Assessment Reports (Section 13), supports the read-across approach.

Qualifier:

according to guideline

Guideline:

OECD Guideline 487 (In vitro Mammalian Cell Micronucleus Test)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell micronucleus test

Species / strain / cell type:

lymphocytes: human peripheral blood

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

500, 1000, 1642 µg/mL

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

cyclophosphamide

other: Vinblastine sulfate

Details on test system and experimental conditions:

Human peripheral blood lymphocytes were obtained from a healthy non-smoking 26-year-old adult male with no recent history of radiotherapy, viral infection, or drug administration. The highest concentration analysed in each treatment condition (1642 µg/mL) is equivalent to 10 mM as recommended by the test guideline. Cells were incubated with the test substance, negative control, or positive control for 4 hours in the presence or absence of activation and for 24 continuous hours in the absence of activation. All cultures were prepared in duplicate. At the end of the short-term exposures, cells were treated with the cytokinesis inhibitor cytochalasin B and incubated for an additional 20 hours. For cell cultures under long-term exposure, cytochalasin B was added at the beginning of treatment. At the end of the 24-hour incubation period, the cells were fixed, resuspended, and applied on clean microscope slides, which were then dried and stained with acridine orange. The cytokinesis-blocked proliferation index and percentage of cytostasis were calculated from 500 cells per culture. The presence of micronuclei was scored for slides from three Neu5Ac treatment groups per exposure condition. The percent frequency of micronucleated binucleated cells in 2000 binucleated cells per concentration (minimum of 1000 binucleated cells from each culture) was calculated.

Evaluation criteria:

A response was categorized as positive in the micronucleus test if the frequency of micronucleated binucleated cells was statistically significantly increased compared to the negative control value at one or more concentrations.

Statistics:

Data on the percent frequency of micronucleated binucleated cells were subjected to Fisher’s exact test (one-sided tail) for pair-wise comparisons, and significance analyzed at the 0.05 significance level.

Species / strain:

lymphocytes: human peripheral blood

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

lymphocytes: human peripheral blood

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No significant differences were observed in the percentage of micronucleated binucleated cells between any of the test concentrations analysed and the negative control. Treatment with the positive control agents resulted in significant increases in the percentage of micronucleated binucleated cells compared to the negative control. All negative and positive control results were within the range of historical values.

Remarks on result:

other: 4-hour exposure

Conclusions:

Negative with and without activation (4-hour exposure)
Negative without activation (24-hour exposure)

Executive summary:

Human peripheral blood lymphocytes were exposed to the test substance at concentrations of 500, 1000, and 1642 µg/mL for 4-hours with activation and 4 or 24 hours without activation in accordance with OECD Guideline 487. No significant differences were observed in the percentage of micronucleated binucleated cells between any of the test concentrations analysed and the negative control. Under the conditions of this study, the test substance was considered negative for the induction of micronuclei in vitro in human peripheral blood lymphocytes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

In Vivo (Clastogenic effects - mammalian): QSAR; in vivo mouse micronucleus study; Negative. Reliability = 2.

Link to relevant study records

Reference

Endpoint:

genetic toxicity in vivo, other

Remarks:

in vivo micronucleus QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

no guideline available

Principles of method if other than guideline:

Times v.2.27.17.6 in QSAR Toolbox
Toolbox prediction report is attached in IUCLID

GLP compliance:

no

Specific details on test material used for the study:

SMILES: CC{P+}(O)C{P+}(O)C{P-}(O)C{P-}(O)C=O

Key result

Genotoxicity:

negative

Remarks:

Mammalian erythrocytes and/or peripheral blood

Remarks on result:

other: no mutagenic potential (based on QSAR/QSPR prediction)

Conclusions:

Negative

Executive summary:

The Times model for in vivo micronucleus assay was used within the QSAR Toolbox. The prediction was negative. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Qualitative structure activity relationships (QSAR), documented in QMRF/QPRF, predict no alerts to indicate likely mutagenic potential. The test substance is expected to be non-mutagenic in Ames with or without metabolic activation, negative for chromosomal aberrations with or without activation, and negative for in vivo micronuclei.  In addition, supporting data on a structurally-related chemical (L-fucose), produced negative results in in vitro assay (bacterial reverse mutation and micronucleus assay).

Justification for classification or non-classification

The test substance is not predicted to have the potential to be mutagenic or clastogenic in vitro or in vivo based on assay-specific model predictions. Additionally, data on a structurally-related chemical (L-fucose) support this conclusion. Therefore, the substance does not need to be classified for mutagenicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.