D-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: OCC{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 with the QSAR Toolbox. The prediction was negative with activiation. 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: OCC{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 with the QSAR Toolbox. The prediction was negative without activiation. 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: OCC{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 with the QSAR Toolbox. The prediction was negative with activiation. 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: OCC{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 with the QSAR Toolbox. The prediction was negative without activiation. Additional supporting documentation is provided in the prediction report attached in IUCLID.

Reference 5

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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:

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 report section supports the read across approach.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

histidine

Species / strain / cell type:

S. typhimurium TA 98

Metabolic activation:

with

Metabolic activation system:

S9 mix containing 5% chlorophene-induced rat liver

Test concentrations with justification for top dose:

not reported

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Conclusions:

Interpretation of results (migrated information):
negative

Test item was negative in this experiment

Executive summary:

The result of a bacteria mutation assay with Salmonella typhimurium strain TA 98 with S9 showed that the test item produced no mutagenic activity.

Reference 6

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

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:

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 report section supports the read across approach.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Target gene:

histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 microsomal activation mixture

Test concentrations with justification for top dose:

0.05, 0.5, 5, 50 and 500 µg/plate

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

4-nitroquinoline-N-oxide

N-ethyl-N-nitro-N-nitrosoguanidine

cyclophosphamide

mitomycin C

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Conclusions:

Interpretation of results (migrated information):
negative

The test item was negative in this experiment.

Executive summary:

The result of a bacteria mutation assay with Salmonella typhimurium strains TA1535, TA1537, TA98, and TA100 with and without S9 activation showed that the test item produced no mutagenic activity.

Reference 7

Endpoint:

in vitro cytogenicity / micronucleus study

Remarks:

Type of genotoxicity: chromosome aberration

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:

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 report section supports the read across approach.

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

in vitro micronucleus test with hamster embryo cells

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell micronucleus test

Target gene:

differentiating erythrocytes

Species / strain / cell type:

mammalian cell line, other: Syrian hamster embryo

Metabolic activation:

without

Test concentrations with justification for top dose:

The concentration range finding and the assessment of dose dependence were performed as described in Schmuck, G. et al. (1988) Mutation Res., 203, 397-404

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

benzo(a)pyrene

methylmethanesulfonate

other: Aflatoxin B1; Benzylchloride; Diethylstilbestrol; N-Methyl-N-nitrosourea

Species / strain:

mammalian cell line, other: Syrian hamster embryo

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Conclusions:

Interpretation of results (migrated information):
negative without metabolic activation

Negative without metabolic activation when tested with Syrian Hamster Embryo cells

Executive summary:

The test item was tested without metabolic activation in the SHE (Syrian hamster embryo) micronucleus test in vitro. The test item was negative in the SHE micronucleus assay.

Reference 8

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

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:

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 report section supports the read across approach.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

GLP compliance:

not specified

Type of assay:

mammalian cell gene mutation assay

Target gene:

thymidine kinase locus

Species / strain / cell type:

mouse lymphoma L5178Y cells

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 liver homogenate (S9)

Test concentrations with justification for top dose:

0, 0.179, 0.204, 0.215, 0.225, 0.235 mol/L

Untreated negative controls:

yes

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

The test substance was positive at concentrations >20 mmol/L. In the present study, the osmotic pressure was measured by the freezing point depression method, but a simple relationship between osmotic pressure and mutagenic activity was not observed for the test substance.

Conclusions:

The test substance was positive at concentrations >20 mmol/L.

Executive summary:

Mutagenicity of the test substance was examined in the mouse lymphoma assay. The test substance was positive at concentrations >20 mmol/L. In the present study, the osmotic pressure was measured by the freezing point depression method, but a simple relationship between osmotic pressure and mutagenic activity was not observed for the test substance.

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

Reference 1

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: OCC{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.

Reference 2

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

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:

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 report section supports the read across approach.

Principles of method if other than guideline:

The ability of the test substance to induce dominant lethal mutations in mice fed gamma-irradiated glucose was studied.

GLP compliance:

not specified

Type of assay:

rodent dominant lethal assay

Species:

mouse

Strain:

Swiss

Sex:

male

Route of administration:

oral: feed

Duration of treatment / exposure:

Short-term study: 7 days
Long-term study: 8 weeks

Frequency of treatment:

Continuous in feed

Post exposure period:

None

Remarks:

Doses / Concentrations:
10%
Basis:

Remarks:

Doses / Concentrations:
Short-term study: 200, 50000 Gy
Basis:
nominal in diet

No. of animals per sex per dose:

Not reported

Control animals:

other: There was a negative control group that was fed stock laboratory ration and a control group fed unirradiated glucose in addition to stock ration

Tissues and cell types examined:

Live and dead implanations. The dominant lethality was assessed in terms of pre-and post-implantation lethality.

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

not specified

Conclusions:

Interpretation of results (migrated information): negative
The test substance did not induce dominant lethal mutations in mice.

Executive summary:

The ability of the test substance to induce dominant lethal mutations in mice fed gamma-irradiated glucose was studied. The test substance did not induce dominant lethal mutations in mice.

Reference 3

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:

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 report section supports the read across approach.

Principles of method if other than guideline:

The test substance was examined for its ability to produce micronuclei in bone marrow of female mice.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

other: C57BL/6 x C3H/He

Sex:

female

Route of administration:

intraperitoneal

Duration of treatment / exposure:

Five consecutive days

Frequency of treatment:

Once daily

Post exposure period:

None

Remarks:

Doses / Concentrations:
10000 mg/kg
Basis:
other: maximum dose used

No. of animals per sex per dose:

8 females/group

Control animals:

not specified

Tissues and cell types examined:

333 reticulocytes were scored from each of 3 bone marrow preparations for a total of ~1000 per treated group.

Sex:

female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

Interpretation of results (migrated information): negative
The test substance was negative for the induction of micronuclei in bone marrow of female mice.

Executive summary:

The test substance was examined for its ability to produce micronuclei in bone marrow of mice. Female mice were given intraperitoneal injection of the test substance on five consecutive days. Reticulocytes (~1000 per treated group) were scored. The test substance was negative for the induction of micronuclei in bone marrow of female mice.

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 structurally similar chemicals (glucose and α-D-glucopyranose), produced negative results in 3 in vitro assays (bacterial reverse mutation and micronucleus assays), a positive result in 1 in vitro assay (mouse lymphoma assay), and negative in two in vivo studies (mouse micronucleus and dominant lethal 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.  Additional data on the read-across chemical 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.