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Toxicological information

Genetic toxicity: in vitro

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Administrative data

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:
published 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study by a reputable U.S. Government laboratory following a protocol equivalent/similar to OECD guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Principles of method if other than guideline:
Plate incorporation assays were performed as recommended by Ames et al. with the modifications of Andrews et al., published elsewhere
[Andrews, A.W., L.H. Thibault and W. Lijinsky, The relationship between carcinogenicity and mutagenicity of some polynuclear hydrocarbons,
Mutation Res., 51 (1978) 311 - 318]
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Allantoin




Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA1535, TA1538, TA98, TA 100
Details on mammalian cell type (if applicable):
Tester strains were used with and without liver microsomal fraction (S9) derived from Arocolor 1254-induced male rats or hamsters at a
concentration of 3 mg protein per plate.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
not specified
Test concentrations with justification for top dose:
1000 µg (Allantoin)
Vehicle / solvent:
Solvent used: DMSO
Controls
Untreated negative controls:
yes
Remarks:
cells only
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
Sodium nitrite control
Positive control substance:
other: Sodium nitrite
Remarks:
each with and without S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: plate incorporation
SELECTION AGENT (mutation assays): Allantoin

Evaluation criteria:
The number of revertants was considered to be significant when greater than twice the mean of the appropriate control values.
Statistics:
no data

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA1535, TA1538, TA98, TA 100
Metabolic activation:
not specified
Genotoxicity:
negative
Remarks:
for allantoin
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
Because of no qualitative differences in the results between rat and hamster S9, only the data using S9 derived from rats are reported.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No N-nitroso derivatives of allantoin were isolated, neither with nor without HONO. Therefore Allantoin is regarded as being non mutagenic.

The mean number of revertants produced by Alantoin and controls are depicted in the table below:

 Test compound  Concentration (microgram)  HONO  TA1535    TA1538    TA98    TA100  
       - S9  + S9 - S9

 + S9  - S9  + S9  - S9  + S9
 None (cells only)  -  -  12  15  11  21  17  37  103  113
 DMSO  -  -  12  13  7  21  17  29  92  109
 Sodium nitrite control  -  +  7  12  6  21  16  32  87  104
 Allantoin  1000  -  6  29  10  16  12  

39

 
 101  162
 Allantoin  1000  +  12  18  10  20  16  36 133   118

Applicant's summary and conclusion

Conclusions:
Allantoin was not mutagenic alone or after nitrosation in the test methods described here.