Allantoin

Genetic toxicity: in vitro

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

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

Test material information

Constituent 1

Reference substance name:

Allantoin

EC Number:

202-592-8

EC Name:

Allantoin

Cas Number:

97-59-6

Molecular formula:

C4H6N4O3

IUPAC Name:

1-(2,5-dioxoimidazolidin-4-yl)urea

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.