1,3,5-Triazine-2,4,6-triamine, deammoniated

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames-Test:

The test item didn't show mutagenic effects in both experiments. The number of revertant colonies was not increased in comparison with the spontaneous revertants (solvent only). Cytotoxicity of the test item was not detected. The background lawn was visible and the number of revertants was not significantly decreased. Therefore it can be stated, that under the test conditions, the test item MELON 1,3,5-Triazine-2,4,6-triamine, deammonated is not mutagenic in the Bacterial Reverse Mutation Test using Salmonella typhimurium, strains TA 97a, TA 98, TA 100, TA 102 and TA 1535.

In vitro micronucleus test/mouse lymphoma assay:

According to section 1 of REACH Regulation (EC) Annex XI, testing for genetic toxicity does not need to be conducted if testing does not appear scientifically necessary. For genetic toxicity 1,3,5-Triazine-2,4,6-triamine, deammoniated will have to be made bioavailable to the target gene in sufficient concentration to cause the mutagenic effect. This requires that the polymer molecules will have to be bioavailable by absorption via relevant routes of exposure. It is therefore unlikely to occur with this insoluble substance .  Since the gut wall presents a substantial barrier to prevent uptake of high molecular weight substances, 1,3,5-Triazine-2,4,6-triamine, deammoniated is unlikly to cross the gastro-intestinal epithelium and to become systemically available for distribution to internal target tissues and organs.  Considering the above mentioned factors,  1,3,5-Triazine-2,4,6-triamine, deammoniated is obviously devoid of toxicity via the oral route, i.e. (in vivo) genetic toxicity is no relevant toxicological endpoint.  This applies also for any dermal exposure because permeation of a chemical through the Stratum corneum is basically a diffusion process in which active transport plays no role. The layer with the highest resistance to diffusion is the rate-limiting membrane. For many compounds,the lipophilic Stratum corneum is the primary or rate-limiting barrier.  According to the so-called “Dalton rule” the molecular weight of a molecule may not exceed 500 Dalton (500 g/Mol) for a quantitative relevant skin penetration. The molecular weight of 1,3,5-Triazine-2,4,6-triamine, deammoniated is expected to be higher than 500 g/Mol (see mass spectrum and HPLC-analysis). In addition 1,3,5-Triazine-2,4,6-triamine, deammoniated is insoluble in water and not fat soluble, consequently it is not expected to be absorbed through the skin. Taking this into account, dermal absorption of 1,3,5-Triazine-2,4,6-triamine, deammoniated is not expected.  The other appropriate route of exposure to 1,3,5-Triazine-2,4,6-triamine, deammoniated is the inhalative one which is also of no relevance due to the bio-inertness of the substance.    The executed bacterial reverse mutation assay in bacteria with 1,3,5-Triazine-2,4,6-triamine, deammoniated supports the above outlined rationale that this insoluble and bio-inert substance is devoid of any mutagenic properties.  

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The GLP study was conducted according to an internationally accepted guideline (OECD 471). All study parameters are based on the specific guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

other: TA97a, TA98, TA100, TA102, TA1535

Details on mammalian cell type (if applicable):

Mutations:
TA97a: hisD6610, uvrB, pKM 101, rfa
TA 98: hisD3052, uvrB, pKM 101, rfa
TA 100 : hisG46, uvrB, pKM 101, rfa
TA102: hisG428, pKM 101, rfa
TA1535: hisG46, uvrB, rfa.

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

Plate incorporation method: 5005 / 1502 / 515 /148 / 54 µg/plate

Vehicle / solvent:

The test item was suspended in sterile H2O demin.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 4-Nitro-1,2-phenylene diamine

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-Amino-anthracene

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Evaluation criteria:

A test item is considered to have mutagenic potential, if a significant, reproducible increase of revertant colonies per plate (increase factor > 2) in at least one strain can be observed. A concentration-related increase over the range tested can also be taken as a sign of mutagenic activity.

Species / strain:

other: TA97a, TA98, TA100, TA102, TA1535

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

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative

The test item MELON 1,3,5- Triazine-2,4,6-triamine, deammonated is not mutagenic under the conditions of the test.

Executive summary:

The test item didn't show mutagenic effects in both experiments. The number of revertant colonies was not increased in comparison with the spontaneous revertants (solvent only). Cytotoxicity of the test item was not detected. The background lawn was visible and the number of revertants was not significantly decreased. Therefore it can be stated, that under the test conditions, the test item MELON 1,3,5-Triazine-2,4,6-triamine, deammonated is not mutagenic in the Bacterial Reverse Mutation Test using Salmonella typhimurium, strains TA 97a, TA 98, TA 100, TA 102 and TA 1535.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint

Only one in vitro study available, further testing waived, see respective endpoint study records

Justification for classification or non-classification

The bioavailability of the registered substance is -based on scientific reasoning- negligible. From this follows, that a relevant genetic toxicity is not likely and not expected.  

Therefore the substance has not to be classified for germ cell mutagenicity.