Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Evidence was provided to suggest that TDCP is a bacterial cell mutagen in vitro. Positive responses were seen in the mutation assay, following metabolic activation only. Some papers reviewed included positive data for possible metabolites of TDCP. In mammalian cell studies, TDCP caused mutations in mouse lymphoma L5178Y cells in the presence of metabolic activation.  TDCP also caused an increase in the occurrence of chromosomal aberrations in mouse lymphoma cells, again in the presence of metabolic activation. However, in a chromosomal aberration study in CHO cells, no increase in cells with chromosome aberrations or polyploidy were recorded.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

In vivo, TDCP was not clastogenic in a mouse micronucleus assay and was found not to induce unscheduled DNA synthesis in studies conducted to OECD guidelines. Negative results were also obtained in a second in vivo micronucleus assay and in an in vivo/in vitrourine mutagenicity assay.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Short description of key information:
Evidence was provided to suggest that TDCP is a bacterial cell mutagen in vitro. Positive responses were seen in the mutation assay, following metabolic activation only. Some papers reviewed included positive data for possible metabolites of TDCP. In mammalian cell studies, TDCP caused mutations in mouse lymphoma L5178Y cells in the presence of metabolic activation.  TDCP also caused an increase in the occurrence of chromosomal aberrations in mouse lymphoma cells, again in the presence of metabolic activation. However, in a chromosomal aberration study in CHO cells, no increase in cells with chromosome aberrations or polyploidy were recorded. In vivo, TDCP was not clastogenic in a mouse micronucleus assay and was found not to induce unscheduled DNA synthesis in studies conducted to OECD guidelines. Negative results were also obtained in a second in vivo micronucleus assay and in an in vivo/in vitrourine mutagenicity assay.
In summary, there is some evidence to suggest that TDCP is mutagenic in vitro. However, in vivo, the mouse micronucleus assays were negative, results which were further supported by a negative result in an in vivo/in vitro unscheduled DNA synthesis assay.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is some evidence to suggest that TDCP is mutagenic in vitro. However, in vivo, the mouse micronucleus assays were negative, results which were further supported by a negative result in an in vivo/in vitro unscheduled DNA synthesis assay.