di-, tri- and tetrachlorotetradecane

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Adequate read-across data are available on alkanes, C14 -17, chloro to predict the properties of  di-, tri-, tetrachlorodecane. OECD 471 guideline study carried out with test item (C14-17 chlorinated paraffin; 42% chlorination). The results show the test item was not mutagenic in the Ames assay with five Salmonella typhimurium strains,  with or without the addition of a rat liver metabolic activation system.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

End points of target substance di-, tri-, tetra- chlorotetradecane can be read across from source substance Alkanes, C14-17, chloro EC number: 287-477-0 | CAS number: 85535-85-9. This due to the following comparison:
1) di-, tri-, tetra- chlorotetradecane components make up the C14 content found in Alkanes, C14-17, chloro. It is therefore logical that di-, tri-, tetra- chlorotetradecane has been tested as a component of the larger group Alkanes, C14-17, chloro EC number: 287-477-0
2 )The target and read-across molecules are both straight chain and therefore it is considered there are no major difference in steric hindrance between the substances (due to branched chain structures)
3) The functional groups are consistent between the target and read across substances, both are predominantly chlorinated alkanes

To increase the accuracy of the read across, studies used from the Alkanes, C14-17, chloro REACH dossier will only include studies that used C14 components and similar levels of chlorination to di-, tri-, tetra- chlorotetradecane – 35 to 52 % chlorination.

For the above reasons the required endpoint is sufficiently covered by the testing on the read across substance Alkanes, C14-17, chloro EC number: 287-477-0 and the hazard adequately assessed. It is therefore considered that further testing on vertebrates is not required.

Reason / purpose for cross-reference:

read-across source

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

no data

Data erroneously reported for Salmonella typhimurium strain TA199 in IPCS EHC 181 (1996), should read strain TA100

Conclusions:

Interpretation of results from OECD 471 guideline study - negative. The test item (C14-17 chlorinated paraffin; 42% chlorination) was not mutagenic in the Ames assay with five Salmonella typhimurium strains, with or without the addition of a rat liver metabolic activation system.

Executive summary:

No study has been reported for di-, tri-, tetra- chlorotetradecane, but data have been reported for the principal constituents of di-, tri-, tetra- chlorotetradecane that are found in the similar substance Alkanes, C14-17, chloro. However, as Alkanes, C14-17, chloro contains a broad range of chloro-alkanes, only reports using test material containing C14 chloro-alkanes and similar levels of chlorination (35 to 52 % chlorination) have been used for the purposes of read across.

Interpretation of results from OECD 471 guideline study - negative. The test item (C14-17 chlorinated paraffin; 42% chlorination) was not mutagenic in the Ames assay with five Salmonella typhimurium strains,  with or without the addition of a rat liver metabolic activation system..

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

End points of target substance di-, tri-, tetra- chlorotetradecane can be read across from source substance Alkanes, C14-17, chloro EC number: 287-477-0 | CAS number: 85535-85-9. This due to the following comparison:
1) di-, tri-, tetra- chlorotetradecane components make up the C14 content found in Alkanes, C14-17, chloro. It is therefore logical that di-, tri-, tetra- chlorotetradecane has been tested as a component of the larger group Alkanes, C14-17, chloro EC number: 287-477-0
2 )The target and read-across molecules are both straight chain and therefore it is considered there are no major difference in steric hindrance between the substances (due to branched chain structures)
3) The functional groups are consistent between the target and read across substances, both are predominantly chlorinated alkanes

To increase the accuracy of the read across, studies used from the Alkanes, C14-17, chloro REACH dossier will only include studies that used C14 components and similar levels of chlorination to di-, tri-, tetra- chlorotetradecane – 35 to 52 % chlorination.

For the above reasons the required endpoint is sufficiently covered by the testing on the read across substance Alkanes, C14-17, chloro EC number: 287-477-0 and the hazard adequately assessed. It is therefore considered that further testing on vertebrates is not required.

Reason / purpose for cross-reference:

read-across source

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

True negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

Interpretation of results: negative C14-17 chlorinated paraffin; 45% chlorination at up to of 5000 µg/plate was not mutagenic in an Ames test with five Salmonella typhimurium strains in the presence or absence of a mammalian metabolic activation system (S9). No data was reported relating to positive or negative controls or cytotoxicity.

Executive summary:

No study has been reported for di-, tri-, tetra- chlorotetradecane, but data have been reported for the principal constituents of di-, tri-, tetra- chlorotetradecane that are found in the similar substance Alkanes, C14-17, chloro. However, as Alkanes, C14-17, chloro contains a broad range of chloro-alkanes, only reports using test material containing C14 chloro-alkanes and similar levels of chlorination (35 to 52 % chlorination) have been used for the purposes of read across.

Interpretation of results: negative C14-17 chlorinated paraffin; 45% chlorination at up to of 5000 µg/plate was not mutagenic in an Ames test with five Salmonella typhimurium strains in the presence or absence of a mammalian metabolic activation system (S9). No data was reported relating to positive or negative controls or cytotoxicity.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

End points of target substance di-, tri-, tetra- chlorotetradecane can be read across from source substance Alkanes, C14-17, chloro EC number: 287-477-0 | CAS number: 85535-85-9. This due to the following comparison:
1) di-, tri-, tetra- chlorotetradecane components make up the C14 content found in Alkanes, C14-17, chloro. It is therefore logical that di-, tri-, tetra- chlorotetradecane has been tested as a component of the larger group Alkanes, C14-17, chloro EC number: 287-477-0
2 )The target and read-across molecules are both straight chain and therefore it is considered there are no major difference in steric hindrance between the substances (due to branched chain structures)
3) The functional groups are consistent between the target and read across substances, both are predominantly chlorinated alkanes

To increase the accuracy of the read across, studies used from the Alkanes, C14-17, chloro REACH dossier will only include studies that used C14 components and similar levels of chlorination to di-, tri-, tetra- chlorotetradecane – 35 to 52 % chlorination.

For the above reasons the required endpoint is sufficiently covered by the testing on the read across substance Alkanes, C14-17, chloro EC number: 287-477-0 and the hazard adequately assessed. It is therefore considered that further testing on vertebrates is not required.

Reason / purpose for cross-reference:

read-across source

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

Interpretation of results: negative C14-17 chlorinated paraffin; 40% chlorination was not mutagenic in a bacterial mutation assay using the plate incorporation and pre-incubation methods when incubated at up to 5000 ug/plate with five strains of Salmonella typhimurium, in the presence or absence of a rat liver metabolic activation system.

Executive summary:

No study has been reported for di-, tri-, tetra- chlorotetradecane, but data have been reported for the principal constituents of di-, tri-, tetra- chlorotetradecane that are found in the similar substance Alkanes, C14-17, chloro. However, as Alkanes, C14-17, chloro contains a broad range of chloro-alkanes, only reports using test material containing C14 chloro-alkanes and similar levels of chlorination (35 to 52 % chlorination) have been used for the purposes of read across.

Interpretation of results: negative C14-17 chlorinated paraffin; 40% chlorination was not mutagenic in a bacterial mutation assay using the plate incorporation and pre-incubation methods when incubated at up to 5000 ug/plate with five strains of Salmonella typhimurium, in the presence or absence of a rat liver metabolic activation system.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Two other in vitro gene mutation studies were carried out on C14 -17 45% chloriantion and C14 -17 40% chloriantion. The results were all negative for five Salmonella typhimurium strains,  with or without the addition of a rat liver metabolic activation system.

Justification for classification or non-classification

Using read across from negative results of three Ames tests carried out on C14 -17 42% chloriantion, C14 -17 45% chloriantion and C14 -17 40% chloriantion we can expect di-, tri- and tetrachlorotetradecane not to be mutagenic in vitro and therefore does not meet the EU classification criteria.