N,N'-diisopropylethane-1,2-diaminium (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: (Q)SAR in silico prediction tool

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Materials and methods

Type of study / information:

(Q)SAR method report

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Type:

Constituent

Results and discussion

Any other information on results incl. tables

In toxicologicalin silicoprofile DIPEDA Clavulanate was tested against carcinogenicity, chromosome damage, genotoxicity, hepatotoxicity, hERG channel inhibition, irritation, miscellaneous endpoints, mutagenicity, ocular toxicity, reproductive toxicity, respiratory sensitization, skin sensitization and thyroid toxicity endpoints.

In silicostructural alerts concerning respiratory and skin sensitisation were identified by DEREK toxicity software. Both alerts were classified as plausible (Table 1).

DIPEDA component

A recent review of the respiratory toxicology of ethylenediamine and piperazine byHSEconsidered that these chemicals meet the revised EU criteria for classification as a respiratory sensitiser and labelling with the risk phrase R42[1].

There are fewer reports of asthma due to diethylenetriamine and triethylenetetramine than on ethylenediamine and piperazine[3, 4, 5, 6]. Alkyl ethylenediamines of simple structure such as the above or their salts with simple acids such as hydrochloric acid, may produce, when inhaled over a period of months or years, asthma, usually in a minority of exposed workers. At least for relatively low exposure concentrations a latent period of exposure is required for the development of asthmatic symptoms[4, 5, 6].

Clavulanate component

The presence of a skin sensitisation structural alert within a molecule indicates the molecule has the potential to cause skin sensitisation. Whether or not the molecule will be a skin sensitiser will also depend upon its percutaneous absorption. Generally, small lipophilic molecules are more readily absorbed into the skin and are therefore more likely to cause sensitisation[7, 8].

Thus, DIPEDA Clavulanate is expected to show a considerable likelihood to be active as respiratory and skin sensitiser.

Applicant's summary and conclusion

Conclusions:

According to DEREK (Q)SAR prediction tool, DIPEDA Clavulanate is expected to show a considereable likelyhood to be active as a respiratory and skin sensitizer.