Health risk assessment of extractables – a CCS consisting of a bottle, dropper, cap and label, used to store an ear drop solution

Client

A pharmaceutical company.

Background

The company had commissioned extractables and headspace analyses on a container-closure system (CCS) consisting of a bottle, cap, dropper and label.

Project Goals

Bibra toxicologists were asked to assess whether the extractables (including headspace volatiles) might pose any significant health risks to consumers.

Approach

Bibra estimated exposures that might result from use of the product and assessed whether these exposures, over many years of treatment, might pose any significant health risk to consumers.

In regard to non-threshold toxicity (mutagenicity/genotoxic carcinogenicity), experimental data, supported by structural considerations, were adequate to conclude that all but two of the chemically-identified extractables lacked genotoxic character. The two exceptions were untested but contained a structural alert for mutagenicity and these, along with three “unknowns” were assessed as potential mutagens. Application of the TTC, together with ICH M7 and PQRI guidance, showed that the estimated exposures would be associated with only negligible cancer risks, even if the compounds were later shown to be both genuine leachables and potent mutagens.

Based on experimental toxicity data and/or tolerable exposure values established by Expert Groups or proposed in REACH dossiers, supported by application of the TTC concept for untested/unidentified compounds, it was confidently concluded that the extractables would not pose any significant thresholded toxicity risks.

Project Outcome

The client was provided with a health risk assessment report that concluded that the extractables would not pose any significant health risks to the consumers, providing reassurance over the toxicological acceptability of using the CCS for the intended purpose.

Project Leader

Pete Watts

 

Extractables and Leachables

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