Health risk assessment of extractables – a rubber stopper

Client

A pharmaceutical company.

Background

The company had commissioned extractables and headspace analyses on a rubber stopper, part of a container‑closure system for storing a product intended for occasional, repeated injection into the eyes to treat macular degeneration.

Project Goals

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

Approach

Bibra assessed whether the estimated exposures to the extractables might pose any significant health risk to patients.

The estimated, occasional doses of inorganics were considered toxicologically negligible. The organic extractables were assessed briefly for both thresholded toxicity risk and non-thresholded toxicity (mutagenicity/genotoxic carcinogenicity) risk. At the estimated concentrations, none were anticipated to cause eye irritation, so the focus was on systemic effects.

In regard to non-threshold toxicity, experimental data, supported by the Toxtree structure-activity relationship (SAR) modules, were adequate to conclude that the chemically-identified extractables lack mutagenic character. One carcinogen was identified and the highly-precautionary cancer unit risk figure derived by the US EPA was used to confidently demonstrate that the estimated exposure would not pose any significant cancer risks to patients.

Experimental toxicity data and tolerable exposure values established by Expert Groups or proposed in REACH dossiers, together with support from TTC, concepts were sufficient for a confident conclusion that none of the extractables would pose any significant risk of systemic, thresholded toxicity.

Project Outcome

The client was provided with a health risk assessment report concluding that the analytical extractables and headspace studies had not detected any extractables (potential leachables) that would pose any significant health risks to patients exposed by occasional, repeated, intravitreal injection, for many years. Thus, the studies provided reassurance over use of the rubber stopper.

Project Leader

Pete Watts

 

(Q)SAR

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