CHemical RISk calculators (CHRIS) - Color additives RST

Identity - Select the color additive in the component being evaluated via the pull down list. If the color additive is not explicitly listed, please choose either "Other metal oxide color additive" or "Other non-metal oxide color additive" and enter the chemical name, including CAS # if known. If "Other non-metal oxide color additive" is selected, please enter the molecular weight of the color additive in grams per mole. If you are evaluating an additive associated with a color additive please select "Other color additive associated compound" and enter the chemical name and molecular weight. Note that CHRIS is limited to color additive associated substances with molecular weight between 100 and 1100 g/mol. For compounds with molecular weight > 1100 g/mol, this value can be used for a conservative exposure estimate.

Molecular weight - Enter the molecular weight of the substance in grams per mole.

Amount - Enter the total mass of the substance in the component being evaluated expressed in milligrams.

Total impurity concentration - If you have selected a color additive, please enter the combined concentration of all impurities associated with the color additive as a percentage (% mass/mass).

Matrix - Please select your polymer matrix from the list. If your polymer is not listed below, please select "Other polymer". For polymer mixtures/blends, co-polymers, or composites (e.g. glass fiber reinforced matrices), the component or phase that is worst-case for exposure, i.e. the softest or least glassy (lowest Tg) component can be selected if listed (which, in turn, assumes the entire system is composed of the worst-case component or phase). In these scenarios, a justification should be provided for the choice of worst-case component of the polymer system.

Mass - Enter the mass of the polymer matrix in grams.

Density - Enter the estimated density of the polymer matrix in grams per cubic centimeter. Note that a rough estimate (e.g. +/- 10%) is acceptable.

Exposed surface area - Enter the patient contacting surface area of the color additive containing component being evaluated in square centimeters. This includes both direct and indirect patient contact.

Exposure type - Select the appropriate exposure category: > 30 days = long-term, > 24 hours - 30 days = prolonged, ≤ 24 hours = limited. For limited exposures (≤ 24 hours), please enter the maximum exposure time in hours.

The exposure model relies on assumptions that are typically valid for bulk solutes in polymeric device components. However, if any of the assumptions are violated the exposure calculation may not remain protective. Therefore, if the output of CHRIS is used to support a submission to CDRH, users must confirm conformance to the underlying assumptions or provide supporting justification. Examples of considerations when confirming conformance are provided below:

Biostability of the matrix - While many of the matrices listed within CHRIS will not appreciably swell or degrade in any physiological environment, this can not be generalized. For example, silicones may swell in lipid-rich environments. Chemical compatibility of the polymer matrix with the use environment can be assessed based on historical use and/or evaluation of swelling and/or degradation propensity in physiologically relevant media.

Particle/aggregate size and distribution - CHRIS relies on the color additive having a distribution that is macroscopically homogeneous within the matrix (e.g. CAs used for surface marking would be excluded); thus, any particles or aggregates must be small relative to the component and homogeneously distributed. This can be confirmed/justified through the use of particle coatings and/or dispersants in the concentrate to prevent aggregation and promote homogeneity, macroscopic observations of color uniformity, and/or microscopic observations to evaluate the potential for surface segregation phenomena, such as blooming.

Dilute concentration - The model relies on a concentration independent diffusion coefficient, which assumes any color additives are present only in dilute quantities. Confirming that the total amount of color additives present is ≤ 2 m/v % is sufficient to conform with this assumption. It may be possible to justify that the CHRIS calculation for a dilute compound will remain protective if the total concentration is in excess of 2 m/v %, if the presence of additional compound could reasonably be expected to inhibit rather than promote diffusion, e.g. second phase particulates.

Matrix stability - The model parameters/transport properties are established using worst-case values reported in the literature. However, it is unclear if the reported values account for potential degradation (e.g. during sterilization) or other physicochemical changes (e.g. excessive plasticization) that may occur during manufacturing and negatively impact these values. Polymer stability can be confirmed/justified by evidence supporting that manufacturing (including sterilization) does not alter the matrix material of the final device.