Table 2.

Knowledge gaps and problems in the RA of FCMs, description of the shortcoming in risk assessment, and recommendation for overcoming the gap.

No.	Knowledge gap or problem	Description	Recommendation
I	Risk assessments (RAs) focus on starting substances, not on the finished article	Focus is placed on chemicals at the start of the manufacturing process instead of those present in the finished food contact article and migrating into food, i.e., the chemicals people are exposed to.	Ensure adequate toxicological assessment of food contact articles: Assess all food contact chemicals (FCCs) with the potential to migrate from the finished food contact article (including printing inks, labels, closures, etc.).
II	Unknown substances migrate from food contact articles (FCAs) into food	The chemical identity of some/many substances in food contact articles is unknown; therefore, no RA using the current approach is possible: neither exposure nor hazard can be assessed.	Ensure adequate toxicological assessment of FCCs, and avoid intentional use of chemicals with unknown toxicity: Assess overall migrate or extract from the finished FCA, e.g., by using in vitro bioassays and subsequent chemical analysis.
III	Authorized chemicals are not available as pure analytical standards: exposure cannot be assessed and legal limits cannot be enforced	Legally binding migration limits cannot be controlled and enforced because analytical and calibration methods for many authorized FCCs are unavailable and postmarket exposure assessments are not possible.	Limit intentionally used FCCs to chemicals with analytical standards: Reevaluate authorization status for chemicals based on the availability of chemical standards. Introduce mandatory requirement for users of an intentionally added substance to have a pure analytical standard available for authorities to enforce legal limits.
IV	Human exposure estimates are outdated and not publicly accessible	Human exposure estimates are based on premarket data, which is not transparent, and there is no systematic postmarket assessment of authorized substances.	Make all data used for human exposure assessment available to public review. Require mandatory data notification on chemical use to authorities. Perform periodic reviews of human exposure for all authorized FCMs.
V	Cumulative exposures are not taken into consideration when exposures are estimated	Exposures from sources other than food contact articles are not generally considered for exposure assessments, because information is often unavailable.	Share chemical use information between authorities to assess actual human exposures. Expand biomonitoring efforts.
VI	Generic toxicological thresholds are used in the absence of actual data, and available toxicological data are insufficient for RAs	For many nonintentionally added substances (NIAS), RAs rely on generic toxicological thresholds (TTCs), which may not be sufficiently protective. Endocrine disruptors are not routinely assessed, developmental toxicity data are generated for highest exposure estimates only (based on premarket exposure assumptions).	Avoid chemicals with unknown toxicity. Ensure adequate toxicological assessment of FCCs. Assess validity of TTCs by using recent data from chronic toxicity studies. Use TTCs and in silico data (e.g., from quantitative structure-activity relationship (QSAR) computational models) only intermediately for filling data gaps and prioritization for toxicity testing, and require toxicity data for any food contact chemical migrating into food.
VII	Mixture toxicity of the overall migrate is not assessed	Overall migrate into food is not assessed for its mixture effect even though humans are generally exposed to mixtures of chemicals from food packaging.	Ensure adequate toxicological assessment of FCCs. Assess overall migrate from the finished food contact article (including printing inks, labels, closures, etc.) using bioassays.
VIII	Hazard characterization does not consider some of the most relevant diseases in the human population	Hazards associated with non-communicable diseases like cardiovascular disease or metabolic syndrome are not routinely assessed, even though these are of very high relevance to public health.	Ensure adequate toxicological assessment of FCCs. In addition to genotoxicity testing, require toxicity data on cardiovascular, metabolic, and endocrine endpoints for any food contact chemical migrating into food at any level.
IX	Conflicts of interest are systemic to the current risk assessment approach	Risk assessment may be performed by industry, without public oversight, and data provided to authorities for risk assessment may be from studies commissioned by the applicant that are not publicly available.	FCC risk assessment should be performed by independent third parties. Data should be public. Notification of a safety decision by industry should be mandatory (i.e., authorities are informed about the use/presence of an FCC).