In an article published on July 21, 2017 in the peer-reviewed journal Food Additives & Contaminants: Part A, Julien Veyrand and colleagues from Nestlé Research Center, Lausanne, Switzerland, presented an empirical study evaluating the suitability of in vitro bioassays for use in safety assessments of food contact materials (FCMs).
Especially in risk assessments of non-intentionally added substances (NIAS), “the combination of bioassays, analytical chemistry and risk assessment has been promoted as a new paradigm to identify toxicologically relevant molecules and address safety issues” (FPF reported). Multiple studies have already demonstrated the activity of extracts or migrates from FCMs in a variety of bioassays (see FPF review article). However, “the actual value of in vitro bioassay data is still highly debated,” because still relatively little is known regarding such issues as “safety significance of in vitro biological activities” or “adequacy of the limits of detection of bioassays,” the authors noted.
In order to “determine and illustrate the potential merits” of a bioassay-based approach, the authors worked with a polystyrene (PS)-based FCM containing tris(nonylphenyl)phosphite (TNPP, CAS 26523-78-4), an antioxidant known to degrade into 4-nonylphenol (NP, CAS 104-40-5). This degradation product is known to have estrogenic and anti-androgenic activities, and both of these could indeed be observed by the authors in the performed bioassays.
However, compared to the activity calculated on the basis of NP levels measured in the FCM migrates using chemical analytics, estrogenic and anti-androgenic activities observed in the bioassays were 24% lower and 74% higher, respectively. This discrepancy may be explained either by a difference in the composition of NP isomers present in the reference substance and in actual FCM extracts, or by the additional effects exerted by other simultaneously migrating substances present in the mixture.
Importantly, the levels of NP which were measured by chemical analytics and bioassays were (i) comparable and (ii) relevant for risk assessment. The latter conclusion was reached by considering several exposure scenarios driven by either infants and toddlers, or adults. Depending on the exposure scenario, NP exposure was found to be “lower, close or slightly higher” than the respective Acceptable Daily Intake (ADI) values. These findings showed that NP levels measurable with bioassays “are well within those [levels] required to adequately assess safety,” thus confirming that the applied bioassays are sufficiently sensitive to detect the presence of substances of concern at ADI-relevant levels.
Furthermore, this study also demonstrated that “a bioactivity in a [FCM] migrate does not necessarily constitute a safety issue,” since addressing the concern “requires the application of risk assessment,” the authors emphasized. In this approach, risk assessment performed subsequently to a bioassay-based measurement is expected to show whether the detected bioactivity represents a safety concern or not, assuming there are safe exposure levels as is common in chemical risk assessment. However, others have pointed out that it is uncertain whether safe exposure levels exist for endocrine disrupting chemicals (FPF reported), and further questioned the public health effectiveness of the ‘safe levels’ assigned by current risk assessment procedures (FPF reported).
Veyrand, J., et al. (2017). “Integrating bioassays and analytical chemistry as an improved approach to support safety assessment of food contact materials.” Food Additives & Contaminants: Part A (published July 21, 2017).