Determining a Specific Migration Limit (SML) for a data-deficient compound identified in food labels
Client
Product label and packaging manufacturer.
Background
The client was informed by a supplier that a compound with a worrying structure was present within a food label ink. As a Food-Contact Material (FCM), the client wanted the associated health risks assessed.
Project goals
Bibra was asked to review the relevant toxicological literature and, in the absence of suitable and compound-specific toxicity data, identify appropriate read-across analogues that could be evaluated to ultimately derive a Tolerable Daily Intake (TDI) and Specific Migration Limit (SML). [The SML is defined as the maximum permitted amount of a given substance released from a material or article into food or food simulants.]
Approach and outcome
Comprehensive literature searches identified only limited substance-specific toxicity data, but a range of structurally related analogues with more robust toxicological datasets came to the rescue. Quantitative Structure-Activity-Relationship (QSAR) analysis was also conducted to determine mutagenic potential, as well as to support the read-across.
A variety of potentially critical adverse effects were identified. These included carcinogenicity, reproductive toxicity, neurotoxicity and effects on the liver and kidneys.
For each of these endpoints, critical Points of Departure (PoDs) were established from the key laboratory animal studies. Suitable Uncertainty factors were then applied to the PoDs to account for interspecies and interhuman variation, the duration of the key study, extrapolation from a Lowest-Observed-Adverse-Effect Level (LOAEL) to a No-Observed-Adverse-Effect Level (NOAEL), any study limitations, and/or the use of read-across, as necessary, to generate TDI values.
The lowest and therefore most conservative TDI could then be converted to a SML (mg/kg food) by multiplying by the standard adult body weight of 60 kg and dividing by the default amount of food consumed daily, which is typically assumed to be 1 kg in the EU and UK.
The resulting SML could then be used by the client in determining whether any migration of this compound from the label to food products presents a potential health risk to consumers.
