This article describes results obtained by testing the European Food Safety Authority-tiered guidance approach for safety assessment of botanicals and botanical preparations intended for use in food supplements. Main conclusions emerging are as follows. (i) Botanical ingredients must be identified by their scientific (binomial) name, in most cases down to the subspecies level or lower. (ii) Adequate characterization and description of the botanical parts and preparation methodology used is needed. Safety of a botanical ingredient cannot be assumed only relying on the long-term safe use of other preparations of the same botanical. (iii) Because of possible adulterations, misclassifications, replacements or falsifications, and restorations, establishment of adequate quality control is necessary. (iv) The strength of the evidence underlying concerns over a botanical ingredient should be included in the safety assessment. (v) The matrix effect should be taken into account in the safety assessment on a case-by-case basis. (vi) Adequate data and methods for appropriate exposure assessment are often missing. (vii) Safety regulations concerning toxic contaminants have to be complied with. The application of the guidance approach can result in the conclusion that safety can be presumed, that the botanical ingredient is of safety concern, or that further data are needed to assess safety.

Locust bean gum (LBG) is a galactomannan polysaccharide used as thickener in infant formulas with the therapeutic aim to treat uncomplicated gastroesophageal reflux (GER). Since its use in young infants below 12weeks of age is not explicitly covered by the current scientific concept of the derivation of health based guidance values, the present integrated safety review aimed to compile all the relevant preclinical toxicological studies and to combine them with substantial evidence gathered from the clinical paediatric use as part of the weight of evidence supporting the safety in young infants below 12weeks of age. LBG was demonstrated to have very low toxicity in preclinical studies mainly resulting from its indigestible nature leading to negligible systemic bioavailability and only possibly influencing tolerance. A standard therapeutic level of 0.5g/100mL in thickened infant formula is shown to confer a sufficiently protective Margin of Safety. LBG was not associated with any adverse toxic or nutritional effects in healthy term infants, while there are limited case-reports of possible adverse effects in preterms receiving the thickener inappropriately. Altogether, it can be concluded that LBG is safe for its intended therapeutic use in term-born infants to treat uncomplicated regurgitation from birth onwards.

Purpose Thickened infant formulas reduce regurgitation frequency and volume. Because the digestive tolerance of locust bean gum-containing formulas is controversial, the effectiveness and tolerance of a locust bean gum-thickened formula in infants presenting with regurgitation was evaluated. No other interventions were allowed during the 1 month follow-up period. Methods We conducted an open, prospective, observational study of a locust bean gum-thickened formula administered to infants presenting with moderate to severe regurgitation according to parents during 1 month. Effectiveness and tolerance were assessed by evaluating gastrointestinal symptoms and quality of life indicators. Results A total of 2,604 infants with an average age of 9.3±4.3 weeks were included in this 1 month trial. Regurgitation frequency and estimated volume decreased significantly ( p <0.001) and the episodes were resolved completely in 48% of the infants. A significant decrease in duration of crying and episodes of gas ( p <0.001), with improvement in quality of life parameters, was observed. Stool frequency increased and stool consistency softened ( p <0.001) to levels within the physiologic range, consistent with the increased fiber load (0.42 g/100 mL). Conclusion Locust bean gum-thickened formula decreased infant regurgitation, was well tolerated, and improved parental quality of life. Stool composition and frequency of the infants remained within the physiologic range.

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During the development of international standards by the Codex Alimentarius Commission, infant foods and their constituent ingredients are subject to rigorous risk analysis and are strictly regulated by many authorities. Various jurisdictions have approved only a limited number of additives specifically with regard to infant foods to fulfill specific technical requirements of quality. As part of the approval process, a rigorous safety assessment is essential to confirm that the use of additives does not pose any health risk for the consumer. An acceptable daily intake (ADI) may be derived from the toxicological databases. However, the ADI may not be applicable to infants because of the possible developmental sensitivities and potentially high exposure scenarios, leading to possible lower margins of safety than would often be determined for adult populations. There is interest in defining better food safety assessment approaches for pre-weaned infants aged less than 12-16 weeks. To confirm safe use in infants, we reviewed the suitability of the existing safety databases of six additives with historical uses in infant nutrition products. To determine further toxicity testing strategies, it is necessary to understand whether the chemical used in the additives is identical to endogenous physiological metabolites and/or whether immature organs of infants are targets of toxicity. Combined with an in-depth review of the existing relevant toxicological and nutritional studies, this integrated approach will facilitate decision-making. We propose a decision tree as a tool within this approach to help guide appropriate data requirements and identify data gaps. In cases of reasonable uncertainty, studies of targeted juvenile should be considered to investigate the safe use levels in food products.