The Grouping and Assessment Strategy for Organic Pigments (GRAPE): Scientific evidence to facilitate regulatory decision-making.

This article presents the Grouping and Assessment Strategy for Organic Pigments (GRAPE). GRAPE is driven by the hypotheses that low (bio)dissolution and low permeability indicate absence of systemic bioavailability and hence no systemic toxicity potential upon oral exposure, and, for inhalation exposure, that low (bio)dissolution (and absence of surface reactivity, dispersibility and in vitro effects) indicate that the organic pigment is a 'poorly soluble particle without intrinsic toxicity potential'. In GRAPE Tier 1, (bio)solubility and (bio)dissolution are assessed, and in Tier 2, in vitro Caco-2 permeability and in vitro alveolar macrophage activation. Thereafter, organic pigments are grouped by common properties (further considering structural similarity depending on the regulatory requirements). In Tier 3, absence of systemic bioavailability is verified by limited in vivo screening (rat 28-day oral and 5-day inhalation toxicity studies). If Tier 3 confirms no (or only very low) systemic bioavailability, all higher-tier endpoint-specific animal testing is scientifically not-relevant. Application of the GRAPE can serve to reduce animal testing needs for all but few representative organic pigments within a group. GRAPE stands in line with the EU REACH Regulation (Registration, Evaluation, Authorisation and Restriction of Chemicals). An ongoing research project aims at establishing a proof-of-concept of the GRAPE.