Use of guinea pig data to obtain starting points for skin sensitisation risk assessment - A commentary.

The increasing drive to understand the likelihood of skin sensitisation from plant protection products (PPPs) in workers and the general public has resulted in recent initiatives to establish a quantitative risk assessment (QRA) methodology applicable to these products and their exposure scenarios. The effective evaluation of skin sensitising substances requires not only the identification of that toxicological hazard, but also determination of relative sensitising potency. Typically, this has been achieved by interpretation of local lymph node assay (LLNA) dose response data, delivering what is known as the EC3 value. This permitted regulatory division of skin sensitisers into defined potency sub-categories, but more importantly enabled derivation of a no expected sensitisation induction level (NESIL) as the point of departure for QRA. However, for many existing substances there is no LLNA data, only older guinea pig results exist. To avoid additional (in vivo) testing, an approach has been outlined to employ guinea pig data and existing regulatory guidelines on the determination of potency sub-categorisation to provide a guinea pig based NESIL. The approach adopts a conservative extrapolation from LLNA NESIL benchmarks to deliver points of departure as the basis for the type of QRA process already in successful use by other industries.

Assessing the risk of induction of skin sensitization to plant protection products: A quantitative approach.

Exposure to skin sensitizers is common and regulated in many industry sectors. For cosmetics, a risk-based approach has been implemented, focused on preventing the induction of sensitization. First, a No Expected Sensitization Induction Level (NESIL) is derived, then modified by Sensitization Assessment Factors (SAFs) to derive an Acceptable Exposure Level (AEL). The AEL is used in risk assessment, being compared with an estimated exposure dose, specific to the exposure scenario. Since in Europe there is increased concern regarding exposure towards potentially sensitizing pesticides via spray drift, we explore how existing practice can be modified to allow Quantitative Risk Assessment (QRA) of pesticides for bystanders and residents. NESIL derivation by the Local Lymph Node Assay (LLNA), the globally required in vivo assay for this endpoint, is reviewed alongside consideration of appropriate SAFs. Using a case study, the principle that the NESIL in µg/cm2 can be derived by multiplying LLNA EC3% figure by a factor of 250 is adopted. The NESIL is then reduced by an overall SAF of 25 to establish an exposure level below which there is minimal bystander and resident risk. Whilst this paper focuses on European risk assessment and management, the approach is generic and universally applicable.

Fragrance allergy: assessing the risk from washed fabrics.

The prevalence of contact allergy to fragrance ingredients increased during the last part of the 20th century with the consequence that a substantial number of individuals are at risk of experiencing allergic contact dermatitis (ACD) if they have a sufficient degree of skin exposure to the chemical to which they have become sensitized. Such exposure does not necessarily have to arise from the type of source that originally induced the sensitization. A number of sources of exposure are clearly associated with risk of elicitation of ACD, but the role of fragrance deposited on fabrics, for example as a result of laundry processes, also can be questioned. In this article, firstly, the risk of the induction of fragrance-related ACD from exposure to fragrance via fabric is considered. Using a quantitative risk-assessment approach, the risk appears to be extremely low. The possibility that fragrance residues on laundered fabrics might elicit reactions in those already sensitized by a different route is also discussed. Clinically, clothing pattern dermatitis associated with fragrance allergy is almost never observed, although this could be investigated clinically by exposing sensitized individuals to the relevant fragrance allergen.