Exposure Science
At Unilever, we are committed to advancing NGRA by integrating cutting-edge modelling approaches that reduce reliance on animal testing while ensuring human and environmental safety. As with any toxicological safety assessment, our NGRA for human and environmental effects depend on a clear understanding of exposure: how people use our products, how much of an ingredient is absorbed during normal use, and its fate in the body, including during pregnancy. In addition, understanding environmental exposure is critical, as our ingredients are often disposed of down the drain after use.
Within our NGRA framework, exposure information for each chemical is considered using a tiered exposure approach. All ingredients undergo exposure assessment and a conclusion on safety can be reached using external exposure estimates alone for many substances. When it is crucial to understand the relationship between external and internal exposure for a chemical, we use exposure modelling, such as Physiologically Based Kinetic (PBK) and in vitro to in vivo extrapolation (IVIVE). The predicted internal exposure concentrations are used to interpret in vitro bioactivity data in animal-free safety decisions for humans and the environment (e.g., see additional details in our Systemic Safety and Environmental Safety pages).
External Exposure
Our approach begins with a comprehensive assessment of external exposure scenarios, including both consumer use and environmental external exposure. These scenarios are quantified using established exposure tools and approaches, such as by estimating the externally applied dose in humans of, for example, a personal care product type, and using modelling approaches to determine the amount of an ingredient that is expected to be present in the environment (see additional details in our Environmental Safety page).
This enables us to:
- Predict the extent of human exposure, including oral, dermal, and inhalation routes.
- Predict concentrations of our ingredients in different environmental compartments to understand risk to environmental species by, for example, comparison with the predicted internal exposure of those ingredients within an organism (such as fish).
Internal Exposure
One of the key pillars of the NGRA strategy is the use of PBK modelling to translate external exposure into internal concentrations within the target species (e.g., the body of a human or a fish).
This enables us to:
- Predict human internal dose metrics such as plasma concentrations of cosmetic ingredients (e.g., Cmax) using non-animal methods derived parameters for topically applied chemicals, e.g., benzophenone-4 and other highly protein-bound UV filters;
- Compare internal exposure levels with in vitro bioactivity data, as shown through individual case studies (coumarin and benzophenone-4) and broader investigations (70 consumer exposure scenarios) to ensure that safety decisions provide protection equivalent to or exceeding that offered by traditional animal testing;
- Support regulatory submissions and safety assessments without animal testing. Use in vitro-to-in vivo models to convert in‑vitro test results into estimates of the chemical levels in the environment that would cause similar levels inside a living fish, e.g., in case studies involving 2-Hydroxy-4-methylbenzophenone, retinoic acid and other chemicals exposed to Zebrafish cell lines.
- Develop toxicokinetic models that can predict steady-state concentration ratios (internal/external) within aquatic species (vertebrates & invertebrates) for a range of chemicals to help predict and understand the potential for bioaccumulation of chemicals in the aquatic species environment (PDF 549.24 KB).
