Chinese Toxicological Alternatives and Translational Toxicology (TATT) 2018

TATT 2018 Special Session:

Use of New Approach Methods (NAM) in Next Generation Risk Assessments (NGRA)


Hajime Kojima (NIHS Japan), Matt Dent (Unilever), Paul Carmichael (Unilever), Maurice Whelan (JRC), Guo Jiabin (AMMS), Ellen Fritsche (IUF Leibniz) & Jin Li (Unilever)

Session Abstract

The International Cooperation on Cosmetics Regulation (ICCR) is an international group of regulatory authorities from Brazil, Canada, the European Union, Japan, and the United States. ICCR members work together to promote regulatory alignment, in order to maximize consumer protection while minimizing barriers to trade.

At the ICCR annual meeting, the Joint Regulators-Industry Working Group (JWG) issued its report ‘Integrated Strategies for Safety Assessments of Cosmetic Ingredients – Part I’ (ICCR, 2017). The purpose is to outline principles that underpin the integration of novel methods and data in an exposure-led approach for the safety assessment of cosmetic ingredients.

In brief, the document summarizes major overarching principles for incorporating new approach methodologies (NAM) into an integrated strategy for risk assessment of cosmetic ingredients (or Next Generation Risk Assessment: NGRA), along with examples showing their usefulness to safety evaluation. Part 2 of the ICCR Integrated Strategies for Safety Assessment of Cosmetic Ingredients JWG report is intended to provide some additional guidance to safety assessors on the types of NAM that may be used in an NGRA.

Indeed, in recent years there has been a lot of interest in the application of new approach methods (NAM) for toxicological safety assessment. The complete ban on animal testing for cosmetics in Europe and the Lautenberg Chemical Safety Act in the United States have provided strong incentives to develop alternative strategies, in line with the general paradigm change towards mechanistic-based risk assessment.  There are, however, very few successful examples of the use of NAM to support regulatory decisions.  To aid implementation of NAM into risk assessment, the ICCR convened scientists from regulatory authorities and industry to define the overarching principles that should guide the development of NGRA for cosmetic ingredients. These principles are the first joint articulation from scientists in regulatory agencies and industry on the use of NGRA in regulatory decisions.  They aim to achieve a common understanding of the goals, conduct, and documentation of NGRAs to facilitate their regulatory use. These principles, though more thoroughly considered for cosmetic ingredients, provide a path forward in the acceptance and implementation of NAM in safety decisions across sectors, including consumer products and chemical industries.  In this session we will discuss the ICCR principles for incorporation of NAM into risk assessment decisions and will present case studies from industry and government on the implementation of NAM in chemical safety decisions.  Presentations will focus on the practical application of NAM to current risk assessment issues and demonstrate the utility of NAM to support decision-making for product formulation and chemical regulation.   The presentations will be followed by a panel discussion on successful approaches that are being used in safety decision making and the challenges that remain as we seek to apply NGRA to risk-based decision-making more broadly.

TATT Special Session on Thursday October 11, 08:30-12:05

08:30                   An introduction to the ICCR and Principles for the Safety Assessment of Cosmetic Ingredients (Hajime Kolime) This presentation will report on the activities at the JWG of the ICCR and provide information on the Integrated Strategies for Safety Assessments of Cosmetic Ingredients.

08:50                   Implementation of the ICCR Principles and a case study in androgen receptor effects (Matt Dent). This presentation will provide an overview of the nine principles and their importance, including why it is important that NGRAs are human-relevant, exposure-led, hypothesis-driven and designed to prevent harm; conducted using a tiered and iterative approach using all the available data, using robust and relevant methods and strategies; and documented transparently, being clear about sources of uncertainty. A case study describing an example of NAM use in pre-regulatory decision making will be shown.

09:20                   Use of NAM in NGRA: Case studies from the consumer products Industry – teaming with the US-EPA to make decisions on safety (Paul Carmichael) This presentation will include data on number of case study chemicals, intended for use in theoretical product types, that have been generated to exemplify the use of NAM in NGRA decision making.

09:50                   Coffee break

10:10                  Building an NGRA for the green tea catechin EGCG (Ellen Fritsche) In this talk, investigations into the green tea catechin EGCG will be presented; how its effects map onto an AOP; and how dosimetry was used to estimate the biological relevance of in vitro findings with neurospheres, a unique NAM.

10:40                   Incorporating a tiered approach to characterise cellular stress pathways in an exposure-led framework for NGRA (Jiabin Guo) This presentation will introduce a tiered approach for investigating the effects of chemicals on cellular stress pathways, and will provide case studies that illustrate how identification of in vitro cell stress markers, enables an understanding of the relevance of ‘tipping points’ for adaptive/adverse responses in vivo.

11:10                  Establishing the scientific credibility of NAM for NGRA (Maurice Whelan) In order to gain regulatory acceptance and foster uptake of NAM for NGRA, it is imperative that efficient and effective means are devised to establish their scientific credibility. In particular, validation strategies need to be designed that fit with a NAM paradigm together with the proper engagement of decision makers.

11:40                   Panel discussion led by Jin Li

12:05                   Session ends

Poster Presentations

Towards next generation risk assessment: bridging in vitro points-of-departures to human safety assessment using physiologically-based pharmacokinetic modelling with dose metric considerations – a case study with doxorubicin. Authors: Hequn Li, Wenbo Xin, Jin Li, Haitao Yuan, Qiang Zhang, Alistair Middleton, Jie-Bing Zhu, Jiabin Guo, Shuangqing Peng