- action plan
- case reports
- chemical industry
- chemical risk assessment
- chemical safety
- clear framework
- data quality
- epidemiological studies
- European Commission’s Institute of Health and Consumer Protection
- existing information sources
- good exposure assessment practice
- good human data collection practice
- good risk assessment practice
- human data
- International Programme on Chemical Safety
- null epidemiologic data
- poisons centre records
- Risk assessment
- self-administered surveys
- Use of Human Data in Risk Assessment
WR 05 : Alternative Testing Approaches in Environmental Risk Assessment | February 2005
This 2-day workshop, sponsored and organised by ECETOC, co-sponsored by ECVAM and Cefic LRI, took place at Crécy-la-Chapelle, near Paris, on July 7-9, 2004.
The aim of the workshop was to facilitate an active dialogue amongst industry, regulators and academia on the pragmatic use of alternative approaches to animal testing. The workshop addressed in vivo, in vitro and in silico approaches, in line with the 3Rs (Replacement, Refinement and Reduction), for the generation of hazard and exposure information within the context of environmental risk assessment.
There were 37 attendees, with people from academia, industry as well as the regulatory community. Appendices 1 and 2 give the full list of attendees and the meeting programme.
The primary outcome of the meeting was the development of research networks/programmes to develop alternative methodologies to address the environmental safety of chemicals.
The workshop first identified methodology for generating information for environmental risk assessment, in line with the 3Rs. Then it identified research to address knowledge gaps in the proposed methodology and finally drafted research plans including potential funding opportunities, collaborations and timelines.
The workshop was very successful in that everyone present expressed their desire to remain in contact, developing the research needs and participating in networks.
Assessing the effect of chemicals on fish
There were a number of issues raised and one key question was whether it was necessary to test fish for acute effects. Thus while approaches for limiting fish numbers (e.g. the step-down approach) were seen as helpful, they may prove to be redundant if other species (with or without Quantitative Structure Activity Relationship (QSAR) support) prove to be sufficiently protective when addressing acute effects in the early stages of assessing environmental safety.
The key areas of research identified were development of fish embryo, fish cell line tests and (Q)SARs.
i) Fish embryo test – This requires research into the acceptability of embryonic tests as non-animal alternatives and into cross species differences (in applicability as well as sensitivity). This is seen as a crucial issue, as there will be limited benefit developing an alternative method that would not be acceptable to all regulators, including those in other regions than Europe, and for whom fish acute tests would then have to be conducted. Future innovative research on genomic and proteomic developments might offer mechanism-related approaches in the fish embryo model for hazard and risk assessment. These could later be linked to cellular developments (see ii).
ii) Fish cell lines ? The aim of this research would be to investigate whether a battery of fish cell toxicity tests could be used as a screening test. In the longer term such research should address whether fish cells toxicity would be sensitive and accurate enough to replace fish in vivo tests.
iii) (Q)SAR – These need further development, establishing which of the current models are useful, their domain and extending the models to cover more specifically acting chemicals. There was also a clear message that more knowledge was needed to address the mechanisms of effects in fish. In this context, the research into fish embryo and cell toxicity tests could be useful.
Assessing the fate of chemicals in fish (bioconcentration)
Two strategies for addressing chemicals for a ‘B’ assessment were developed. The first approach was developed to address groups of chemicals when a definitive value is not required, but a value less than some pre-agreed bright-line. Such an approach, for example in the context of the EU-PBT strategy, could lead to significant reduction in the number of chemicals tested. This approach starts by identifying the chemicals within a group. This may be based on similar chemical structures or presumed bioconcentration behaviour. The purpose of the grouping would be to allow for key members of the group to be identified and tested. Interpolation within the group would then allow for bioconcentration factor (BCF) values to be assigned to the other group members via a local QSAR. The second strategy, a single chemical approach, starts with a worst-case assumption and then allows further refinement depending upon subsequent actions. Several of the alternative approaches discussed in the workshop could help move a chemical through the proposed scheme (see Figure 1).
There were four main alternatives addressed, which could be further developed to form research projects.
i) OECD 305 – the standard in vivo method assessing the bioconcentration potential of a chemical in fish needs investigation to clearly identify uncertainties in measurements derived by this protocol and clarifying its domain of application.
ii) Other in vivo experimental approaches, e.g. the dietary biomagnification factor (BMF) protocol and abbreviated OECD 305, need to be further investigated to define and possibly extend their domain and limits of applicability.
iii) In vitro assays, expert systems and models need further development and evaluation, especially those that are capable of incorporating absorption, distribution, metabolism, elimination, (ADME) concepts and physiology based pharmacokinetics (PBPK) modelling.
iv) Finally the ADME processes involved in bioconcentration need further research. The workshop addressed the key processes and identified research priorities, including the establishment of a gold standard database of BCF values and a review of available data concerning the potential for chemicals to degrade or be metabolised, both valuable short-term projects.