Barriers to the use of toxicogenomics data in human health risk assessment: A survey of Canadian risk assessors
Introduction
Regulatory agencies worldwide have to adapt and improve human health risk assessment (HHRA) methods to meet challenges of the 21st century: a rapid increase in the number of chemicals to be assessed (in 2009, 87% of chemicals on the market lacked toxicity data) (Hartung, 2009), and the need for faster, more scientifically robust assessments. As such, they are encouraging the use of data generated by toxicogenomics technologies (Tralau and Luch, 2015). Large-scale programs aimed at exploiting toxicogenomics data in HHRA include the U.S. Environmental Protection Agency's (EPA) Tox21 (http://epa.gov/ncct/Tox21) launched after the publication of the National Research Council's (NRC) report Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007a). Besides, the SEURAT-1 research initiative was launched to develop alternative methods to replace animal testing of cosmetic products in the European Union (Gocht and Schwarz, 2015). Health Canada also began reflecting on this matter (CCA, 2012).
The potential of toxicogenomics in improving the HHRA process was recently examined in the literature (Bourdon-Lacombe et al., 2015, Chepelev et al., 2015, Goetz et al., 2011, Marx-Stoelting et al., 2015, McHale et al., 2010) and in various case studies (Bourdon et al., 2013, Burgoon et al., 2016, Euling et al., 2013, Moffat et al., 2015, Thomas et al., 2012, Wilson et al., 2013). Those studies showed that toxicogenomics research could be valuable at different stages of HHRA. First, toxicogenomics data can help in the hazard identification and characterization stages by facilitating the identification of mechanisms of action and allowing better in vitro to in vivo extrapolation and inter-/intra-species comparison. Secondly, toxicogenomics data can also contribute to the characterization of low-dose responses and thresholds, and help to investigate the transition between adaptive and toxic responses (Boverhof et al., 2011). Lastly, another significant advantage of toxicogenomics is the potential decrease in time and resources needed to generate toxicity data, compared to conventional testing on whole animals (NRC, 2007b).
Despite this strong interest from regulatory agencies, the use of toxicogenomics in HHRA remains very limited. For instance, in Canada, Bourdon-Lacombe et al. (2015) reported that between 2000 and 2013, only 2% of the evaluation from Health Canada Existing Substances Risk Assessment Bureau contained genomics information, and none in Canadian Drinking Water Quality programs (Bourdon-Lacombe et al., 2015). In the U.S., this proportion increases to 20% for EPA's Integrated Risk Information System (IRIS) program (Bourdon-Lacombe et al., 2015). Only a few authors have investigated the reasons for this limited use of toxicogenomics data by human health risk assessors. Potential barriers have been postulated, such as: difficulty in interpreting toxicogenomics data (Goetz et al., 2011, McHale et al., 2010, Pettit et al., 2010), lack of training or insufficient knowledge in risk assessors, dearth of standards and guidelines for toxicogenomics data quality assessment or proper application in HHRA (Bourdon-Lacombe et al., 2015, Euling et al., 2013, Goetz et al., 2011, Moffat et al., 2015, Pettit et al., 2010, Sturla et al., 2014, Tong et al., 2015), uncertainties regarding the utility of toxicogenomics in HHRA (Goetz et al., 2011, Pettit et al., 2010), and availability of toxicogenomics data (Chepelev et al., 2015, Euling et al., 2013, Moffat et al., 2015). However, very few studies have investigated these barriers systematically. Therefore, a more comprehensive and systematic scrutiny is needed.
One of those investigations surveyed mainly U.S. scientists regarding current and future use of toxicogenomics in risk assessment, as well as barriers to such a use (Pettit et al., 2010). However, it targeted scientists and decision-makers already involved in the field of toxicogenomics. Moreover, few respondents were from outside the U.S., leaving other countries, such as Canada, underrepresented. In order to fill this gap, a national survey was designed with the objectives of characterizing: 1) the current and future use of toxicogenomics data by Canadian human health risk assessors, 2) their knowledge of toxicogenomics, 3) their perceptions of the usefulness and potential impact of toxicogenomics on HHRA, and 4) the factors impeding the use of toxicogenomics data in HHRA in Canada.
Section snippets
Summary of methods
The complete methodology is described in the supplementary material. Briefly, an online questionnaire accessed through and completed on the FluidSurveys™ platform (http://fluidsurveys.com, Ottawa, ON, Canada) was designed based on a literature review of the topic (e.g. Bourdon-Lacombe et al., 2015, Boverhof et al., 2011, Chepelev et al., 2015, Goetz et al., 2011, Marx-Stoelting et al., 2015, McHale et al., 2010, Tong et al., 2015) and consultation with experts. To identify potential
Response rate
On a total of 39 questionnaires returned, 29 questionnaires were used for the analysis. Others were incomplete or not eligible. The response rate was difficult to ascertain because of recruitment methods, but would probably be less than 15%.
This sample is rather small, despite our recruitment efforts. The absence of a central list of Canadian human health risk assessors and the time constraints on the survey duration might have led to a possible selection bias which increased uncertainties
Conclusion
The use of toxicogenomics data in HHRA has the potential to better protect human populations from environmental exposure to toxicants through significantly improving the quality of HHRA conducted. This survey showed that human health risk assessors are quite positive about the use of toxicogenomics data in HHRA. However, its use in Canadian HHRA is very limited. This seems to be due in great part to: 1) human health risk assessors' lack of knowledge of toxicogenomics, 2) absence of guidelines
Declaration of interest
The authors' affiliations are shown on the cover page. They declare they have no conflict of interest.
Authorship contributions
This work was undertaken as part of JV's master's degree in community health at Université Laval, under the supervision of PL and CC. JV prepared the study, conducted the data collection and analysis, and wrote the manuscript. PL and CC contributed to the design, analysis and interpretation of the data, and to the writing of the final manuscript. MJR and MAS contributed to the development of the original protocol and did a critical review of the draft manuscript.
Funding
This work was supported by Fonds de Recherche du Québec - Nature et Technologies [Grant No. 174533].
Supplementary material
Supplemental details on the complete methodology and additional results (Tables S1–S3, Fig. S1) are available in the supplementary material. English and French copies of the survey administered in this study are also available as supplementary material.
Acknowledgements
The authors are thankful to Society of Toxicology of Canada (STC) and the Chapitre Saint-Laurent for their contribution to study recruitment. They also thank Reza Farmahin and Nikolai L. Chepelev of Health Canada for their review and comments on survey questions.
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