Q: Dow says that they are committed to understanding the possible risks of their products. But most of their tests are conducted on single chemicals, when everyone knows we’re exposed to a sea of chemicals — mixtures of chemicals — every day. Aren’t these mixtures more dangerous than the single chemicals?
A: Existing research indicates that mixtures of chemicals are unlikely to cause adverse effects when all of the individual chemicals are at safe levels. Dow therefore considers that a single chemical risk assessment approach – as required by existing regulatory schemes - is in most cases sufficiently protective of human health and the environment. However, in situations where screening assessments identify exceptions to this general rule, Dow supports the use of cumulative risk assessments to further evaluate the safety of the combination of chemicals. In fact, Dow researchers have contributed new methods to the scientific community to help prioritize mixtures for more detailed evaluation so that resources are applied where they are needed most.
Background
Humans have been exposed to the effects of combinations of chemicals (so-called ‘mixtures’) from the beginning of our existence. The food we eat, the air we breathe, and the products which we come into contact with every day are complex mixtures containing various man-made and naturally occurring chemicals. Nonetheless, chemical safety for the majority of chemicals has been based on the evaluation of single chemicals for a variety of reasons including the infinitely large number of possible chemical combinations, which would make a complete description of individuals’ exposures difficult if not impossible to determine and would include many compounds with little or no toxicity. Ongoing questions about the potential toxicity of mixtures (also referred to as ‘cumulative risk’) have resulted in governments in the EU and North America addressing whether existing regulation is sufficient, and considering suitable alternatives.
Dow Commitment
For several years, Dow has been engaged in advancing science-based approaches to assess the potential effects of combined exposure to multiple chemicals, including addressing the question of potential additive and synergistic effects of chemicals. This has led to Dow scientists developing new tools and frameworks to assess mixtures, including the Maximum Cumulative Ratio (MCR) screening tool. The use of the MCR screening tool - using basic exposure data and very cautious default assumptions (e.g., dose additivity) - enables the identification of those mixtures of greatest concern for which a cumulative risk assessment would be needed. The MCR provides guidance on a mixture’s toxicity, or the cumulative risk missed by a single chemicals risk assessment approach. The MCR values also indicate the fraction of toxicity that comes from the most toxic component of the mixture.
In addition to the MCR screening tool, Dow has contributed to the science of mixture toxicity by developing economical designs for mixtures investigations including mixtures statistics, and cell culture techniques. Dow is currently working with various academic and industry organizations to apply the MCR approach to investigate real-world mixtures of chemicals to identify when exposure to mixtures of chemicals are a concern. The entire suite of tools has been organized into a tiered “Decision Tree” framework by the European Chemical Industry Association (Cefic). Dow continues to share the work on the MCR and on the Decision Tree framework with industry, government and other stakeholders in various science and policy forums.
Dow Position
Based on research conducted to date, it appears that the toxicity of many mixtures encountered by individuals in the real world is usually driven by one or just a few chemicals within the mixture.
Furthermore, it also seems that the toxicity of mixtures which pose harm to human health and/or to the environment, appear to be driven by the toxicity of a single chemical within the mixture. Based on these findings, it is possible to take targeted action on the individual chemical posing the problem, rather than attempting to take action on a multitude of potentially harmless substances.
In summary, Dow considers that combined effects are unlikely when all of the chemicals of the mixture are at safe levels, which is often the case in real-world mixtures. Consequently Dow believes, as a general rule, a single chemical and source by source risk assessment approach to be an effective means for identifying the drivers of risk of a mixture. Dow also believes that existing regulations – such as EU REACH or global Plant Protection Regulations, which utilize large safety factors to keep exposure low - are sufficiently protective of human health and the environment. In those cases where tiered screening assessments such as the MCR identify exceptions to this general rule, a cumulative risk assessment should be used to further evaluate the safety of the mixture.
Further Information
Below is a listing of selected Dow publications on this topic.
- Paul S. Price and Xianglu Han (2011). Maximum Cumulative Ratio (MCR): A Tool for Assessing the Value of Performing a Cumulative Risk Assessment, International Journal of Environmental Research and Public Health 8: 2212-2225; doi:10.3390/ijerph8062212
- Boobis A, Budinsky R, Collie S, Crofton K, Embry M, Felter S, Hertzberg R, Kopp D, Mihlan G, Mumtaz M, Price P, Solomon K, Teuschler L, Yang R, Zaleski R. (2011). Critical analysis of literature on low-dose synergy for use in screening chemical mixtures for risk assessment. Crit Rev Toxicol. 41:369-83.
- P.S. Price. Synergy a Risk Management Perspective. In The Principles and Practice of Mixtures Toxicology. Wiley-VCH. Ed. Moiz Mumtaz, 2010
- Carney, E.W., Woodburn, K. and Rowlands, J.C. (2010). Endocrine Active Chemicals. In: Principles and Practice of Mixtures Toxicology. Mumtaz, M. (ed.). Wiley-VCH Verlag GmbH & Co. KGaA, Germany. pp. 421-442.
- Price PS, Hollnagel HM, Zabik JM (2009). Characterizing the noncancer toxicity of mixtures using concepts from the TTC and quantitative models of uncertainty in mixture toxicity. Risk Analysis 29:1534-48.
- Price P, Wiltshire G. (2009). Modelling the chronic non-cancer effects of mixtures of migrants using Cramer classes and quantitative models of uncertainty. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 26:1547-55.
- Stork, L.G., Gennings, C., Carter, W.H. Jr., Teuschler, L.K. and Carney, E.W. (2008). Empirical evaluation of sufficient similarity in dose-response for environmental risk assessment of chemical mixtures. J. Agric. Biol. Environ. Statistics 13:313-333.
- Charles, G.D., Gennings, C., Tornesi, B., Kan, L., Zacharewski., T.R., Gollapudi, B.B. and Carney, E.W. (2007). Analysis of the interaction of phytoestrogens and synthetic chemicals: An in vitro/in vivo comparison. Toxicol. Appl. Pharmacol. 218:280-288.
- Teuschler, L., Klaunig, J., Carney, E., Chambers, J., Conolly, R., Gennings, C., Giesy, J., Hertzberg, R., Klaassen, C., Kodell, R., Paustenbach, D. and Yang, R. (2002). Support of science-based decisions concerning the evaluation of the toxicology of mixtures: a new beginning. Reg. Toxicol. Pharmacol. 36:34-39.