Letter to the editor RE: Wolf et al.¹

Sir,

Wolf et al. (2016) used the RISK21 webtool application (RISK21) to demonstrate, compare, and prioritize an evaluation of 20 chemicals in drinking water. Toluene diisocyanate (TDI; CAS 26471–62-5) and two other chemicals were designated as “high priority.” This letter further refines the exposure estimates for TDI based on additional insight into the physical–chemical properties, as well as publicly available and reliable information. Lower-tier evaluations reported in Wolf et al. (2016) used a water solubility value generated by modeling software (EPIWIN) to drive the exposure estimate. This approach is inappropriate for hydrolytically unstable substances, such as TDI. In aqueous media, isocyanates such as TDI only have a transient existence of seconds to minutes (Yakabe et al. 1999). The European Chemicals Agency (ECHA) (2016) has stated …a water solubility value for TDI is a notional concept and has little or no relevance to environmental partition processes. Given this information and given that RISK21 is “exposure-driven,” we offer a more suitable estimate of potential environmental exposure concentration in water for TDI and use the Threshold of Toxicological Concern (TTC) approach embodied in the RISK21 Roadmap to demonstrate a more appropriate assessment of human health risk.

A more appropriate method to estimate TDI exposure concentrations in water for use in the RISK21 webtool is to leverage the publicly available freshwater Regional Predicted Exposure Concentration (PEC) value (Bureau for Chemical Substances 2013). In comparison to the PEC (local), the PEC (regional) incorporates all potential exposure scenarios, and thus represents a very conservative approach for estimating drinking water concentrations. The PEC was derived using the European Union System for the Evaluation of Substances (EUSES²) software. Using physical/chemical parameters and tonnage information in the REACH dossier, an estimated worst case freshwater exposure concentration (i.e. PEC (regional) value; a surrogate for drinking water) of 4.14E-08 mg TDI/L was generated. Using this PEC value and assuming 2 L water intake per day for a 60 kg adult (World Health Organization 2008), the revised exposure estimate for use in the RISK21 webtool is 1.38E-09 mg TDI/kg-d [(4.14E-08 mg/L * 2 L/day)/60 kg =1.38E-09 mg/kg-d].

A TTC versus Exposure Concentration plot using the refined exposure estimate is provided in Figure 1. Values to the left of the Structural Alert line are considered to be of a low priority. Thus, using the more appropriately derived exposure concentration for TDI results in an evaluation, which clearly indicates TDI (long-dash) is of low priority. Therefore, as with other chemicals that were eliminated as potential concerns, a further, higher tier evaluation that compares exposure to toxicity is unnecessary.

Figure 1. TTC/Exposure Plot comparing potential TDI exposure values described in Wolf et al. (2016) with revised exposure values generated using the Regional PEC. The dotted line [TDI (Wolfe et al. 2016)] used an exposure estimate of 0.8 mg/kg-d, while the long-dash line [TDI (Regional PEC)] is a revised exposure estimate of value of 1.38E-09 mg/kg-d. The default TTC value of 2.5E-6 mg/k-d for a Structural Alert (solid line) was used.

In conclusion, the RISK21 webtool is designed for users to interactively explore the intersection of exposure and toxicity and evaluate the risk matrix in a graphical form. The characterization of potential TDI exposure has been refined and improved to reflect not only the transient presence of TDI in water, but also the use of transparent, publicly available data. As a result of the updated characterization, TDI would now be placed in the “no concern” category in the comparison exercise conducted by Wolf et al. (2016).

Declaration of interest

AHC, MWS and BT are employed by the International Isocyanate Institute (III), a not-for-profit scientific research organization whose members are diisocyanates producers. The authors have sole responsibility for the content of the letter; the interpretation and views expressed in the letter are not necessarily those of the III. None of the authors recently or is currently involved as an expert witness in litigation or formal government rulemaking on the subject of this article.

Notes

Notes

1 Illustrative Case Using the RISK21 Roadmap and Matrix: Prioritization for Evaluation of Chemicals Found in Drinking Water. 2016, Crit. Rev. Toxicol. 46: 43–53.

2 https://ec.europa.eu/jrc/en/scientific-tool/european-union-system-evaluation-substances