Expected Risk as basis for assessment of safe use of chemicals

This paper describes a straightforward modeling procedure to derive ‘expected risk’ (ER) of chemical substances. Starting from proposed use volumes, intended uses, physical and chemical substance properties and toxicity information, the procedure combines multimedia environmental fate modeling with species sensitivity modeling to derive the probability that exposure concentrations exceed critical effect concentrations. The procedure was tested on 1977 so-called mono-constituent organic chemicals that had been registered to be marketed in the EU, after ‘possibility to be used safely’ had been demonstrated by showing that the possible Risk Quotients (RQ) defined as PEC/PNEC ratios (Predicted Exposure Concentration & Predicted No Effect Concentration) were expected to remain below the value of 1, as required by REACH. It appears from this study that (i) RQ and ER of chemicals can be calculated readily, reliably, transparently and reproducibly, that (ii) both RQ and ER can be used to assess whether a new chemical may exceed a chosen acceptability level, but that (iii) in addition ER can be straightforwardly used to rank chemicals according to expected environmental safety. In conclusion, the paper states that modeling ER of chemicals (instead of estimating RQ values), could strengthen the scientific basis of environmental risk assessment for use in REACH. The paper further recommends that more robust environmental risk calculation can be done by using acute EC50, instead of chronic NOEC as critical effect concentration

Development of a solid-phase passive dosing system for polycyclic aromatic hydrocarbons in fish cell cytotoxicity assays

Traditionally, sparingly soluble and volatile test chemicals are added to cell assays via a carrier solvent and corresponding dose response curves are based on nominal concentrations. However, toxicity, as measured by these cell assays, may be unreliable. Carrier solvents may elicit (in)direct effects on the cells. Moreover, actual and nominal toxicant concentrations may be significantly different due to extra-cellular sorption, precipitation, volatilization or degradation of the chemical. In this study, an alternative passive diffusion method for dosing sparingly soluble and volatile chemicals in cell assays was developed. Poly(dimethylsiloxane) disks were loaded with a suite of polycyclic aromatic hydrocarbons (PAHs, log Kow ranging from 4-6) via a spiked methanol/water solution. The disks were subsequently introduced into the well of a 24-well microtitre plate containing cell culture medium and inserts on which rainbow trout liver cells, RTL-W1, were grown. The PAHs were allowed to diffuse from the PDMS disks into the medium to dose the cell system for 48 hours. Equilibrium between PDMS and medium concentrations were established for PAHs with a wide range of hydrophobicity within 24 hours. Cytotoxicity, measured using the CFDA-AM, alamar blue, neutral red uptake, and the induction of cytochrome CYP1A, measured as 7-ethoxyresorufin-O-deethylase (EROD) activity, were used as biological endpoints. Mass balance indicated that the loss of PAHs from PDMS to medium was negligible, suggesting the disks had sufficient capacity to compensate for losses of the test chemical. Cytotoxicity and EROD activity were found to be consistent and comparable to conventional dosing methods. Lastly, PDMS and medium concentrations, estimated using PDMS to methanol/water, PDMS to medium and serum to medium partition coefficients, fit measured concentrations

Evaluating solid phase (micro-) extraction tools to analyze freely ionizable and permanently charged cationic surfactants

Working with and analysis of cationic surfactants can be problematic since aqueous concentrations are difficult to control, both when taking environmental aqueous samples as well as performing laboratory work with spiked concentrations. For a selection of 32 amine based cationic surfactants (including C8- to C18-alkylamines, C14-dialkyldimethylammonium, C8-tetraalkylammonium, benzalkonium and pyridinium compounds), the extraction from aqueous samples was studied in detail. Aqueous concentrations were determined using solid phase extraction (SPE; 3 mL/60 mg Oasis WCX-SPE cartridges) with recoveries of ≥80% for 30 compounds, and ≥90% for 16 compounds. Sorption to glassware was evaluated in 120 mL flasks, 40 mL vials and 1.5 mL autosampler vials, using 15 mM NaCl, where the glass binding of simple primary amines and quaternary ammonium compounds increased with alkyl chain length. Sorption to the outside of pipette tips (≤20% of total amount in solution) when sampling aqueous solutions may interfere with accurate measurements. Polyacrylate solid phase microextraction (PA-SPME) fibers with two coating thicknesses (7 and 35 μm) were tested as potential extraction devices. The uptake kinetics, pH-dependence and influence of ionic strength on sorption to PA fibers were studied. Changing medium from 100 mM Na+ to 10 mM Ca2+ decreases Kfw with one order of magnitude. Results indicate that for PA-SPME neutral amines are absorbed rather than adsorbed, although the exact sorption mechanism remains to be elucidated. Further research remains necessary to establish a definitive applicability domain for PA-SPME. However, results indicate that alkyl chain lengths ≥14 carbon atoms and multiple alkyl chains become problematic. A calibration curve should always be measured together with the samples. In conclusion, it seems that for amine based surfactants PA-SPME does not provide the reliability and reproducibility necessary for precise sorption experiments, specifically for alkyl chain lengths beyond 12 carbon atoms

Risk Assessment Acknowledging Variability in Both Exposure and Effect

Risk assessment provides a scientific basis for evaluating potentially toxic chemicals. Central in the concept of risk is its dependence on both exposure and toxicity. Chemicals will only express their toxicity when these exceed a concentration at which a defined target becomes affected. While this is a trivial remark among environmental risk assessors, the new chemicals policy of the EU tends to divert into a different direction. The communication of the European Commission on its new Chemicals Policy places an emphasis on hazard-based chemical management. We urge the Commission to reconsider this view. We believe that for the majority of chemicals evaluated under REACH, a scientifically sound risk assessment evaluating both exposure and effect should remain the core of the EU strategy “towards a toxic-free environment”

Expected Risk as basis for assessment of safe use of chemicals

This paper describes a straightforward modeling procedure to derive ‘expected risk’ (ER) of chemical substances. Starting from proposed use volumes, intended uses, physical and chemical substance properties and toxicity information, the procedure combines multimedia environmental fate modeling with species sensitivity modeling to derive the probability that exposure concentrations exceed critical effect concentrations. The procedure was tested on 1977 so-called mono-constituent organic chemicals that had been registered to be marketed in the EU, after ‘possibility to be used safely’ had been demonstrated by showing that the possible Risk Quotients (RQ) defined as PEC/PNEC ratios (Predicted Exposure Concentration & Predicted No Effect Concentration) were expected to remain below the value of 1, as required by REACH. It appears from this study that (i) RQ and ER of chemicals can be calculated readily, reliably, transparently and reproducibly, that (ii) both RQ and ER can be used to assess whether a new chemical may exceed a chosen acceptability level, but that (iii) in addition ER can be straightforwardly used to rank chemicals according to expected environmental safety. In conclusion, the paper states that modeling ER of chemicals (instead of estimating RQ values), could strengthen the scientific basis of environmental risk assessment for use in REACH. The paper further recommends that more robust environmental risk calculation can be done by using acute EC50, instead of chronic NOEC as critical effect concentration