The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages between endpoints. We discuss how the distinction between quantal and graded endpoints and the type of linkage between endpoints can guide model design and selection. Strengths and limitations of two main approaches and possible ways forward are outlined.

BackgroundPreterm birth is a risk for cognitive development. This study assessed the cognitive profile of children born very preterm at the age of 11 years as well as the associated risk factors.MethodsA total of 128 children born very preterm were included. Magnetic resonance imaging was performed at term age. Cognitive development was assessed using the full-scale intelligence quotient (IQ) and four domains of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), Finnish translation. The results were compared with test norms.ResultsMost study children performed at average (51%) or low average (21%) levels in the full-scale IQ assessment. The correlation between 5- and 11-year full-scale IQ was 0.73 (P<0.001). Compared with the normative data, children born very preterm performed poorer in all domains of the cognitive profile. The only significant risk factor for poor general cognition was major brain pathology. When considering all four domains of WISC-IV, low paternal education, male gender, and low birth weight z score were also found to be significant risk factors.ConclusionsLess than one-third of the children born very preterm performed below the low average cognitive level at 11 years of age. Specific neonatal and sociodemographic risk factors were identified as affecting the cognitive profile.

Because aquatic macroinvertebrates may be exposed regularly to pesticides in edge-of-the-field water bodies, an accurate assessment of potential adverse effects and subsequent population recovery is essential. Standard effect risk assessment tools are not able to fully address the complexities arising from multiple exposure patterns, nor can they properly address the population recovery process. In the present study, we developed an individual-based model of the freshwater amphipod Gammarus pulex to evaluate the consequences of exposure to 4 compounds with different modes of action on individual survival and population recovery. Effects on survival were calculated using concentration-effect relationships and the threshold damage model (TDM), which accounts for detailed processes of toxicokinetics and toxicodynamics. Delayed effects as calculated by the TDM had a significant impact on individual survival and population recovery. We also evaluated the standard assessment of effects after short-term exposures using the 96-h concentration-effect model and the TDM, which was conservative for very short-term exposure. An integration of a TKTD submodel with a population model can be used to explore the ecological relevance of ecotoxicity endpoints in different exposure environments.