I. de Vries

Healthy volunteer studies in toxicology

In the future there will be an increasing need for quantitative human risk assessment in order to develop soundly-based risk level regulations. Human volunteer studies can contribute to gain essential data needed for this risk assessment. Volunteer studies are especially relevant to study the biokinetics and metabolism of a compound. Comparison of these data with those of laboratory animals can increase the accuracy in extrapolation study results from animals to man. Furthermore, the results of volunteer studies can be used to fill in the gaps of knowledge which cannot be solved with in vitro or animal studies in order to develop adequate physiologically-based biokinetic or biodynamic models for human risk assessment.

Prospective follow-up study on battery ingestion in children in the Netherlands

Purpose: In the 1990-2000s, several large North-American studies increased the awareness about the risks of button ingestion in children. Identified risk factors for severe complications were lithium-type button batteries, large diameter cells and age <4 years. We aimed to study the current frequency and circumstances of (severe) complications after battery ingestion in children in the Netherlands, in recent years. Methods: A prospective follow-up study was conducted in 2011-2015 at the Dutch Poisons Information Center (DPIC). All consecutive cases of battery ingestion in children <6 years were included. Follow-up was performed by using a standardized questionnaire, over the telephone. The primary outcome was the occurrence of major complications (i.e. severe symptoms and/or death). Results: During a 4-year period, 1026 cases of human battery exposure were reported to the DPIC (annual incidence of 15.3 potential battery ingestion per million population). N = 405 exposures in which the patient was <6 years and had ingested (witnessed or suspected) at least one battery, were included in the study. In 229 children (57%), a battery was detected (spontaneous passage, positive X-ray or endoscopic removal). Button batteries with a diameter <15 mm were most often involved (54% of the batteries). Batteries with a diameter ≥15 mm were more often located in the oesophagus/throat than batteries with a smaller diameter (p < 0.001). All button batteries with a diameter ≥15 mm located in the oesophagus/throat were endoscopically removed (N = 8). No severe complications or fatalities were reported; the confidence interval (CI) for the occurrence of a severe complication was [0%, 1.3%]. Local injury was noticed in 9 patients (3.9%; CI: [1.9, 7.6]). Conclusions: In this study, the annual incidence of battery ingestion per million population in the Netherlands is comparable to the North-American annual incidence reported between 1985 and 2009 (between 6.3 & 15.1). Batteries with a diameter ≥15 mm are more often located in the oesophagus/throat than batteries with a smaller diameter and therefore pose a higher risk for local injuries or severe complications. The frequency of occurrence of severe complications after battery ingestion in children is low, but not negligible.