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Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as "positive" or "negative" in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma C max . We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the C max at a dose level that produced significant teratogenicity or embryolethality, the negative being the C max at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no-effect level for all positive compounds, and the negative exposure list contains C max values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure-based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment.

A meeting was convened so that users of three models for in vitro developmental toxicity (embryonic stem cells, whole embryo culture, and zebrafish) could share their experiences with each model, and explore the areas for improvement. We present a summary of this meeting and the recommendations of the group.

Thresholds in UA blood for pH, pCO2, sO2 and BE(oxy.) in term-infants are: 7.000, 84 mmHg, 3.0 % and - 20 mmol/l, respectively. Delivery of an otherwise healthy baby without getting in touch with these thresholds seems to be safe both for the baby and the obstetrician. In addition, severe neonatal depression (Apgar 1 min: 0 and 1) is usually avoided (0 / 398). BE(oxy.) does not offer a higher diagnostic power when compared with actual pH.