Workshop Report: Juvenile Toxicity Testing Protocols for Chemicals
There is increased awareness of the specific position of children when it comes to hazards of xenobiotic exposures. Children are not small adults, since their exposure patterns, compound kinetics and metabolism, and sensitivity of their developing organs may differ extensively from adults. Therefore, specific hazard and risk assessment for children is warranted. Current international hazard assessment test guidelines do not specifically address juvenile exposures and effects. In chemical risk assessment, exposure during the juvenile period (generally defined as from birth through puberty) is contained in the one- and two-generation reproduction toxicity study protocols (OECD TG 415 and 416) in which exposure commences in parental animals before mating and is continued in the offspring until the age of weaning or (for those animals selected as parents of the second generation in TG 416) into young adulthood (OECD, 1983, 2001). The novel extended one-generation reproductive toxicity study (EOGRTS, OECD TG 443) covers a much longer period for offspring exposure during juvenile life stages only, and in that aspect is more similar to a typical two-generation study (OECD, 2011). The developmental neurotoxicity test (OECD TG 426) applies exposure from gestation day 6 to postnatal day 21, thus exposing juvenile test subjects from birth until weaning (OECD, 2007). In the pharmaceutical arena, specific juvenile toxicity testing is an area of increasing concern in view of drug prescription issues for children. The Fifth Annual J&J Juvenile Toxicity Symposium on the subject was held in Gent, Belgium, 7 and 8 September 2011, in conjunction with the 39th Annual Meeting of the European Teratology Society (4-7 September 2011). On 8 September 2011, a satellite meeting was organized to specifically address juvenile toxicity testing issues for chemicals. The workshop focused on developmental neurotoxicity and developmental immune toxicity testing in juvenile animals. These subjects were addressed in great detail already when designing the OECD TG 433 EOGRTS on the basis of a published protocol (Cooper et al., 2006), and cohorts for these end points have been included. This signifies the importance conferred nowadays on these parameters. They parallel increasing prevalences of neurodevelopmental and immune related early onset diseases in the human population. Although the possible role in these diseases of chemical exposures is as yet far from clear, this situation warrants specific attention for related parameters in chemical hazard assessment. Two specific lectures covered each of these two classes of end points and are summarized below. Besides relevant end points, the exposure protocol is another important issue of study in juvenile toxicity testing. Using animal models for estimating human hazard and risk necessitates interspecies extrapolation, and dependent on definitions there are various options for choosing the juvenile exposure period in animal studies. A current project at RIVM, the Netherlands, addresses this issue for developmental immunotoxicity testing, and this subject was covered in another lecture.