Postnatal testing

Gray LE Jr, Kavlock RJ, Ostby J, et al. 1983. Assessment of the utility of postnatal testing following prenatal exposure to forty chemicals. Prog Clin Biol Res 140 39-62. 

If peri-postnatal tests, developmental neurotoxicity smdies, or specific male or female fertility studies are available they can be used to identify a substance as being toxic to reproduction. Data from such studies alone cannot be used to identify a substance as being of no concern in relation to reproduction. 

The developmental changes seen in the immediate postnatal period in altricial rodents and especially in the early stages of marsupials, are an expected outcome of their shortened gestational period, early parturition and consequential dependent status. Regrettably, the relative contribution of the main and accessory chemosensory route(s) cannot be fully assessed. The lesser importance of the AOS (by some tests)... 

Impairment has also been reported at low blood lead levels in other types of behavior/leaming studies in rats. In a test of spatial discrimination, rats were exposed to lead acetate at 745 mg lead/kg/day in the diet indirectly via administration to their dams through gestation and lactation and then directly until testing (at 100 and 200 days of age) (Winneke et al. 1977). The lead-exposed rats were slower to leam the discrimination than were controls. Their PbB levels at postnatal day 16 averaged 26.6 pg/dL and the levels at 190 days averaged 28.5 pg/dL. 

A review of the literature on chemical-induced immunosuppression in rats and mice, exposed during the pre- and/or postnatal period, was compared to exposure of adults. Five known immunosuppressants (i.e., TCDD, TBTO, DES, Pb, and diazepam) were reviewed. The data revealed that the developing immune system was more sensitive to chemical exposure than the mature immune system. Based on these evaluations, the authors concluded that it was reasonable to assume that testing only in adults would not provide a sufficient level of sensitivity to define immunotoxicity in the neonate 132. In summary, this chapter provides compelling evidence that the developing, compared to the mature, immune system is more vulnerable to perturbation. 

To confirm their results and check for methodological problems, some studies have been carried out. As there was a probability that hypothermic conditions during temporary removal from dam may have affected the results, Pauluhn and Schmuck administered S-bioallethrin and deltamethrin to neonatal mice from postnatal day 10 to 16 under a hypo-, normo-, or hyperthermic environment, and measured the MAChR density at the age of 17 days [51]. Increase in MAChR in Cortex at PND 17 in animals treated with S-bioallethrin was observed. Meanwhile, no changes were observed in animals treated with deltamethrin. In addition, an enormous influence of environmental temperature on the density of MAChR receptors in the crude synaptosomal fraction of the cerebral cortex was ascertained. Tsuji et al. exposed mouse dams with their litters to D-allethrin by inhalation for 6 h from postnatal day 10 to 16. The inhalation administration method is the most relevant route of exposure for humans, including babies and infants, after indoor use of D-allethrin. The neonatal exposure to D-allethrin by inhalation did not induce effects either on the brain MAChR density or motor activity at 17 days and 4 months of age, or on performance in the leaming/memory test at 11 months of age [52]. Other unpublished studies with D-allethrin, S -bioallethrin, or deltamethrin were examined to confirm the results of Eriksson et al. and showed inconsistent results [53]. The reasons for discrepancy among these findings are unknown. 

To summarize, the current status of assessment of toxicity in postnatal mammals, in response to the pediatric initiatives covered in FDAMA, is an extremely fluid situation. One needs to carefully consider a variety of factors in designing the study and should discuss proposed testing programs with the appropriate office at ODER. 

---