Neonate sensitivity

The experimental counterpart to the human epidemiologic data from Iraq and Minamata provides cogent parallels. The fetal and neonatal sensitivity observed in humans has been confirmed in various species rmd, in fact, has also been documented once the organisms mature. The earliest experimental data indicating such permanence came from Spyker. She treated pregnant mice with methylmercury at a dose of 8 mg kg. After birth, the offspring were cross-fostered, then followed for their lifetimes. Animcds with obvi-... 

Pope et al. (1991) found that 7-day-old Sprague-Dawley rat pups were approximately twice as sensitive as 80-100-day-old adults to single subcutaneous doses of methyl parathion the highest nonlethal dose 7.8 mg/kg for the neonates and 18.0 mg/kg for adults. Initially, both neonates and adults exhibited similarly reduced brain acetylcholinesterase activity levels (approximately 10% that of controls) ... 

An additional study reported age-dependent effects. Lakshmana and Raju (1994) found that oral treatment of rat pups with endosulfan from postnatal days 2-10 resulted in changes in the concentration of noradrenalin, dopamine, and serotonin in various brain areas that differed either in magnitude or direction from changes seen in pups treated from postnatal days 2-23. While the results from this study do not necessarily indicate that neonates are more sensitive to the toxic effects of endosulfan, they do show that the duration of exposure in neonates is an important parameter to consider. 

For all 12 mother-infant pairs, either the mother or the infant s toxicology report was subsequently positive for PCP. In nine cases, the screens for both mother and infant were positive. In two cases, the mother s results were positive and the infant s were negative. In one case, the infant had a positive result while the mother s test was negative. Test sensitivity, specimen handling procedures, and delays in obtaining specimens undoubtedly contributed to the inconsistency in paired results. Cocaine, codeine, and glutethemide, in addition to phencyclidine, were identified in the urine toxicology screens of two mothers and their neonates. 

Children s Susceptibility. No studies were located in which comparisons were made between the sensitivity of children and adults to the toxicity of americium. Animal studies indicate that juvenile dogs are less susceptible than adults to americium-induced bone cancer (Lloyd et al. 1999). No direct evidence was located to indicate that the pharmacokinetics of americium in children may be different from that in adults. Based on dosimetric considerations related to differences in the parameters of available models, as well as studies in animals, it seems likely that children may be more susceptible to americium toxicity than are adults by virtue of age-related differences in pharmacokinetics. Absorption of ingested americium may be as much as 200 times greater in neonatal animals than in adults. (Bomford and Harrison 1986 David and Harrison 1984 Sullivan et al. 1985). 

Differences in receptor sensitivity have been offered to explain the spectrum of unexpected drug responses observed in children. Neonates and young children are at increased risk to experience paradoxical CNS stimulation following antihistamine administration. Symptoms observed in pediatric cases of acute overdose include hallucinations, excitation, and seizures. A physiological explanation for this reaction has not been identified. Antihistamines should not be included in over-the-counter (OTC) cough and cold products recommended for infants and young children. 

Developmentally, thyroid hormones interact with sex hormones such that hypothyroidism prolongs the critical period for testosterone-induced defeminization (see below) [3] in contrast, the hyperthyroid state prematurely terminates the sensitivity to testosterone [3]. Undoubtedly, an important link in these and other effects is synapse formation. Hypothyroidism increases synaptic density, at least transiently [3]. Interesting parallels with synapse formation are reported for learning behavior in rats neonatal hypothyroidism impairs learning ability, whereas hyperthyroidism accelerates learning initially, followed by a decline later in life [3]. 

Neonates and infants may metabolize drugs more slowly, and children may metabolize drugs more rapidly than adults. Lower doses of AEDs are often required in the elderly. Some elderly patients have increased receptor sensitivity to CNS drugs, making the accepted therapeutic range invalid. 

Sensitivity of the immune system to Pb appears to differ across life stages, and studies in rodents suggest that the gestational and neonatal periods are the most sensitive. Compared to adults, the increased dose sensitivity of the embryo-fetus would appear to fall in the range of 3-12X depending upon the immune endpoint considered. Recent studies have suggested that exposure of embryos to Pb producing neonatal BLLs below 10 pg/dL can also produce later-life immunotoxicity (Table 12.2). Furthermore,... 

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. 

Fitzgerald (1954) injected newborn mice (less than 12 h old) and adult mice subcutaneously with sodium cyanide (NaCN). The threshold for lethality was the same in newborn and adult male and female male mice, NaCN at 2 mg/kg. The dose-response curve for neonatal mice was much steeper than for adult mice, which resulted in a lower LC50 value. The LC50 for adult male mice was approximately 5 mg/kg for female mice it was 3.5 to 3.7 mg/kg and for neonatal mice it was between 2.0 and 2.5 mg/kg. On the basis of the threshold for lethality, newborn and adult mice were equally sensitive to HCN, but on the basis of LC50 values, newborn mice were approximately two to three times more sensitive than adult male mice. 

B.M. Sutherland used in vitro experiments with human neonatal foreskin fibroblasts in buffer solution to show that DNA-pyrimidine dimer formation under a sunlamp was sensitized by p-aminobenzoic acid. Cells illuminated in the presence of the acid had a 10-fold higher frequency of transformation to anchorage-independant growth than cells irradiated in buffer alone [41]. 

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