Age-Related Susceptibility

A human study of methemoglobinemia among children and nursing infants exposed to higher concentrations of chlorine dioxide and chlorite in the drinking water might provide valuable information regarding age-related susceptibility. 

The 1996 Food Quality Protection Act (FQPA) now requires that an additional safety factor of 10 be used in the risk assessment of pesticides to ensure the safety of infants and children, unless the EPA can show that an adequate margin of safety is assured with out it (Scheuplein, 2000). The rational behind this additional safety factor is that infants and children have different dietary consumption patterns than adults and infants, and children are more susceptible to toxicants than adults. We do know from pharmacokinetics studies with various human pharmaceuticals that drug elimination is slower in infants up to 6 months of age than in adults, and therefore the potential exists for greater tissue concentrations and vulnerability for neonatal and postnatal effects. Based on these observations, the US EPA supports a default safety factor greater or less than 10, which may be used on the basis of reliable data. However, there are few scientific data from humans or animals that permit comparisons of sensitivities of children and adults, but there are some examples, such as lead, where children are the more sensitive population. It some cases qualitative differences in age-related susceptibility are small beyond 6 months of age, and quantitative differences in toxicity between children and adults can sometimes be less than a factor of 2 or 3. 

Auer, R.N. 1991. Excitotoxic mechanisms, and age-related susceptibility to brain damage in ischemia, hypoglycemia and toxic mussel poisoning. Neurotoxicology 12, 541-546. 

Tainter 1938) and rabbits exposed to 0.25% 2,4-DNP in the diet for 8 hours (total dose 41 mg/kg) (Bettman 1946) did not develop cataracts. However, as discussed in Section 2.4 (Ocular Effects), cataracts were induced in rabbits injected intraperitoneally with 2,4-DNP (Gehring and Buerge 1969a). Immature rabbits (10 days old) were more susceptible than 62-day- old rabbits, while no cataracts were induced in 90-day-old rabbits. This age-related susceptibility to the cataract formation was attributed to a decreased ability to metabolize substances and an increased permeability of the blood-ocular fluid barrier in the very young rabbits. 

Bums-Guydish, S. M., Olomu, I. N., Zhao, H., Wong, R. J., Stevenson, D. K., and Contag, C. H. (2005) Monitoring age-related susceptibility of young mice to oral Salmonella enterica serovar Typhimurium infection using an in vivo murine model. Pediatr. Res. 58, 153-158. 

Present information indicates a potential for age-related differences in susceptibility to methyl parathion. However, data are limited in both human and animal studies. 

Limited information regarding potential for age-related differences in susceptibility to methyl parathion in humans was reported by Dean et al. (1984). Seven children (ranging in age from 2 to 11 years) and three adults were exposed to unknown concentrations of methyl parathion sprayed illegally inside a house at a concentration of 4% (>3 times the recommended concentration for field applications). The children... 

The only other information regarding the potential for age-related differences in susceptibility to methyl parathion came from a study by Garcia-Lopez and Monteoliva (1988). The investigators showed increasing mean erythrocyte acetylcholinesterase activity levels with increasing age range, starting at birth (in 10-year increments and >60 years of age) in both males and females. However, it is not known whether increased erythrocyte acetylcholinesterase activity indicates a decreased susceptibility to methyl parathion toxicity. 

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). 

Swaroop, A, Branham, KEH, Chen, W, and Abecasis, G, 2007. Genetic susceptibility to age-related macular degeneration A paradigm for dissecting complex disease traits. Hum Mol Genet 16, R174—R182. 

Age-related reductions in bone marrow reserve can render the elderly patient more susceptible to anemia that is caused by multiple minor and often unrecognized diseases (e.g., nutritional deficiencies) that negatively affect erythropoiesis. 

ILSI, International Life Sciences Institute, Research Needs on Age-related Differences in Susceptibility to Chemical Toxicants. Report of an ILSI Risk Science Institute Working Group. Washington, DC ILSI Risk Science Institute, 1996. 

ILSI RSI workshop Research needs on age-related differences in susceptibility to chemical toxicants. Washington, DC June, 1996... 

In Tables 10 and 11, meta-analyses based on 576 cases gleaned by Goodman from a number of reports, there are only moderate variations in mortality among cases grouped by route of administration or by age. Using chi-square analysis, Goodman found no statistically significant age-related differences in susceptibility to the lethal effects of atropine. 

Refer to Section 3.7 for information regarding age-related differences in susceptibility to chlorine dioxide and chlorite. 

Children s Susceptibility. Neurodevelopmental delays and postnatal changes in serum thyroid hormone levels have been observed in animals following exposure of their mothers to chlorine dioxide or chlorite during gestation and/or lactation (Carlton and Smith 1985 Carlton et al. 1987 Gill et al. 2000 Mobley et al. 1990 Orme et al. 1985 Taylor and Pfohl 1985 Toth et al. 1990). It is not known whether age-related differences in toxicokinetic parameters exist for chlorine dioxide or chlorite. Additional studies should be designed to further examine neurodevelopmental toxicity and underlying mechanisms. 

Several age-related changes contribute to the high incidence of infections in geriatric patients. There appears to be a reduction in host defenses in the elderly, manifested in the increase in both serious infections and cancer. This may reflect an alteration in T-lymphocyte function. In the lungs, a major age and tobacco-dependent decrease in mucociliary clearance significantly increases susceptibility to infection. In the urinary tract, the incidence of serious infection is greatly increased by urinary retention and catheterization in men. 

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