Age and Development

The interindividual variability reflects differences in the extent of exposure, in toxicokinetics as well as in toxicodynamics. The variability due to factors which influence the extent of exposure (physiological differences in the intake, e.g., inhalation rates) can be considered by means of suitable parameters for the internal exposure (absorbed dose, area under the curve AUC, plasma concentration) if sufficient information is available. With respect to toxicokinetic factors, interindi-vidual differences in the metabolism of chemicals are generally considered as the most significant explanatory factor. Hardly any knowledge is available with respect to the factors that influence toxicodynamics. In the following, a brief overview of the factors playing a role for the toxicokinetic and toxicodynamic differences is presented. 

The concept that infants and children may be a sensitive subgroup relates to their relative immaturity compared to adults. Children, as well as the unborn child, have in some cases appeared to be uniquely vulnerable to toxic effects of chemicals because periods of rapid growth and development render them more susceptible to some specific toxic effects when compared to adults. In addition to such toxicodynamic factors, differences in toxicokinetics may contribute to an increased susceptibility during these periods. It should be noted, however, that during the developmental and maturational periods the susceptibility to exposure to xenobiotics in children may be higher, equal, or even lower than in adults. Except for a few specific substances, not very much is known about whether and why the response to a substance may differ between age groups. It should also be borne in mind that, in terms of risk assessment, children are not simply small adults, but rather a unique population (Nielsen et al. 2001). 

Generally, it appears that effects of xenobiotics on organs or endpoints may be similar in children and adults, e.g., liver necrosis observed in adults will also be observed in children. As regards toxicodynamics, age-dependent differences are primarily related to the specific and unique effects that substances may have on the development of the embryo, fetus, and child in that the physiological development of the nervous, immune, and endocrine/reproductive systems continues until adolescence (12 to 18 years). Furthermore, receptors and other molecular targets for various xenobiotics are continuously developing during the embryonic, fetal, and infant periods. This may cause age-dependent differences in the outcome of receptor-xenobiotic interactions and even result in opposite effects of xenobiotics in infants and adults. The available data are insufficient to evaluate 

Toxicological Risk Assessments of Chemicals A Practical Guide 

Children s exposure pattern differs from that of adults and children may be more heavily exposed than adults to certain chemicals in the environment as they, on a body weight basis, breathe more air, drink more water, and eat more food than adults additionally, their behavior patterns, such as play close to the ground and hand-to-mouth activities, can increase their exposure. The differences in exposure patterns between children and adults are often used as an argument for increased susceptibility of children to chemicals however, it should be recognized that such differences are not related to increased vulnerability to chemicals but are purely related to an increased internal exposure (Nielsen et al. 2001). 

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Rottkamp CA, Nunomura A, Hirai K, Sayre LM, Perry G and Smith MA (2000). Will antioxidants fulfill their expectations for the treatment of Alzheimer disease Mechanisms of Ageing and Development, 116, 169-179. 

Based on this concept of correlation between high replication rate/high persistent mutation risk, Pike et al. (1983) formulated the hypothesis of breast tissue age and developed a mathematical model to predict the effects of exposure to ovarian hormones. This model incorporates reproductive and endocrine items related to breast cancer and is able to predict the relative risk of individual situations with results that are very close to those observed in clinical trials. According to this hypothesis, both the years of exposure and the circulating serum levels of estrogens are associated to short-term breast cancer risk in postmenopausal women (Toniolo et al. 1995). 

The PolyP content and exopolyphosphatase activity in rat tissues changed in the course of ageing and development (Lorenz et al., 1997a). The PolyP level in rat brain increased sixfold... 

Swegert CV, Dave KR, Katyare SS (1999) Mechanisms of Ageing and Development 112 27... 

Hass B, Lewis S, Duffy P, etal. (1996) Dietary restriction in humans Report on the Little Rock conference on the value, feasibility and parameters of the proposed study. Mechanisms of Ageing and Development 91 79-94. 

Hahn von, H. P. Primary causes of ageing a brief review of some modern theories and concepts. Mechanisms of Ageing and Development 2, 245 (1973). 

Gorman M. Development and the rights of older people. In Randel J, German T, Ewing D, eds. The Ageing and Development Report Poverty, Independence and the World s Older People. London Earthscan Publications, 1993 3-21. 

E. Mariani, G. Ravaglia, A. Meneghetti, et ah Natural immunity and bone remodelling hormones in the elderly. Mechanisms of Ageing and Development 102, 279 (1998). 

Early significant NTE inhibition after OP administration along with protection from OPIDN by reversible or non-aging NTE inhibitors, provide substantial evidence for a relationship between NTE inhibition and OPIDN [3,26,30,37], The relationship between NTE inhibition/aging and development OPIDN has potential to be exploited as a biomarker [3,26,38], Inhibition of brain NTE within hours of exposure to a neuropathic OP compound predicts the potential for OPIDN to appear in susceptible animal models (e.g., adult hens) after a delay of 1 to 3 weeks. 

The effects of age and development on the distribution of ascorbic acid in animals is not striking. During pregnancy and during the rapid... 

Goyns, M. H. and Lavery, W. L. Telomerase and mammalian ageing a critical appraisal. Mechanisms of Ageing and Development 114 69-77 2000. 

Children will be less fearful and more co-operative if they are informed according to their age and development. This does not mean that children should be told everything on every occasion since too many facts can create a greater fear. The parents are a good guide as to the appropriate level at which to pitch the information, and their cooperation is vital. The information should be given in a manner that the child can understand. Picture books are particularly useful. There are children s books that use characters familiar to children and have a hospital visit as a subject. If possible, a home-made booklet illustrated with pictures of an individual department and its X-ray equipment can be very useful. Topical children s character may be incorporated into the story. 

Pelvic trauma in children can result in a wide variety of different fractures and soft tissue injuries these range from isolated, relatively henign avulsion injuries to very complex multiple pelvic fractures and joint dissociations. The type of injury will depend on the causative mechanism as well as the age and development of the child. Compared with adults, pelvic fractures are relatively uncommon in children (ScHLiCKWEi and Keck 2005) and indicate a significant high energy impact. 

Rohner,T.C, Staab, D., Stoeckli, M. (2005) MALDI mass spectrometric imaging of biological tissue sections. Mechanisms of Ageing and Development, 126,177-185. 

Cutler, R.G. Mattson, M.P. (2001). Sphingomyehn and ceramide as regulators of development and hfespan. Mechanism of Ageing and Development, 122, 895-908. 

Mouton, R.E. Venable, M.E. (2000). Ceramide induces expression of the senescence histochemical marker, beta-galactosidase, in hiunan fibroblasts. Mechanism of Ageing and Development, 113,... 

Spaulding, C.C., Walford, R.L. Effros, R.B. (1997). Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice. Mechanism of Ageing and Development, 93, 87-94. 

Automated assays to study longevity in C. elegans. 2005. Mechanisms of Aging and Development, 126, 139-145. 

Hipkiss, A.R. 2006. On the mechanisms of aging suppression by dietary restriction-is persistent glycolysis the problem" Mechanisms of Aging and Development... 

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