Individual variations

In risk characterization, step four, the human exposure situation is compared to the toxicity data from animal studies, and often a safety -margin approach is utilized. The safety margin is based on a knowledge of uncertainties and individual variation in sensitivity of animals and humans to the effects of chemical compounds. Usually one assumes that humans are more sensitive than experimental animals to the effects of chemicals. For this reason, a safety margin is often used. This margin contains two factors, differences in biotransformation within a species (human), usually 10, and differences in the sensitivity between species (e.g., rat vs. human), usually also 10. The safety factor which takes into consideration interindividual differences within the human population predominately indicates differences in biotransformation, but sensitivity to effects of chemicals is also taken into consideration (e.g., safety faaor of 4 for biotransformation and 2.5 for sensitivity 4 x 2.5 = 10). For example, if the lowest dose that does not cause any toxicity to rodents, rats, or mice, i.e., the no-ob-servable-adverse-effect level (NOAEL) is 100 mg/kg, this dose is divided by the safety factor of 100. The safe dose level for humans would be then 1 mg/kg. Occasionally, a NOAEL is not found, and one has to use the lowest-observable-adverse-effect level (LOAEL) in safety assessment. In this situation, often an additional un-... 

Both NOEL and LOEL are based on a wide range of toxic substance effects, while NOAEL and LOAEL are based on only adverse effects. Neither set of parameters take into account the individual variation in susceptibility. 

Thus, to give an STO-3G fit to a Is orbital with exponent = 1 we have to take the three primitive Is GTOs with exponents cti =0.109818, aj — 0.405 771 and 03 = 2.227 66. Their individual variations with distance is shown in Figure 9.3. 

The mean valmber the dry weight, (3.95 0.20) X 0 10 gram, agrees with results obtained in microchemical analyses of samples containing many cells. Such analyses cannot, of course, reveal the individual variations that appear in Table 11-3. 

The complex nature of the mass transfer of carotenoids to absorbable lipid species, the diversity of raw and processed foods consumed, and individual variations in the degree of mastication, will lead to differences in the amount of carotenoid that becomes bioaccessible and potentially available for absorption. By understanding the underlying mechanisms of these processes, for a wider range of fruit and vegetable constituents, it will become possible... 

In general, carotenoids in foods are C40 tetraterpenoids comprised of eight C5 isoprenoid (ip) units (Figure 2.2.2) whose order is inverted at the molecule center, joined head to tail, except at the center where a tail-to-tail linkage reverses the order, resulting in a symmetrical molecule. This produces the parent C40 carbon skeleton from which all the individual variations are derived. ... 

The object of all coating procedures is the distribution of the stationary phase as a thin, even film that coaq>letely covers the glass surface [139,140,143,146]. Dynulc coating and static coating methods, with several individual variations are used for this purpose. 

CYP2C19 is another example of the existence of both cross-ethnic and inter-individual variations in drug metabolism. This enzyme is involved in the metabolism of many psychotropics such as diazepam and tertiary tricyclic antidepressants, as well as one of the selective serotonin re-uptake inhibitors (SSRIs), citalopram. Using S-mephenytoin as the probe, previous studies showed that up to 20% of East Asians (Chinese, Japanese, and Koreans) are PMs, when only 3-5%... 

As is apparent from the literature reviewed above, that culture and ethnicity are powerful determinants of an individual s response to psychopharmacotherapy. Progress in this regard will vastly improve our current practice in using medications. However, it is necessary to remember that there are often very substantial inter-individual variations within any defined cultural or ethnic group, and that ethnic variations in pharmacological responses should not be interpreted stereotypically. 

Ethnic differences have been shown to influence response to psychotropic medications. Much of the focus on the explanation for such differences has been on drug-metabolizing (CYP) enzymes of the liver and their sway over pharmacokinetic factors. It is now well recognized that differences in the distribution of polymorphic variants of CYP enzymes exist between different ethnic groups. However, within ethnic groups there are considerable inter-individual variations in drug kinetics, which may not be accounted for solely by genetic variation. Responses to pharmacotherapy are multifaceted and involve the interaction of environmental and... 

YK Tam. Individual variation in first-pass metabolism. Clin Pharmacokin 25 300-332, 1993. 

Levels of ACHE and PCHE vary in healthy people because of genetic differences or under specific physio-pathological conditions inter-individual coefficients of variation of cholinesterase activity have been determined to be about 15 to 25% for PCHE and 10 to 18% for RBC-ACHE. Corresponding figures for intra-individual variations are 6% and 3 to 7%, respectively (Dillon and Ho, 1987). 

Some OP compounds induce delayed neurotoxic effects ("delayed neuropathy") after acute poisoning. This delayed neurotoxic action is independent of cholinesterase inhibition but related to phosphorylation of a specific esterasic enzyme in the nervous tissue, called "neurotoxic esterase" or "neuropathy target esterase" (NTE) (Johnson, 1982). NTE is present in the nervous tissue, liver lymphocytes, platelets, and other tissues, but its physiological function is unknown. There is a rather large inter-individual variation of lymphocyte and platelet NTE activity (Table 2). 

Bonithon-Kopp C, Huel G, Grasmick C, et al. 1986c. Effects of pregnancy on the inter-individual variations in blood lead levels of lead, cadmium and mercury. Biol Res Preg 7 37-42. 

Hammond Jr., B. R. et al. (1997). Individual variations in the spatial profile of human macular pigment. Journal of the Optical Society of America A 14 1-10. 

Russell, M.A. Subjective and behavioural effects of nicotine in humans some sources of individual variation. Prog. Brain Res. 79 289, 1989. 

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