Variability of response

Individuals differ in their sensitivity to odor. Figure 14-7 shows a typical distribution of sensitivities to ethylsulfide vapor (17). There are currently no guidelines on inclusion or exclusion of individuals with abnormally high or low sensitivity. This variability of response complicates the data treatment procedure. In many instances, the goal is to determine some mean value for the threshold representative of the panel as a whole. The small size of panels (generally fewer than 10 people) and the distribution of individual sensitivities require sophisticated statistical procedures to find the threshold from the responses. 

Further studies have shown additional cancer types, most notably ovarian and bladder cancer, non-Hodgkin s lymphoma and acute myeloid leukaemia, to be at least partially responsive to IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on various cancer types is variability of response. Several trials have yielded conflicting results, and no reliable predictor of clinical response is available. 

Fiuid and eiectroiyte baiance The use of this drug does not preclude the administration of appropriate fluid and electrolyte therapy. Dehydration, particularly in children, may further influence the variability of response and may predispose to delayed difenoxin intoxication. Drug-induced inhibition of peristalsis may result in fluid retention in the colon, and this may further aggravate dehydration and electrolyte imbalance. 

Children younger than 2 years of age because of greater variability of response hypersensitivity to diphenoxylate or atropine obstructive jaundice diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria. 

Children Not recommended for use in children younger than 2 years of age. Use special caution in young children because of the greater variability of response in this age group. Dehydration may further influence variability of response. Dosage has not been established for children in treatment of chronic diarrhea. 

These jumping spiders are known for their excellent vision, but there is evidence from several species that they also use pheromones for communication, as suggested by Crane (1949). More than 30 species now have been investigated, making this the most thoroughly studied family. The earlier work has been reviewed and will not be discussed in detail here (see Table 4.1 for list of species Pollard et al., 1987 Jackson, 1987). In addition, the variability of response to pheromones by individual males has been addressed (Jackson and Cooper, 1990). 

More significant, however, was an additional observation pertaining to variability of response. It is common knowledge that under physiological conditions and particularly in awake... 

Perhaps also related to these observations on variability of response and its reaction to LSD-25 are the findings of Witt (1951). This author, in his extended studies on the webbuilding ability of spiders, found that LSD-25 in low doses... 

Fluoxetine is a selective serotonin-reuptake inhibitor (SSRI) that produces a net increase in (post-synaptic motor neuron) serotonin delivery after 4-6 weeks of use. A double-blind, randomized cross-over trial compared fluoxetine to the tricyclic antidepressant agent protriptyline and placebo in 12 patients with sleep-disordered breathing [52], The group apnea-hypopnea index (AHI) improved with fluoxetine compared to placebo, but there was great variability of response and other measures of disordered sleep did not change. These potentially beneficial results in a small number of patients need to be replicated in well-designed larger studies to support a useful role in clinical practice. 

The rationale supporting use of EDi0 as the benchmark dose is that a 10 percent response is at or just below the limit of sensitivity in most animal studies. Use of the lower confidence limit of the benchmark dose, rather than the best (maximum likelihood) estimate (EDio), as the point of departure accounts for experimental uncertainty the difference between the lower confidence limit and the best estimate does not provide information on the variability of responses in humans. In risk assessments for substances that induce deterministic effects, a dose at which significant effects are not observed is not necessarily a dose that results in no effects in any animals, due to the limited sample size. NOAEL obtained using most study protocols is about the same as an LED10. 

Schafer Al. Genetic and acquired determinants of individual variability of response to antiplatelet drugs. Circulation 2003 108 910-91 I. 

Discussion of the inadequacy of the data that are the basis for a UF of 10. For example, the analysis may depend upon data collected in only one species, high variability of response, or uncertainties in exposure measurement. The statement may point to data gaps that could be filled where the need exists. 

The NAC/AEGL Committee estimates the range in variability of response to specific chemical exposures primarily on the basis of quantitative human data. Acceptable experimental data are more likely to be available for AEGL-1 and AEGL-2 endpoints than for AEGL-3 endpoints. For example, numerous studies have considered induction of bronchospasm after controlled exposmes to sulfur dioxide (SO2) in asthmatic and nonasthmatic individuals (see references below). There is marked individual variability in the severity of reaction to inhalation of low concentrations of SO2. Asthmatics, individuals with hyper-reactive airways, smokers, and those with chronic respiratory or cardiac disease respond at relatively lower concentrations (Aleksieva 1983 Simon 1986). Susceptibility may also be increased in people over 60 years of age, but reports have not been consistent (Rondinelli et al. 1987 Koenig et al. 1993). By contrast, comparable human data for AEGL-3 tier concentrations are limited to anecdotal case reports. 

Irritant (Category 2) (applies to all authorities) (1) Mean value of > 2.3 < 4.0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions or (2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling or (3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above. 

Furst DE. The basis for variability of response to antirheumatic drugs. Bailliere s Clin Rheumatol 1988 2(2) 395 24. 

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