Body size, toxic effects

In practice, this means that no adjustment for difference in body size is needed for a NOAEC obtained for systemic effects in an inhalation toxicity study (van Genderen 1988, Feron et al. 1990, Vermeire et al. 1999, KEMI 2003). For example, a NOAEC of 50 mg/m observed for laboratory animals is also the equivalent human NOAEC (note that so far species-specific sensitivity has not been taken into account). 

Gronlund (1992) has investigated methods used for quantitative risk assessment of non-genotoxic substances, with special regard to the selection of assessment factors. Gronlund found that humans, in most cases, seem to be more sensitive to the toxic effects of chemicals than experimental animals, and that the traditional 10-fold factor for interspecies differences apparently is too small in order to cover the real variation. It was also noted that a general interspecies factor to cover all types of chemicals and all types of experimental animals cannot be expected. It was concluded that a 10-fold factor for interspecies variability probably protects a majority, but not all of the population, provided that the dose correction for differences in body size between experimental animals and humans is performed by the body surface area approach (Section 5.3.2.2). If the dose correction is based on the body weight approach (Section 5.3.2.1), the 10-fold factor was considered to be too small in most cases. 

Larger particles (several micrometers in size) are deposited in the ciliated portion and are cleared from the respiratory system by muco-ciliary action into the gastronomical tract, but may produce systemic toxic effects by absorption in body fluids. Finer particles reach the lower non-ciliated portion of the lungs, are cleared very slowly, and are responsible for diseases such as pneumoconiosis and lung cancer. Metallic lead (Pb), tellurium ( ), selenium (Se), and platinum (Pt) are known to cause both systemic and respiratory toxicity in laboratory animals and several cases of acute and chronic poisoning among metal workers have also been documented. 

Cyclosporine is a macrolide antibiotic and has been used as an immunosuppressive agent. Cyclosporine can cause both renal and nonrenal toxicity. Clinically renal toxicity consists of four discrete syndromes which include acute reversible renal functional impairment, delayed renal allograft function, acute vasculopathy, and chronic nephropathy with interstitial fibrosis. Proximal tubular epithelium is uniquely sensitive to the toxic effect. The toxic effect is characterized by isometric cytoplasmic vacuolations (several small equally sized vacuoles in cytoplasm), necrosis with or without subsequent mineralization, inclusion bodies (giant mitochondria), and giant lysosomes. Acute vasculopathy consists of vacuolization of the arteriolar smooth muscles and endothelial cells leading to necrosis. In some cases, thrombotic microangiopathy develops, characterized by thrombosis of the renal micro vasculature. Long-term treatment with cyclosporine results in chronic nephropathy with interstitial fibrosis (Chamey et al., 2004). 

Because of digoxin s narrow therapeutic range, toxicity can often occur, especially in those who have predisposing factors, such as hypokalemia, concurrent therapy with potassium wasting diuretics, age (elderly and pediatrics), small body size, and drug interactions. Common signs of toxicity include Gl complaints (nausea, vomiting, and anorexia), arrhythmias, and CNS effects (i.e., confusion, hallucinations, and visual disturbances). 

Toxic to aquatic organisms for example, there was an inhibiting effect of 20-40 ppm aniline on the pigmentation of Xenopus laevis embryos, and of a concentration as low as 1 ppm on the body size of the young toads. Investigation of the death of pine trees in the United States found air pollution from aniline as the most likely causal agent for the needle necrosis and needle abscission. 

On the other hand, community structure may change through indirect mechanisms. Indirect effects are those that are not due to toxic effects per se. For example, an insecticide may not be toxic to birds, but the birds may disappear because the insecticide kills off the insects on which it feeds. Conversely, the body size and population density of a species of minnow may increase in contaminated sites due to toxic effects on competing species (more food available for the minnow) or on predators such as bass. It has also been suggested that such changes in community structure come about because some species are more genetically plastic than others, and so are better able to adapt to novel stressors such as pollution. Thus, the more sensitive species would not be able to adapt to this stressor and become extinct locally. These types of perturbations in community structure and dynamics may ultimately compromise the stability, sustainability, and productivity of affected ecosystems. 

Children are most vulnerable to the effects of toxic chemical exposure. Because they are still developing, children are affected in adverse ways that adults are not (Chapters 24 and 33). For their body sizes, children inhale more air, drink more water, and eat more food than adults and are thereby exposed to correspondingly higher levels of toxic environmental chemicals. This dictates that children require greater protection from exposures to toxic chemicals and their mixtures than adults do. 

M.V. Moore, C.L. Folt (1993). Zooplankton body size and community structure effects of thermal and toxicant stress. Trends Ecol. Evol, 8,178-183. 

Chelation Children are particularly susceptible to lead poisoning, due to their smaller body sizes and rapid rates of development. In serious cases, a process called chelation therapy might be the only way to save the child s life. Chelation therapy reverses one important effect of lead poisioning, replacing toxic lead with beneficial calcium in the body. 

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