Toxicants that alter

Toxicants that alter circulating steroid hormone levels... 

Endocrine and Reproductive Effects. Because the male and female reproductive organs are under complex neuroendocrine and hormonal control, any toxicant that alters any of these processes can affect the reproductive system (see Chapters 17 and 20). In addition metals can act directly on the sex organs. Cadmium is known to produce testicular injury after acute exposure, and lead accumulation in the testes is associated with testicular degeneration, inhibition of spermatogenesis, and Leydig-cell atrophy. 

TOXICANTS THAT ALTER IMPULSE FORMATION OR CONDUCTION cause arrtiytiimias. 

TOXICANTS THAT ALTER CELL MEMBRANE FUNCTION... 

Toxicants that alter cell membrane control of ion movement affect the rale and force of carrKac contraction. 

In addition, naturally growing plants resist plant pathogen and Insect attack because resistance develops over time via natural selection (35). Also, most natural and crop plants have, as a part of their basic physical and chemical makeup, a wide array of mechanisms that help them resist pest attack. These Include chemical toxicants, repellents, altered plant nutrients, hairiness, thorns, and diverse combinations of these (35). 

Moving from single microorganisms to microbial communities, metals create selection pressure for microbes with cell structures that are less sensitive to metals. For example, mutations may occur that alter metal-binding sites of proteins without rendering the enzyme inactive. Another method for preventing metal toxicity is to produce excess amounts of the target so that there is an insufficient amount of metal to bind to all of the cellular molecules.4 35 53... 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

An example that alterations in the ubiquitin-proteasome system may be a primary event in AD, after ABP-induced toxicity or accumulation, was provided by Konishi et al. (273), who found that frameshift ubiquitin-B was present in subjects with AD pathology prior to development of dementia, probably accumulating in the initial steps of AD pathogenesis, whereas complement proteins were detected in AD patients but not in subjects with AD pathology and no symptoms of dementia, indicating the involvement of complement proteins in the later stage of dementia (273). 

It is in this context, that in 2009, the DART committee formed a Steering Team to work on a project titled Consensus List of Developmental Toxicants. The Steering Team published a report of their deliberations and defined developmental toxicant in terms of its concentration in vitro (27). Daston et al. (27) based the definitions of positive and negative developmental toxicants according to their exposure conditions. That is, compounds on the list could have an exposure concentration that is unequivocally positive and a concentration that is unequivocally negative. In addition, only permanent effects that alter fetal organization, particularly structural malformations, were considered developmental toxicity. For example, fetal weight decreases (which are commonly used endpoints in risk assessment) are not considered developmental toxicity for the purposes of this list. 

Therapeutic and toxic effects of drugs result from their interactions with molecules in the patient. Most drugs act by associating with specific macromolecules in ways that alter the macromolecules biochemical or biophysical activities. This idea, more than a century old, is embodied in the term receptor the component of a cell or organism that interacts with a drug and initiates the chain of events leading to the drug s observed effects. 

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