Dose-response relationships regulation

Rowell PP, Li M (1997) Dose-response relationship for nicotine-induced up-regulation of rat brain nicotinic receptors. J Neurochem 68 1982-1989... 

Hemminki, K., Paasivirta, J., Kurkirinne, T. Virkki, L. (1980) Alkylation products of DNA bases by simple epoxides. Chem.-biol. Interact., 30, 259-270 Hine, C.H., Kodama, J.K., Wellington, J.S., Dunlap, M.K. Anderson H.H. (1956) The toxicology of glycidol and some glycidyl ethers. Arch. ind. Health, 14, 250-264 Hooper, K., LaDou, J., Rosenbaum, J.S. Book, S.A. (1992) Regulation of priority carcinogens and reproductive or developmental toxicants. Am. J. ind. Med., 22, 793-808 Hussain, S. (1984) Dose-response relationships for mutations induced in E. coli by some model compounds. Hereditas, 101, 57-68... 

For any hazardous substance, estimates of the relationship of dose to response in humans are based on either animal or human data. For example, only about 20 of the approximately 300 chemical carcinogens regulated by EPA have dose-response relationships based on human data from epidemiologic studies the remainder are based on animal bioassays. In contrast, the dose-response relationships for radiation are based primarily on the results of human epidemiologic studies. 

The chemical paradigm for risk management also is used in regulating exposures to hazardous chemicals that cause deterministic effects and exhibit a threshold in the dose-response relationship. For these substances, RfDs, which are often used to define acceptable exposures, represent negligible doses, because RfDs usually are well below assumed thresholds for deterministic responses in humans and action to reduce doses below RfDs generally is not required. This interpretation is supported by cases where doses above an RfD are allowed when achieving RfD is not feasible. A particular example... 

It was concluded from these and other studies in hypophysectomized animals that ACTH had no effect on aldosterone release. The volume-sensitive renal mechanism appears to be mainly responsible for postoperative aldosterone changes (S4), but it would now appear that ACTH also plays a part in regulating aldosterone secretion (S4). Removal of the pituitary leads to an immediate fall in aldosterone levels in adrenal venous blood (H9). A linear dose response relationship exists between the infusion rate of ACTH and aldosterone secretion rates (H9). Volume receptors in the right atrium and in the vascular tree respond to minor reductions in blood volume and play an important part in stimulating the aldosterone response (Bl, FI). Patients with suppression of cortisol production due to prolonged administration of steroids continue to secrete aldosterone and are able to increase their output after stress indicating the presence of another trophic factor as well as ACTH (T3). 

The dose-response relationship is the basis by which regulatory bodies define under what limits humans can be exposed to potentially toxic chemicals and yet not suffer adverse effects. A number of different government bodies establish regulations to define safe exposure conditions. The acceptable daily intake (ADI) is... 

Sulfate—The USEPA has 30 months to complete a joint study with the Centers for Disease Control and Prevention (CDC) to establish a reliable dose-response relationship. Must consider sulfate for regulation within 5 years. If the USEPA decides to regulate sulfate, it must include public notice requirements and allow alternative supplies to be provided to at-risk populations. 

Besides some of the technical complexities noted above, air Pb at toxic levels for human exposures is at microlevel and submicrolevel amounts. A brief reading of the levels of air Pb permissible in emissions to the human environment makes this apparent. This analytical reality meant that quantitative analysis of air Pb for purposes of health risk characterization and evaluation of dose—response relationships was not feasible. Second, the fact that lead entered ambient air where people live by either mobile (largely vehicular emissions) or point sources (e.g., smelters, incinerators, other pyrogenic sources) meant legislation and associated rales and regulations had to be crafted with these sources in mind. 

Dose—Response Relationships in Humans for Drinking Water Pb Relevant to Regulation... 

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