Exposure relationships

Greene T, Emhart CB. 1991. Prenatal and preschool age lead exposure Relationship with size. Neurotoxicology and Teratology 13 417-427. 

Raghavan SRV, Culver BD, Gonick HC. 1990. Erythrocyte lead-binding protein after occupation exposure Relationship to lead toxicity. Environ Res 22 264-270. 

This exposure relationship is frequently more important in establishing human safety margins, as dose alone may be subject to a variety of differences between species such as absolute bioavailability, distribution, and excretion. This aspect, now commonly referred to as "toxicokinetics," has been outlined in an ICH guideline.6 This guideline specifies minimum requirements in terms of number of time points examined, number of animals per time point, and the requirements for calculation of various pharmacokinetic parameters such as Cmax, AUC. These will become important for comparison with human data as it becomes available later. 

Guilherme, S., M. Valega, M.E. Pereira, M.A. Santos, and M. Pacheco. 2008. Antioxidant and biotransformation responses in Liza aurata under environmental mercury exposure—relationship with mercury accumulation and implications for public health. Mar. Pollut. Bull. 56 845-859. 

For each of the exposure pathways, a relationship between soil concentration and exposure of the human receptor can be developed. Developing this relationship for each of the exposure possibilities allows the land use planner to assess how the choices for land use may influence the exposure relationships. Once the relationships between soil concentration and exposure are established, the relationships can be presented graphically, as shown in Figure 5.6. The relationships shown in this diagram are hypothetical and would ultimately depend on several chemical, physiological, and exposure factors. 

The pharmacokinetic evaluation of biopharmaceuticals is generally simplified by the usual metabolism of products to small peptides and to amino acids, and thus classical biotransformation and metabolism studies are rarely necessary. Routine studies to assess mass balance are not useful. However, both single- and multiple-dose toxicokinetic data are essential in safety pharmacology asessments, and these can be complicated by two factors (1) biphasic clearance with a saturable, initial, receptor-dependent clearance phase, which may cause nonlinearity in dose-exposure relationships and doseresponses [14] and (2) antibody production against an antigenic biopharmaceutical that can alter clearance or activity in more chronic repeat-dose safety studies in the preclinical model. 

Krishna et al. (2002). Occasionally, such a short term infusion is recommended instead of a bolus intravenous administration (Chiou 1989, p 283). The advantage is to avoid high blood concentrations shortly after intravenous administration which may be in conflict with the assumed linear dose-exposure relationship (validity of linear relation at border concentration ). The advantage of the intravenous bolus injection is the lower/shorter stress situation for the animals (and may be also for the experimenter) which might influence the reproducibility of the study results. 

Jones RN, McLoud T, Rockoff SD. 1988b. The radiographic pleural abnormalities in asbestos exposure Relationship to physiologic abnormalities. J Thoracic Imaging 3 57-66. 

Human PK is determined for the first time in Phase I, initially as a series of single doses escalated through several dose levels to establish the dose-exposure relationship and also the half-life. Because an oral dose may have an extended period of absorption, it is not possible to get the true clearance or volume of distribution from an oral dose a confounding with bioavailability may occur. Furthermore, sometimes absorption is slower... 

Hitchcock SA, Pennington LD (2006) Structure-brain exposure relationships. J Med Chem 49(26) 7559-7583... 

McCahon, C.P., S.F. Barton, and D. Pascoe. 1990. The toxicity of phenol to the freshwater crustacean Aselus aquaticus (L.) during periodic exposure—relationship between sub-lethal responses and body phenol concentrations. Arch. Environ. Contam. Toxicol. 19 926-929. 

This simple statement has profound implications in the management of risk, i.e., that even toxic substances can be effectively managed through control of exposure, at least in industrial environments, and even substances typically thought to be safe can become toxic if exposure is excessive. Although the hazard-exposure relationship suggests that risk is eliminated if exposure is zero, in practice achievement of zero risk is not possible. Under the Toxic Substances Control Act (TSCA), the Environmental Protection Agency (EPA) carries out three risk assessments one each for acute and chronic... 

Fig. 3. (a) Growth inhibitory potencies against aerobic UV4 cells after a 1-hr exposure relationship to substituent electronic parameter, (b) CT q values determined by clonogenic assay relationship to substituent electronic parameter. 

A. Specific levels. The whole-blood lead level is the most useful indicator of lead exposure. Relationships between blood lead levels and clinical findings have generally been based on subacute or chronic exposure and not on transiently high values that may result immediately after acute exposure. In addition, there may be considerable interindividual variability. Note Blood lead samples must be drawn and stored In lead-free syringes and tubes ( trace metals tube or royal blue stopper tube containing heparin or EDTA). 

Structure-brain exposure relationships. Journal of Medicinal Chemistry, 49, 7559. 

Recognizing asbestos. Adverse health effects associated with exposure. Relationship between smoking and asbestos in causing iung cancer. 

More refined forms of regression analyses have emerged to better quantify source—exposure and source—pathway—exposure relationships for lead. A particularly useful form is a variation on the multiple regression technique of structural equation modeling (SEM). Figme 9.1 shows interior dust, the principal Pb exposure pathway for infants and toddlers, arising from exterior Pb dusts, interior Pb paint, or secondary occupational ( take-home ) dusts. 

RECENT STUDIES OF ANEMIA IN HUMAN POPULATIONS VIA THE HB-Pb EXPOSURE RELATIONSHIP... 

Children in this pooled analysis were in the infancy age band and had an average age of 16 months. Consequently, their Pb exposures were largely those characterizable as one or more interior home environments with limited external, i.e., public, contact with Pb in settings such as daycare centers. In these exposure cases, interior dust Pb and bulk surficial soil (plus external surface dust Pb) are known to be principal sources and pathways for infant—toddler residential Pb exposures. Dust Pb exposures with lead loadings as the metric rather than Pb concentration appear to better capture the statistical size of any exposure relationships (Lanphear et al., 1995 Milar and Mushak, 1982). 

Gilbertson, M.W., Paulus, L.A., Williston, S.K., et al, 2006. Neurocognitive function in monozygotic twins discordant for combat exposure relationship to posttraumatic stress disorder. J. Abnorm. Psychol. 115, 484-495. 

---