External dose

Ferguson and Bowman 1990 Gilbert and Rice 1987 Hopper et al. 1986 Krasovskii et al. 1979 Levin et al. 1988 Massaro and Massaro 1987 Overmann 1977 Rice 1985a). It appears that animals are affected at roughly the same blood lead levels as humans. Measured neurotoxic effects in animals include significantly delayed motor function and reflexes, decreased performance on learning tasks, and impaired spatial discrimination. Additional animal studies are needed to investigate the neurotoxic effects of subchronic inhalation exposures to establish external dose-effect relationships. 

External dose Portion of dose equivalent received from radiation sources outside... 

Increased MW decreases >400 Da vapor pressure and decreases chance of delivery of external dose to respiratory tract... 

Operational relationships between internal dose, external dose, and... 

External dose, as used in the report, refers to the amount of chemical that is inhaled, is ingested, or comes in dermal contact and is available for systemic absorption. External dose is typically expressed in units of milligrams of chemical per kilogram of body weight per day (mg/kg/day). 

FIGURE 3-1 Operational relationships between internal dose, external dose, and biologic effects. Internal dose is measured through biomonitoring. Source Adapted from Bernard and Lauwerys 1986. 

Known relationship of external dose to response in animals O ... 

Group IV biomarkers also can be sampled and analyzed with reliable methods. In addition, the relationship between external dose and biomarker... 

The risk interpretation of biomonitoring results will tend to have additional uncertainties. That is because, in addition to the standard uncertainties encountered in risk assessment, there is the uncertainty of extrapolating from a blood or urinary concentration to an external dose. There will be variability both in the timing between sample draw and most recent exposure and in the relationship between blood concentration and dose. Those kinds of variability are compounded by uncertainty in the ability of a PK calculation or model to convert biomarker to dose accurately. For example, reliance on urinary biomarker results expressed per gram of urinary creatinine leads to an uncertain calculation of total chemical excretion per day because of the considerable variability in creatinine clearance per day. That complicates an otherwise simple approach to estimating dose. Furthermore, the conversion requires knowledge of fractional excretion via various pathways, which may not be present for a large sample of humans. The uncertainties created by these factors can be bounded via sensitivity and Monte... 

Glyphosate Urinary glyphosate Exposure pathways risk assessment external dose to toxic effect in animals limited analysis of biomarker to external dose Biomarker results can be put into risk context by using existing risk assessment... 

PFOA Serum PFOA External dose to toxic effect in animals biomarker to animal external dose therefore, biomarker to toxic effect in animals Biomarker results can estimate human risk need to extrapolate biomarker-response relationship across species... 

Lead Blood lead Biomarker to toxic effect in humans biomarker to external dose in humans Biomarker results can be used directly for estimation of human risk exposure apportionment and intervention possible... 

Dioxin Dioxin in blood or lipid Biomarker to body burden and external dose in humans body burden and external dose to toxicity in animals Biomarker results can estimate human risk exposure intervention possible... 

Styrene Urinary metabolites Biomarker to external dose (air concentration) in workers external dose to toxicity in animals biomarker to toxicity in workers Biomarker results can estimate risk in workers but not directly applicable to general population. 

How uncertainties and variability in creatinine clearance can affect urinary biomarker results and their extrapolation to external dose. 

As discussed in Chapter 5, benchmarks based on relevant populations, health end points, and internal doses (or plausible external doses) can be beneficial to study subjects and other concerned publics in evaluating individual and group biomonitoring results. For example, benchmarks could help to dampen health concerns that might otherwise be unduly high because of default lay beliefs about links between chemical body burdens and health outcomes. Conversely, exceedances of such benchmarks can be a signal for more attention and perhaps exposure reduction and other protective actions. 

Toxicologic studies need to be expanded to incorporate collection of biomonitoring data in animals that can be related to humans. Much of the dose-response information used in risk assessments is derived from animal toxicologic studies, and these do not collect information on internal dose. Therefore, dose-response relationships can be expressed only in terms of external dose (such as milligrams per kilogram per day). However, to interpret biomonitoring data, the relationship between internal dose (biomarker concentration) and effect must be understood. 

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