Relationship of exposure

The database for HFC-134a is extensive it contains studies with both human subjects and animal models. Potentially sensitive populations, including patients with COPD and adult and pediatric asthmatic patients, were tested with direct inhalation of HFC-134a from metered-dose inhalers. The response of these groups was no different than that of healthy adults. The animal studies covered acute, subchronic, and chronic exposure durations and addressed systemic toxicity as well as neurotoxicity, reproductive and developmental effects, cardiac sensitization, genotoxicity, and carcinogenicity. The metabolism of HFC-134a is well understood, and the relationship of exposure con... 

This chapter summarizes the known human health effects of chlorine, including information from studies with laboratory animals. Where quantitative data were available, the relationship of exposure concentration and exposure duration to toxicity is explained. Emphasis is on acute exposures. 

Several investigators have studied the relationship of exposure duration and exposure concentration as related to the toxic response to airborne chemicals (Flury 1921 Haber 1924 Rinehart and Hatch 1964 ten Berge et al. 1986 ECETOC 1991 and Pieters and Kramer 1994). 

The reference concentration (RfC) methodology to estimate benchmark values for noncancer toxicity of inhaled chemicals was adapted for inhalation studies from the reference dose methodology used for oral exposure assessment. The same general principles were used, but the RfC methodology was expanded to account for the dynamics of the respiratory system as a portal of entry. The reference dose (RfD) methodology included dosimetric adjustments to account for species-specific relationships of exposure concentrations to deposited or delivered doses. Particles and gases are treated separately, and the type of toxicity observed influences the dosimetric adjustment applied to score the exposure concentration for animals to a human equivalent concentration. 

An assessment of the relationship of exposure duration to the development of the adverse event... 

The U.S. Environmental Protection Agency (EPA) divides the health effects of toxic chemicals into two broad categories for risk-assessment purposes risk of noncancer (noncarcinogenic) health effects and risk of cancer (carcinogenic risk) (Chapter 7). The same analysis of exposure is used for both noncarcinogenic and carcinogenic risk however, the relationship of exposure to effect is analyzed differently for noncancer and carcinogenic risks. 

Many of the above types of effects are evident in rodents and monkeys with PbB levels exceeding 30 fig/dl, but some effects on learning ability are apparent even at maximum PbB exposure levels below 20 Hg/d. The problem of extrapolating exposures, and therefore the results of animal research to human populations are discussed in another review by Smith (this volume). Until the function describing the relationship of exposure indices in different species is available, the utility of animal models for deriving dose-response functions relevant to humans may be limited. However, consistent observations of altered behaviour across several species and humans at PbB levels below 30 fig/d tend to converge to indicate lead effects on CNS function at lead levels previously considered safe. ... 

If possible, there should be measurement of the toxic effect in order quantitatively to relate the observations made to the degree of exposure (exposure dose). Ideally, there is a need to determine quantitatively the toxic response to several differing exposure doses, in order to determine the relationship, if any, between exposure dose and the nature and magnitude of any effect. Such dose—response relationship studies are of considerable value in determining whether an effect is causally related to the exposure material, in assessing the possible practical (in-use) relevance of the exposure conditions, and to allow the most reasonable estimates of hazard. 

Dose—response evaluation is used in describing the quantitative relationship between the amount of exposure to a substance and the extent of toxic injury or disease. Data may be derived from animal studies or from studies in exposed human populations. Dose—response toxicity relationship for a substance varies under different exposure conditions. The risk of a substance can not be ascertained with any degree of confidence unless... 

Parent substances and metaboHtes may be stored in tissues, such as fat, from which they continue to be released following cessation of exposure to the parent material. In this way, potentially toxic levels of a material or metaboHte may be maintained in the body. However, the relationship between uptake and release, and the quantitative aspects of partitioning, may be complex and vary between different materials. For example, volatile lipophilic materials are generally more rapidly cleared than nonvolatile substances, and the half-Hves may differ by orders of magnitude. This is exemplified by comparing halothane and DDT (see Anesthetics Insectcontholtechnology). 

Exposure should be by the practical route. Other conditions, such as number and magnitude of exposures, should kiclude at least one level representative of the practical situation monitoring should be appropriate to the needs for conducting the study and when practically and economically possible, pharmacokinetic observations should be undertaken ki order to better define the relationship of dose to metaboHc thresholds. 

The results of the study should allow decisions on whether injury is a direct result of toxicity or secondary to other events. In addition to confirming a causal relationship between exposure to the test material and development of an injury, the study should be reviewed in order to assess whether information is available to determine if the effect is traceable to parent material or metaboUte. 

Air quality criteria are cause-effect relationships, observed experimentally, epidemiologically, or in the field, of exposure fo various ambient levels of specific pollutants. The relationships between adverse responses to air pollution and the air quality levels at which they occur have been discussed in Chapter 4 and illustrated in Table 4-5 and Fig. 4-10. 

The main objective of air quality guidelines and standards is the protection of human health. Since fme particulates (PM,) are more likely to cause adverse health effects than coarse particulates, guidelines and standards referring to fine particulate concentrations are preferred to those referring to TSP, which includes coarse particulate concentrations. Scientific studies provide ample evidence of the relationship between exposure to short-term and long-term ambient particulate concentrations and human mortality and morbidity effects. However, the dose-response mechanism is not yet fully understood. Furthermore, according to the WHO, there is no safe threshold level below which health damage does not occur. 

A toxic reaction may take place during or soon after exposure, or it may only appear after a latency period. Chronic toxicity requires exposure of several years for a toxic effect to occur in humans. With respect to experimental animals, the animals are usually exposed for most or all of their life time to ascertain the occurrence of chronic toxicity. Acute toxic reactions that occur immediately are easy to associate with the exposure and the exposure-effect relationship can readily be demonstrated. The longer the time interval between exposure and effect, the more difficult it is to delineate the relationship between exposure and effect. 

Hazard characterization and delineation of dose-effect or dose-response relationships. 3. Assessment of exposure 4. Risk characterization... 

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories ... 

Dose-response relationship 1 he toxicological concept that the toxicity of a substance depends not only on its toxic properties, but also on the amount of exposure or dose. 

In conclusion, llic purpose of Ihe loxicily assessment is to weigh available evidence regarding the potential for particular contaminants to cause adverse effects in exposed individuals and to provide, where possible, an estimate of the relationship between the extent of exposure to a contaminant and the increased likelihood and/or severity of adverse effects. 

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