Risk assessment inhalation

Personal exposure Predictions of exposure of occupants to airborne contaminants for risk assessment, inhaled doses, or time-integrated concentration values. 

Schlesinger RB, Cassee F (2003) Atmospheric secondary inorganic particulate matter the toxicological perspective as a basis for health effects risk assessment. Inhal Toxicol 15 197-235... 

McClellan RO. Lung cancer in rats from prolonged exposure to high concentrations of carbonaceous particles implications for human risk assessment. Inhal Toxicol 1996 8(suppl) 193-226. 

In health risk assessment, the carcinogenic risk calculation by inhalation (IR) can be calculated by ... 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

Monte Carlo simulation, an iterative technique which derives a range of risk estimates, was incorporated into a trichloroethylene risk assessment using the PBPK model developed by Fisher and Allen (1993). The results of this study (Cronin et al. 1995), which used the kinetics of TCA production and trichloroethylene elimination as the dose metrics relevant to carcinogenic risk, indicated that concentrations of 0.09-1.0 pg/L (men) and 0.29-5.3 pg/L (women) in drinking water correspond to a cancer risk in humans of 1 in 1 million. For inhalation exposure, a similar risk was obtained from intermittent exposure to 0.07-13.3 ppb (men) and 0.16-6.3 ppb (women), or continuous exposure to 0.01-2.6 ppb (men) and 0.03-6.3 ppb (women) (Cronin et al. 1995). 

SADA provides a full human health risk assessment module and associated databases. The risk models follow the USEPA s Risk Assessment Guidance for Superfund (RAGS) and can be customized to fit site-specific exposure conditions. It calculates risks based on the following exposure pathways ingestion, inhalation, dermal contact, food consumption, and also a combined exposure. 

Hofmann, W., Cellular Lung Dosimetry for Inhaled Radon Decay Products as a Base for Radiation - Induced Lung Cancer Risk Assessment. Radiat. Environ. Biophys. 20 95-112 (1982). 

Hofmann, W., Lung Cancer Induction by Inhaled Radon Daughters-What is the Relevant Dose , in Radiation Protection Dosimetry, Indoor Exposure to Natural Radiation and Associated Risk Assessment, (Clemente, G., F. et al, eds), pp.367-370, Nuclear Technology... 

The Food Quality Protection Act (FQPA) of 1996 mandated that the US EPA carry out risk assessments that consider the cumulative effects of exposure to pesticides having a common mechanism of toxicity, as well as consider exposure to each pesticide by various routes of exposure (e.g., dermal, dietary, inhalation) and sources (e.g., residues in food and water) in an aggregate manner [19]. To accomplish this, there needs to be sufficient evidence supporting a common adverse effect that is associated with a common mechanism of action in specific target tissues. To date, the required criteria necessary to establish a common mechanism of toxicity with a specific toxic effect for the pyrethroids are not available [1,8,98]. 

Risk assessment. The Perbellini model successfully described alveolar air and venous blood concentrations of -hexane following inhalation exposure in humans. Simulations indicated that exposure to 50 ppm for an 8-hour-workday, 5-day workweek would result in a gradual accumulation of -hexane in body fat which is not completely cleared during the weekend. 

A case can often be made to omit studies as scientifically unnecessary, because it is possible to conduct an adequate risk assessment without them. This is most often the case if the substance decomposes to degradants of known hazardous properties. For example the substance may hydrolyse rapidly to non-toxic products, so the key issue is to establish that this happens rapidly in the stomach before the parent substance can be absorbed. There may then be a case for omitting the expensive long-term animal studies, providing it is also established that there is no dermal or inhalation absorption from these exposure routes. In a similar way, it may be justified to omit ecotoxicity studies on a substance which hydrolyses or otherwise decomposes in the aquatic environment to stable products that have already been tested. 

There are no occupational exposure limits for many hazardous substances which may require control of inhalation exposures. The necessary data and other resources required for setting such limits is restricted and unlikely to match the potential demand. A hazard categorisation scheme was, therefore, developed for application within the chemical industry. The scheme used readily-available information on toxicological endpoints to place hazardous substances into a limited range of hazard categories, expressed as Occupational Exposure Bands. These Bands could be used as a basis for risk assessment and the selection of appropriate control regimes. 10 refs. EUROPEAN COMMUNITY EUROPEAN UNION UK WESTERN EUROPE... 

AALAC certified laboratory. In-housing testing included acute, subacute, and subchronic oral, dermal and inhalation studies and specialty reproductive, behavioural, haematological and renal function toxicity studies. Preparation of risk assessment, submissions and presentations to regulatory agencies and trade association. 

Kuempel ED, Tran CL, Castranova V, Bailer AJ (2006). Lung dosimetry and risk assessment of nanoparticles evaluating and extending current models in rats and humans. Inhal. Toxicol. 18 717-24. 

The bioavailability of contaminants to wildlife and humans is also an area of critical importance, where contaminants can be taken up in pore water and by dermal contact, particle ingestion, or particle inhalation. The dynamics of sorption/desorption are not currently incorporated into exposure and risk assessment models for organic compounds, where availability, in most cases, is assumed to be 100% [224]. Recently, the following have been demonstrated and reported ... 

In some cases the available dose-response data will have originated from studies by one route of exposure (say, inhalation), but the population of interest is or might be exposed by other routes, say the oral one. Completion of a risk assessment prior to the development of new oral data will require a biologically justifiable method for extrapolating results from one route of exposure to another. 

Risk Assessment. The McKone model has some use in human chloroform risk assessments, in that the model defined the relationship between the dermal and inhalation exposure to measures of dose and the amounts that can be metabolized by the liver by each route. The model also provided information about the inhalation and dermal exposure concentrations at which chloroform metabolism becomes nonlinear in humans. 

The model was also used to assess the relationship of dermal and inhalation exposure to metabolized dose in the liver, as well as to determine the tap-water concentrations at which hepatic metabolism of dermal and inhalation doses of chloroform become nonlinear. This information is especially useful for risk assessment on persons exposed to a wide range of chloroform concentrations. Experimentally measured ratios of chloroform concentrations in air and breath to tap water concentration (Jo et al. 1990a) were compared with the model predictions. 

Many laboratory animal models have been used to describe the toxicity and pharmacology of chloroform. By far, the most commonly used laboratory animal species are the rat and mouse models. Generally, the pharmacokinetic and toxicokinetic data gathered from rats and mice compare favorably with the limited information available from human studies. PBPK models have been developed using pharmacokinetic and toxicokinetic data for use in risk assessment work for the human. The models are discussed in depth in Section 2.3.5. As mentioned previously, male mice have a sex-related tendency to develop severe renal disease when exposed to chloroform, particularly by the inhalation and oral exposure routes. This effect appears to be species-related as well, since experiments in rabbits and guinea pigs found no sex-related differences in renal toxicity. 

Larson JL, Templin MV, Wolf DC. 1996. A 90-day chloroform inhalation study in female and male B6C3Fi mice Implications for cancer risk assessment. Fundamental and Applied Toxicology 30 118-137. 

McKee R, Freeman J. 1993. Dermal carcinogenicity studies of petroleum-derived materials. In RGM Wang, JB Knaak, HI Maiback, eds.. Health Risk Assessment Dermal and Inhalation Exposure and Absorption of Toxicants CRC Press, Ann Arbor MI, 263-21 A. 

Distribution, including accumulation of an absorbed substance, will be the same irrespective of the route of administration. However, distribution and accumulation at the site of apphcation (inhalation, oral, dermal) may depend on the route of administration. In such cases, local accumulation may occur and may be responsible for tissue damage. In these cases, systemic toxicokinetics of the substance may be of limited relevance for the risk assessment. It is generally not cmcial for risk assessment to determine the precise tissue distribution profile for a substance. In certain special cases, however, specific tissue distribution studies may assist or even be essential for the interpretation of available toxicological data. For example, it may be of interest to know whether the substance will cross the blood-brain barrier, the placenta barrier, or will accumulate in specific tissues. 

Risk characterization is thus the step in the risk assessment process where the outcome of the exposure assessment (e.g., daily intake via food and drinking water, or via inhalation of airborne substances) and the hazard (effects) assessment (e.g., NOAEL and tolerable intake) are compared. If possible, an uncertainty analysis should be carried out, which produces an estimation of the risk. Several questions should be answered before comparison of hazard and exposure is made ... 

Whalan J.E. and H.M. Pettigrew. 1997. Inhalation risk assessments and the combining of margins of exposure. Washington, DC U.S. Environmental Protection Agency, Office of Pesticide Programs. 

Risk assessment and epidemiology could be successfully combined to analyze environmental health risks. Exposure assessments estimate concentrations of toxic chemicals in the environment that could be transferred to humans by ingestion, inhalation, or dermal absorption. In the future, there will be a greater need for agreement on how best to simultaneously assess societal risks involved with damage to both ecosystems and the human population (Ruttenber, 1993). 

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