Chronic exposure defined

Acceptable Intake for Chronic Exposure (AIC) An estimate similar in concept to the RfD but derived using a less strictly defined methodology. Chronic RfDs have replaced AICs as the Agency s preferred values for use in evaluating potential noncarcinogenic health effects resulting from chronie exposure to a chemical. 

Eor the purpose of assessing the remaining interspecies uncertainty, Vermeire et al. (1999) collected and analyzed data for 184 chemicals tested in different species and via different exposure routes. NOAELs were selected from studies with mice, rats, and dogs exposed to the same chemical via the same exposure route and with the same duration of exposure. Two categories of exposure duration were defined, subacute and (sub)chronic, in order to increase the comparability of the different studies. The definition of these exposure categories is species specific, partly depending on their maximum lifetime. Subacute exposure was defined as 21-50 days for the mouse and rat, and as 28-90 days for the dog (sub)chronic exposure was defined as 90-730 days for the mouse and rat, and as 365-730 days for the dog. The oral NOAELs were adjusted to account for differences in metabolic size, i.e., by the caloric requirement approach (Section 5.3.2.3). 

WHO/IPCS (1994, 1996, 1999) did not consider an extrapolation factor for duration of exposure specifically, but the uncertainty related to this element is included in a broader defined additional factor addressing the adequacy of the overall database (Section 5.9). The US-EPA (1993) has adopted the 10-fold factor to account for the uncertainty involved in extrapolating from less than chronic NOAELs to chronic NOAELs. This default value has later on been reconfirmed (US-EPA 2002) when only a subchronic duration smdy is available to develop a chronic reference value no chronic reference value is derived if neither a subchronic nor a chronic smdy is available. For systemic effects, ECETOC (2001) recommended a default assessment factor of 6 for extrapolation from subacute (28 days) to chronic exposure, and a factor of 2 from subchronic (90 days) to chronic exposure. For local effects, no additional assessment factor is needed for duration of exposure extrapolation for substances with a local effect below the threshold of cytotoxicity. KEMl (2003) suggested that extrapolation from subchronic to chronic exposure should be based on the distribution of NOAEL ratios reported by Vermeire et al. (2001) with an assessment factor of 16 covering 95% of the substances compared and for extrapolation from subacute to chronic exposure, with an assessment factor of 39 covering 95% of the substances. 

Immunotoxicity. No information on immunotoxicity after exposure to 1,3,5-TNB by any of the three routes is available in humans or animals. Therefore, animal studies following acute, intermediate, and chronic exposure to 1,3,5-TNB via all three routes would help in estimating the potential immunotoxic effects in humans. Spleen enlargement was reported in acute-(Blackburn et al. 1988) and intermediate-duration (Cody et al. 1981 Linder et al. 1986) studies in animals. These effects, however, were secondary to adverse hematological effects. Studies in laboratory animals following acute exposure to 1,3-DNB by the oral route would help define possible effects on antibody production and cellular immunity. This information could be used to determine populations sensitive to possible exposure to 1,3-DNB at locations close to ammunition plants or in specific workplaces. 

Skeletal fluorosis can be defined as excessive deposition of fluoride in bone. This is a pathological condition that is by far the most important aspect of chronic exposure to elevated levels of fluoride, either by inhalation or by ingestion. The skeletal deformities may be associated with or accentuated by nutritional deficiencies or even malnutrition and hard manual work or, possibly, other conditions found in areas of long-term social and nutritional deprivation [6]. See, for instance Fig. 1 of [54]. The situation is specific also for populations consuming large volumes of water, such as athletes or people with certain medical conditions or... 

Chronic toxicity defines a specific dose or exposure level that will produce measurable, long-term toxic effects, including carcinogenicity. 

All of the previously mentioned exposure methods can be used to estimate either chronic exposure (over a period of years) or acute exposure (single day) for the United States population and population subgroups. Both chronic and acute assessments are usually based on a no observed adverse effect level (NOAEL) in an animal species. Acute exposure is defined relative to an acute (single dose) toxicological endpoint (usually a NOAEL) and may be expressed as a margin of exposure (MOE) or as a percentage of an acute reference dose that is based on a NOAEL and an uncertainty factor (see below). 

In the 1998 Draft for Public Comment, an MRL of 0.0001 mg chromium(VI)/m3 had been derived for both intermediate and chronic exposures as chromium trioxide mist and other dissolved hexavalent chromium aerosols and mists. This MRL was also based on the study Lindberg and Hedenstiema (1983), but an exposure level of 0.001 mg chromium(VI)/m3 had been considered a NOAEL, and there had been no adjustment from intermittent to continuous exposure. Further evaluation of this study indicated that a NOAEL could not be clearly defined therefore, the LOAEL of 0.002 mg chromium(VI)/m3 was selected and adjusted for continuous exposure for the concern that the nasal lesions could accumulate at a greater rate than the repair mechanisms. The MRL of 0.000005 mg/m3 no longer applies for chronic exposure because concern that carcinogenicity associated with chronic exposure to hexavalent chromium compounds takes precedence. 

HRAs are a means of estimating the potential for an adverse effect on a select population upon exposure to a single chemical or mixture of chemicals. This risk is generally defined as a function of the concentration of chemical(s) to which an individual of known size and specified characteristics is exposed, for a given period of time, via ingestion, inhalation, or dermal contact. HRAs are performed for acute and chronic exposures of both on-site and off-site populations. 

Occupational exposure is defined as chronic exposure in amounts less than the threshold limit value causing material symptoms. As with many teratogens, critical... 

While lung cancer and mesothelioma are generally associated with chronic exposure to asbestos, there are several studies that indicate that short-term exposures are also of concern. For example, it has been noted that workers exposed to asbestos for only 1-12 months had an increased risk of developing lung cancer a number of years later. In animals, mesotheliomas developed in two rats exposed to high concentrations of amosite or crocidolite for only 1 day. These data are not extensive enough to define the dose- or time-dependency of health risks from short-term exposure to asbestos, but the data do indicate that short-term exposures should not be disregarded. 

A wide variety of morphological changes have been associated with inhalation of airborne contaminants. Both acute and chronic exposures directly affect the structural integrity of the respiratory system. Acute studies are conducted primarily to define the intrinsic toxicity of the chemical, to identify the target organs, and provide information for the design and selection of doses for long-term studies. 

Aged Rat Inhalation Route. Groups of 24 aged rats (18 months old purchased by the contractor) of each sex shall be exposed to decalin/ tetralin vapor for 6 hours using the proposed middle chronic exposure concentration via inhalation route. Immediately after shutdown of the exposure, the decline of blood concentrations of decalin/tetralin shall be followed at eight time points (to be determined based on the results of the preliminary study), with three animals bled at each time point. The first time point shall be as close as possible to time zero. Time zero is defined as the time of shutdown of the chamber exposure. Each rat shall be sampled only once. Blood concentrations of decalin/ tetralin shall be determined using the validated analytical method. 

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