Exposure dose, calculation inhalation

Mathematical modelling of the dose-response relationship is an alternative approach to quantify the estimated response within the experimental range. This approach can be used to determine the BMD or benchmark concentration (BMC) for inhalation exposure, which can be used in place of the LOAEL or NOAEL (Crump, 1984). The BMD (used here for either BMD or BMC) is defined as the lower confidence limit on a dose that produces a particular level of response (e.g., 1%, 5%, 10%) and has several advantages over the LOAEL or NOAEL (Kimmel Gaylor, 1988 Kimmel, 1990 USEPA, 1995 IPCS, 1999). For example, (1) the BMD approach uses all of the data in fitting a model instead of only data indicating the LOAEL or NOAEL (2) by fitting all of the data, the BMD approach takes into account the slope of the dose-response curve (3) the BMD takes into account variability in the data and (4) the BMD is not limited to one experimental dose. Calculation and use of the BMD approach are described in a US EPA... 

Pharmacokinetic calculations yielded estimates of chlorpyrifos intake of 0.05-1 pg/kg per day in the general population. The model estimates compare favorably with pathway analysis estimates of aggregate chlorpyrifos exposure from numerous dose routes, including indoor inhalation, dermal contact, and food ingestion (Shurdut et al. 1998 Pang et al. 2002). The calculated exposure doses ranged from 0.02 to 1 pg/kg per day. Further... 

An analysis of the calculation results shows that, if using the conservative approach (time of NS waterborne storage prior to dismantlement 5 years, that of storage after dismantlement 0 years), imder the taken assmnptions effective exposure doses would be approximately the same for all professional groups equaling 20 pSv/year. The main contribution to the exposure dose would be due to inhalation intake of radionuclides with marine aerosols. 

Pulmonary retention (net respiratory uptake) of MTBE in volunteers exposed to concentrations ranging from 5 to 75 ppm is around 40%, while pulmonary retention of ETBE over an exposure range of 5 to 50 ppm is about 26% [35]. About 7-9% of the inhaled MTBE is reversibly taken up by the mucous membranes of the upper airways [31]. The internal dose calculated from the area under the inhaled air concentration and alveolar breath concentration curves, after inhalation exposure to 1.7 ppm for 15 min [26], averaged 197 50 pg for all subjects (about 3.86 pg/kg bw). 

The acute lethal toxicity of anti-ChEs by inhalation exposure is usually the result of a combination of both local anti-ChE effects on the respiratory tract and. systemic effects from absorbed anti-ChE. Acute lethal toxicity can be numerically expressed as either timed LC50 (i.e., the concentration of material in the exposure atmosphere, calculated from the analytically measured exposure concentration-mortality data, that will be lethal to 50% of the species exposed for a set exposure time e,g., mg for an exposure of x hours) or as the inhalation exposure dose (concentration X exposure time CT). which is lethal to 50% of the exposed. species, the L(CT)jo. This is expressed as the product of exposure time and concentration (e.g., mg min m ). The former method of citing lethality data is preferred, providing the exposure time is kept constant for the various exposure concentrations, since it gives a directly useable value for lethal hazard evaluation and permits a ready comparison between different materials. In the case of L(CT)50 values, however, this does not... 

As an example, suppose that in a routine monitoring programme, with a monitoring period of 14 days, a thyroid content of 3000 Bq is detected in a male worker. Because of the operations under way in this workplace, it is assumed that aiy exposures will be due to inhalation of a particulate rather than vapour form (although for this assumption is not critical). Similarly, intakes by ingestion would also lead to the same pattern of retention and exeretion [8,9], and the same committed effective dose calculated from the monitoring data. 

The TGD has noted that in practice, relevant data on kinetics and metabolism, especially after dermal and inhalation exposure, are frequently missing. As a consequence, corrections can only be made for differences in bioavailability. There are some pragmatic approaches in order to calculate a NAEL (or LAEL) by extrapolation, when specific data are not available. The methods described are for extrapolating from oral toxicity data since this is the route most often used for repeated dose toxicity studies in animals. The TGD emphasized that it should be noted that insight into the reliability of the current methodologies for route-to-route extrapolation has not been obtained yet, with a reference to the smdy performed by WUschut et al. (1998), see above. 

LDso/Lethal Dose Fifty—A calculated dose expected to cause the death of 50% of a tested population from exposure by any route other than inhalation. 

Calculating the dose following workplace or environmental exposure can be far more difficult. If the agent is in the air, then calculation of the dose must consider not only the concentration in the air but also the duration of the exposure, rate of breathing, and body weight. The amount of air inhaled over a period of time is... 

The ERA has calculated a subchronic oral reference dose (RfD) of 7x10 mg/kg/day for carblon tetrachloride based on a NOAEL of 1 mg/kg/day (converted to 0.71 mg/kg/day based on intermittent exposure) for rats in a 12-week study (Bruckner et al. 1986 ERA 1989b IRIS 1993). The critical effect was liver toxicity. A chronic oral RfD of 7x10 mg/kg/day was also calculated based on the same NOAEL used for the subchronic RfD. The ATSDR has calculated an acute inhalation MRL of 0.2 ppm based on a LOAEL of 50 ppm for liver effects in an acute 4-day rat inhalation study (David et al. 1981), and an intermediate inhalation MRL of 0.05 ppm based on a NOAEL of 5 ppm for liver effects in an intermediate-duration (187-192 days) inhalation study in rats (Adams et al. 1952). The ATSDR has also calculated an acute oral MRL of 0.02 mg/kg/day based on a LOAEL of 5 mg/kg/day over 10 days for liver effects in the rat (Smialowicz et al. 1991), and an intermediate oral MRL of 0.007 mg/kg/day based on a NOAEL of 1 mg/kg/day over 12 weeks (converted to 0.71 mg/kg/day based on intermittent exposure) for liver effects in the rat (Bruckner et al. 1986). 

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