Exposure pattern

The Modeling Engine in THERdbASE has the following model groups 1) Population Distributions, 2) Location/Activity Patterns, 3) Food Consumption Patterns, 4) Agent Releases Characteristics, 5) Microenvironment Agent Concentrations, 6) Macroenvironment Agent Concentrations, 7) Exposure Patterns and Scenarios, 8) Dose Patterns, and 9) Risk Assessment. 

The models in the THERdbASE CD are Chemical Source Release, Instantaneous Emission, Chemical Source Release, Timed Application, Indoor Air (2-Zone), Indoor Air (N-Zone), Exposure Patterns for Chemical Agents, Benzene Exposure Assessment Model (BEAM), Source Ba.sed Exposure Scenario (Inhalation + Dermal), and Film Thickness Based Dermal Dose. 

Unlike the requirements for >1 tonne, member states have differing test requirements and formats for Limited Announcement (which must be made in each member state in which the substance is supplied). The requirements for the UK are given in Table 12.9. The test requirements for Base Set (Level 0) are shown in Table 12.10 in addition to these data, the submission dossier should contain the test reports plus chemical specification, intended use, immediate and longer term marketing volumes, a declaration concerning any unfavourable effects of the substance, proposed classification and labelling, and recommended precautions for its safe use. The exact test requirements for Level 1 will be subject to the results of Level 0 and exposure patterns to man and the environment. 

A migration test was developed to simulate human exposure patterns. 5 g of rubber material was cut into 1-2 mm stripes and then immersed in 20 ml of standard test solution of artificial saliva (4.2 g NaHC03, 0.2 g K2CO3, 0.5 g NaCl, 0.03 g NaNO, ad 1000 ml with aqua dest.j. After 24 h incubation at 40 C volatile nitrosamines were determined in an aliquot and determined after destination with a standard technique (GC-TEA-method). 

Although benzene has recently come under increasing control because of its alleged role in leukemia and other neoplastic diseases, in past years it has been widely dispersed in commercial uses and has entered the environment through many routes. In 1977, SRI attempted to characterize "Human Exposures to Atmospheric Benzene" (1). Most of the following examples come from that report, even though several later studies have updated and refined that work, and recent events have changed exposure patterns. 

Because notices for many new substances do not contain sufficient information and data for evaluating their toxicities (especially re chronic effects) and probable exposure patterns, EPA s primary focus in reviewing PMN s has been to determine whether it will request further testing. In some cases, the exercise (or threat of exercise) of the Agency s authority has proven sufficient to persuade a company either to hold up production of the substance voluntarily (while further data are developed), or to cease altogether its plans for bringing the chemical to market. 

Knowledge of exposure pathways is a critical part of the analysis needed to piece together the human exposure pattern. 

Regulatory agencies also attempt to develop more realistic estimates, but this is difficult, and a scientific consensus on just what exposure pattern should be presumed desirable for risk assessment is not available, except for a few circumstances (food additives, human drugs, and a few others). Much attention is now focused on methods to develop information on the full distribution of exposures in a population, but this can be technically difficult to achieve. 

The systematic evaluation of substance properties and predictable or actual exposure patterns over the entire life-time of a substance within the scope of risk assessment is as yet a relatively recent instrument, for which harmonised scientific rales were created in the EU for the first time in 1997 in the form of the Technical Guidance Documents (TGD). An essential element in this range of instruments is how to deal with shortcomings in knowledge. Wherever information is missing, standardised worst-case scenarios are conceived taking into account appropriate safety factors . If under these worst-case assumptions a rele-... 

Dose and end point used for MRL derivation The minimal LOAEL of 188 mg/kg/day was used to derive the MRL. This concentration was normalized to 134 mg/kg/day by adjusting for a 5 days a week exposure pattern. 

Differences between experimental conditions and exposure patterns for workers chronic-to-chronic exposure, a default value of 1 subacute-to-subchronic exposure, a default value of 10 subchronic-to-chronic exposure, a default value of 10 other aspects, a default value of 1... 

Children s exposure pattern differs from that of adults and children may be more heavily exposed than adults to certain chemicals in the environment as they, on a body weight basis, breathe more air, drink more water, and eat more food than adults additionally, their behavior patterns, such as play close to the ground and hand-to-mouth activities, can increase their exposure. The differences in exposure patterns between children and adults are often used as an argument for increased susceptibility of children to chemicals however, it should be recognized that such differences are not related to increased vulnerability to chemicals but are purely related to an increased internal exposure (Nielsen et al. 2001). 

Toxicokinetic data The major factors responsible for differences in toxicity due to route of exposure include (1) differences in bioavaUabUity (absorption), (2) differences in metabolism (e.g., first-pass effects), and (3) differences in internal exposure pattern (kinetics). 

Henderson RF, Barr EB, Cheng YS, et al The effect of exposure pattern on the accumulation of particles and the response of the lung to inhaled particles. Fundam Appl Toxicol 19 367-374, 1992... 

Mismatch between exposure pattern over time in laboratory and field Nondietary routes of exposure (e.g., dermal exposure and inhalation)... 

Fig. 15 Schematic implementation of quantum lithography with photon pairs generated in SPDC. Two-photon absorbing photoresist is used as a recording medium. SPDC signal and idler photons are overlapped on a beamsplitter, and exit either of its output ports together. Exposure patterns due to classical and quantum interference are shown in the long and short amplitudes, respectively...

Once the field technician has exposed and analyzed his supply of samplers, his kit can be replenished in the home lab or replacement items can be sent to him. Likewise, the data compiled is sent to the home office where it is analyzed for exposure patterns as a function of operational procedures before being incorporated into employee health history files. 

Exposure patterns as well as developmental characteristics change as the child matures, and this must be taken into account. Both biological and behavioural changes affect the potential for exposure (reviewed in Cohen-Hubal et al., 2000). For example, small children mouth toys that may contain harmful chemicals. Children s diets are different, including liquid intake. Because of differences in metabolism, they may reach higher levels with a given exposure than those for adults. This combination of exposure and outcome complexities makes assessment of childhood developmental toxicity an extremely difficult endeavour. 

A weight of evidence approach to assessing reproductive toxicity requires rigorous evaluation of all available data. However, often only limited information is available, and default assumptions must be made because of uncertainties in understanding mechanisms, dose-response relationships at low dose levels and human exposure patterns. Several of these assumptions are basic to the extrapolation of toxicity data from animals to humans, while others are specific to reproductive toxicity. The general default assumptions for reproductive toxicity stated in the IPCS (1995) report are summarized as follows ... 

Through functional-use analysis, toxicological and environmental fate data on structurally similar chemicals can be applied to each member of a functional-use class. A focus on functional use not only offers commonality in perspective for chemical innovators, but also simplifies the risk assessment process. Within a given product dass, the use and exposure patterns are generally the same, with minor variability therefore, the hazard component of the risk equation becomes a... 

The inhalation RfC for naphthalene was 0.003 mg/m3, and this RfC was derived from a chronic (2-year) NTP inhalation study in mice using exposures of 0, 10, or 30 ppm (NTP, 1992). Groups of mice were exposed for 5 days a week and 6 hours a day. This study identified a LOAEL of 10 ppm. A dose-related incidence of chronic inflammation of the epithelium of the nasal passages and lungs was observed. This LOAEL concentration was normalized by adjusting for the 6-hour-per-day and 5-day-per-week exposure pattern. A LOAEL of 9.3 mg/m3 was obtained was derived by converting 10 ppm first to mg/m3 and then duration-adjusted levels for 6 h/day and 5 days/week for 103 weeks. An UP of 3000 was used, where 10 was for the interspecies (mice to humans) extrapolations, 10 for intraspecies variation in humans, 10 for using a LOAEL instead of a NOAEL, and 3 for database deficiencies. 

There are several interesting features of the phthalate biomarker-exposure dose analyses. First, women and children have greater exposure to several phthalates than male adults. That may be due to the use of cosmetics and personal-care products in the case of women and due to higher food intake rate per body weight and exposure to plasticizers in toys in children. Data on children younger than 6 years old are not available, and this may be an important data gap. The other feature of note is that the relatively small German study found exposures to some phthalates that were 3-20 times above those found in the United States, whereas for other phthalates the exposure differential was smaller and concentrations in the United States were greater (Koch et al. 2003). That implies a different exposure pattern in different countries. 

Another uncertainty in the children s MOE analysis is that the biomonitoring data showed that perfluorooctanoates related to PFOA—per-fluorohexansulfonate and N-methyl perfluorooctanesulfonamidoacetate— were considerably higher in children than in adults. The reason is unknown, but the original authors suggest that it may reflect a different exposure pattern in children (Olsen et al. 2004). Toxicology and exposure data on these analytes are not sufficient to enable a separate risk assessment to evaluate the children s exposures. 

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