Proof of exposure

The ICH guidehne requires that there must be proof of exposure of the target tissues to the test compoimd (and its metabolites) to vaHdate the chosen in vivo assays. 

Blood samples can also be obtained from fetuses removed by caesarean section on the last day of dosing for proof of exposure. 

Generally, GC is a very suitable technique for the analysis of these volatile substances and the definitive proof of exposure to them is their detection in biological fluids and tissues. All the commonly abused solvents can be detected in the headspace from 200 pi of blood. Toluene could be detected by MS in the breath of known glue sniffers up to 4 days after the last episode. GC and GC-MS were used to determine toluene in various tissues and blood in a... 

A positive result is a proof of exposure but not of disease nor even an absolute proof of a causal relationship between exposure and disease. Mineralogical analysis is only one factor in the attribution of a disease to a particular exposure. Determining whether an element or mineral is responsible for a disease process depends on appropriate clinical, radiological and pathological findings (Churg and Green 1998). 

An airspace heater ejects steam into the airspace above the product and into the foam, maintaining a temperature at least 5°C above the minimum hoi ding temperature of 63°C. The time—temperature exposure is recorded on a chart which must be kept for proof of treatment. If the Hd is opened, and the milk temperature falls below 63°C, the exposure is intermpted causing the pasteurization cycle to restart. 

Repeated exposure to ethyl alcohol results in the development of a tolerance as evidenced by decreasing symptomatic reactions. It has been demonstrated that the symptoms of exposure are less clear and the time required to produce them is greater in subjects accustomed to alcohol. There is no proof, however, of physiological adaptation in humans in terms of metaboHc changes or resistance to cellular injuries. The subject of the interaction of alcohol with other dmgs has received much attention (277). 

The moisture content of a plastic affects such conditions as electrical insulation resistance, dielectric losses, mechanical properties, dimensions, and appearances. The effect on the properties due to moisture content depends largely on the type of exposure (by immersion in water or by exposure to high humidity), the shape of the product, and the inherent behavior properties of the plastic material. The ultimate proof for tolerance of moisture in a product has to be a product test under extreme conditions of usage in which critical dimensions and needed properties are verified. Plastics with very low water-moisture absorption rates tend to have better dimensional stability. 

If these methods do prove inconclusive, biomedical sample analysis may provide a unique method for establishing exposure. Due to both the complex technical requirements and the strict forensic approach used it is unlikely that this information will be available in the early phases of response to such an incident. Biomedical sample analysis does however offer another method by which proof of the use of chemical agents can be provided, and thus has a potentially significant role in the overall preparation of a capability for the response to a terrorist chemical agent attack. 

Effect of Dose and Duration of Exposure on Toxicity. No studies were located where -hexane concentration was measured in workplace air before workers became ill, so no dose-response relationship can be defined for human neurotoxicity as the result of -hexane exposure. Information on duration of exposure leading to toxicity is available from some case series reports. An occupational exposure caused sensory disturbances in the lower extremities after approximately 2 months (Herskowitz et al. 1971). A case of peripheral neuropathy after 7 months of exposure was reported among press-proofing workers in Taipei (Wang et al. 1986) a serious case resulting in quadriplegia after 8 months of exposure was reported among sandal workers in Japan (Yamamura 1969). Based on case reports, it can be estimated... 

In the United States, the National Center for Toxieogenomies (NCT) has eondueted some proof-of-prineiple experiments to establish signature profiles of known toxieants, and to link the pattern of altered gene expression to speeifie parameters of eonventional indiees of toxieity (4,47,48). These studies have shown that it is possible to identify a signature of expressed gene patterns after exposure to a given toxieant (49). 

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