Exogenous hazards

Cancer. Studies found no relationship between endogenous p-cresol levels in the urine and the occurrence of large bowel cancer (Bone et al. 1976) or bladder cancer (Renwick et al. 1988) in humans. There are no data available regarding the carcinogenicity of exogenous cresols in humans. No cancer bioassays have been conducted in animals, but the results of a promotion study in mice suggested that cresols can be cancer promoters. Cresols have some ability to interact with mammalian DNA in vitro, but it is impossible to assess the potential hazard to humans without more information. 

Autocatalytic decompositions are common in fine chemistry [1]. They are considered hazardous because they give rise to sudden heat evolution, often with unexpected initiation and unknown exogenic influences [2], consequently they are often perceived as unpredictable. The sudden heat evolution stems from the special nature of the reaction kinetics and results in a violent reaction often associated with important destructive power. For these reasons, it is worth dedicating a special chapter to autocatalytic reactions. 

The initial idea is to use the differential equations of a probabilistic transfer model with hazard rates varying with the age of the molecules, i.e., to enlarge the limiting hypothesis (9.2). The objective is to find nonexponential families of survival distributions that are mathematically tractable and yet sufficiently flexible to fit the observed data. In the simplest case, the differential equation (9.7) links hazard rates and survival distributions. Nevertheless, this relation was at the origin of an erroneous use of the hazard function. In fact, substituting in this relation the age a by the exogenous time t, we obtain... 

Postulate 2. The degree of completeness of the set of internal restraints and exogenous factors specifying a hazardous system and its transformation, determines the degree of completeness with which the pathways leading to a hazardous state can be identified. 

Local skin effects are not the only consideration for dermal toxicity. The role of the skin as a barrier preventing the free penetration of exogenous chemicals into the systemic circulation is equally important. Indeed, it is becoming apparent that the dermal route of exposure is in many cases comparable to inhalation and oral absorption as a potential source of potentially toxic chemicals in the body and forms an integral part of many multi-media multi-pathway risk assessments. In this context, for example, the (US) National Institute of Occupational Safety and Health is currently revising its current skin notations (which identify chemicals likely to present dermal hazards in the workplace) to take into account a... 

Methods that involve studying the disposition of some exogenously administered agent (e.g. indocyanine green, antipyrine, galactose or dextromethorphan) have now been superceded by functional (often multicomponent) tests. Mono-ethylglycinexylidide formation has not found wide acceptance. More complicated Cox proportional hazards models may exist for other liver diseases, but are only used specifically for them (e.g. the Mayo Clinic Survival Model for primary biliary cirrhosis see the US FDA Guidance). 

When we look at any system we can distinguish between two distinct groups of hazards endogenous and exogenous - see Table 6.1 (which is a useful reminder to consider hazards resulting from causes outside the system s boundary). 

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