Toxicity route-specific

Immunotoxicity. Only a single case report of skin allergy to methyl parathion has been reported in humans (Lisi et al. 1987). No studies are available in humans exposed to methyl parathion via the inhalation or oral route. Based on limited animal studies, immunotoxicity may be a sensitive end point of methyl parathion-induced toxicity (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). Thus, humans may be at risk for adverse immunological effects following exposure to methyl parathion. The limited information available on the effects of combined exposure to methyl parathion suggest the its toxicity is not route-dependent. Therefore, there is no reason to suspect that the immunotoxic effects observed following oral exposure of animals are route-specific. 

The database for the health effects of endosulfan following ingestion in experimental animals is substantial. However, as can be seen in Figure 2-5, somewhat less information is available on the effects of inhalation and dermal exposure to endosulfan in animals. Furthermore, the health effects associated with acute- and intermediate-duration inhalation and dermal exposure are more fully characterized than those associated with chronic inhalation or dermal exposure. There is no evidence suggesting that the toxicity of endosulfan is route-specific. However, ingested endosulfan should reach the liver sooner. 

No intermediate-duration dermal studies of hydrogen sulfide were identified. As significant human dermal exposure to hydrogen sulfide is unlikely, dermal exposure studies should not be a high priority. However, no pharmacokinetic data are available that might support the identification of target organs across routes of exposures in the absence of route-specific toxicity data. 

The human data suggest that the immune system is a target of white phosphorus toxicity however, no information on the potential of white phosphorus to impair immune function is available. Animal studies assessing the results of a battery of immune function tests could be useful in determining the immunotoxic potential of white phosphorus. Information on different routes of exposure could be useful in assessing if effects are route specific. 

Probabilistic risk assessment methods are described herein for determining a popnlation s distribution of the dose from exposure and the combination of that exposnre characterization with appropriate toxicological information to form aggregate and cumulative risk assessments. An individual s dose from exposure is characterized as a set of chemical- and route-specific dose profiles over time. Toxic equivalence factors (TEFs) that reflect the toxic endpoint and exposure duration of concern are used to scale chemical- and route-specific doses to toxic equivalent doses (TEDs). The latter are combined in a temporally consistent manner to form a profile over time of the Total TED. For each individual, a Total MOE is calculated by dividing a toxicologically relevant benchmark dose (e.g. an EDio) by the individual s Total TED. The distribution of the Total MOE in a popnlation provides important information for risk management decisions. 

The long term objective of our work is to examine the applications of LC-MS in measuring human exposure to toxic substances. Specifically, we are investigating the direct measurement of polar and ionic metabolites of toxic compounds in the urine. Common mammalian metabolic routes include conjugation with glucuronide or sulfate moieties (9), and such conjugates are difficult to analyze by GC without extensive sample preparation (10, H). The model compounds chosen for this study and their typical parent compounds are shown in Table I. 

Just as zinc deficiency has been associated with adverse effects in humans and animals, overexposures to zinc also have been associated with toxic effects. This chapter contains a description of the toxic effects that have been associated with exposures to high levels of zinc and selected zinc compounds by the inhalation, oral, and dermal routes. Specifically, zinc chloride, zinc oxide, zinc sulfate, and zinc sulfide will be considered. Other zinc compounds are discussed in this chapter whenever data regarding these compounds add relevant information to the discussion on zinc. Any general comments regarding the lack of data on zinc refer to both zinc and its compounds. 

Ha2ard is the likelihood that the known toxicity of a material will be exhibited under specific conditions of use. It follows that the toxicity of a material, ie, its potential to produce injury, is but one of many considerations to be taken into account in assessment procedures with respect to defining ha2ard. The following are equally important factors that need to be considered physicochemical properties of the material use pattern of the material and characteristics of the environment where the material is handled source of exposure, normal and accidental control measures used to regulate exposure the duration, magnitude, and frequency of exposure route of exposure and physical nature of exposure conditions, eg, gas, aerosol, or Hquid population exposed and variabiUty in exposure conditions and experience with exposed human populations. 

Safety valve releases are routed to blowdown drums when the presence of liquid, toxic properties or other factors would make discharge to the atmosphere hazardous. Product and intermediate process streams may need to be diverted to alternative disposal if they are off-specification (e.g., during startup) or in the event of emergency shutdown of downstream equipment. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

As discussed earlier, selectivity is the consequence of the interplay between toxicokinetic and toxicodynamic factors. Some examples are given in Table 2.8, which will now be briefly discussed (data from Walker and Oesch 1983, and Walker 1994a,b). These and other examples will be described in more detail under specific pollutants later in the text. In the table, comparisons are made between the median lethal doses or concentrations for different species or strains. Comparisons are made of data obtained in lethal toxicity tests where the same route of administration was used for species or strains that are compared. The degree of selectivity is expressed... 

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