Subject toxic effects

Sublethal doses of most toxic substances are eventually eliminated from an organism s system. If there is no lasting effect from the exposure, it is said to be reversible. However, if the effect is permanent, it is termed irreversible. Irreversible effects of exposure remain after the toxic substance is eliminated from the organism. Figure 6.7 illustrates these two kinds of effects. For various chemicals and different subjects, toxic effects may range from the totally reversible to the totally irreversible. 

For carckiogen pesticides (70,71), animal testkigs are subject to maximum tolerated doses (M I L)). M I D is the maximum amount of a substance that can be administered to an experimental animal without causkig extreme health consequences, such as death, to occur but while continuing to produce some measurable toxic effects. Current regulatory theory holds that carckiogen effects do not have a threshold and caimot be related to reference doses. 

Some authorities question whether dmnkeimess can result from the inhalation of ethyl alcohol vapors. Experience has demonstrated that in any event such intoxication is indeed rare (281). There is no concrete evidence that the inhalation of ethyl alcohol vapor will cause cirrhosis. Liver function is definitely impaired during alcohol intoxication (282), making the subject more susceptible to the toxic effects of chlorinated hydrocarbons. 

This volume does not address subjects such as toxic effects, explosions in buildings and vessels, runaway reactions, condensed-phase explosions, pool fires, jet flames, or structural responses of buildings. Furthermore, no attempt is made to cover the frequency or likelihood that a related accident scenario will occur. References to other works are provided for readers interested in these phenomena. 

A slight toxic effect ( toxic defined as negative effects on health, growth, and reproduction) of the treated receiving water on the green alga Spiropyra species as a typical representative of the P-mesosaprobic zone was observed, when the test unit was subjected to the impact of 40 ppm secondary alkanesulfonates. 

The primary objective of a Phase I trial is to assess the safety of the drug in humans. Studies are normally conducted in healthy male volunteers, although specific categories of subject may be used in certain cases. For example, to avoid the risk of low blood pressure, subjects with mild hypertension would be more appropriate for the evaluation of antihypertensive drugs, while patients are likely to be used in the case of drugs that are expected to produce significant toxic effects (e.g. anti-cancer cytotoxic drugs). Remuneration may be offered for participation in the study. The number of subjects is normally between 10 and 100 people. 

Extraction procedures must be adjusted when separated anthocyanins will be tested in biological studies. We have found that the types of acids used for anthocyanin extraction as well as their residual concentrations in the final extract may affect the results obtained from biological tests. The growth inhibitory effect of anthocyanins on HT29 (human colonic cancer) cells may be overestimated if the residual acid in the extract exerts a toxic effect on the cells. Acetic acid residues in anthocyanin extracts showed less toxicity to HT29 cells than hydrochloric acid when samples were prepared under the same extraction procedure and subjected to the same tests on HT29 cells. In addition, the procedure to remove acids affected the acid residual concentration as well in final anthocyanin extracts, with lyophilization being more successful than rotary evaporation. 

A case report of acute arsine poisoning in which a 27-y-old man was exposed to arsine during chemical manufacturing was reported by Pinto (1976). The subject was exposed to arsine as a result of arsine production via a reaction between a galvanized bucket and an arsenic-containing sulfuric acid solution. The exposure (duration not specified) produced toxic effects characterized by abdominal cramping, thoracic discomfort, and hematuria. Over the next week, the patient s hematocrit declined from 42.5 to 27.1 and hemoglobin dropped from 14.1 to 9.5 g/dL even with medical intervention (blood transfusions and mannitol diuresis). Nine hours after exposure, blood arsenic was 159 g/dL and urinary arsenic was 1862 ug/L. 

Since food additives are subjected to the most stringent toxicological testing procedures, only a few synthetic antioxidants have been used in foods for any length of time. Antioxidants are extensively tested for the absence of carcinogenity and other toxic effects in themselves, in their oxidised forms, and in their reaction products with food constituents, for their effectiveness at low concentrations, and for the absence of the ability to impart an unpleasant flavour to the food in which they are used. 

Interest in nitroso compounds as intermediates for organic synthesis has faded due mainly to their potential toxic effects. Table 6, shows that activity in this field is centered mainly on occupational and environmental pollution subjects. An ample review appeared recently on V-nitroso compounds, including chemical, biochemical and analytical aspects566. 

We are coming close to the central topic of toxicity, which obviously cannot occur until chemicals actually contact various parts of the body. But there is one more exceedingly important step that needs to be examined before toxic effects are considered. How do chemicals enter, move around within, and exit the body With this subject we begin to understand the relationship between the doses the body experiences from contact with environmental media to those doses that come to be present in different fluids, organs, and cells of the body. 

For all toxic effects other than carcinogenicity, a threshold in the dose-response curve is assumed. The lowest NOAEL from all available studies is assumed to be the approximate threshold for the groups of subjects (humans or animals) in which toxicity data were collected. Alternatively, a benchmark dose (BMD) may be estimated from the observed dose-response curve, and used as the point-of-departure for risk assessment (see below and Box). 

Chronic-Duration Exposure and Cancer. No studies were located regarding chronic inhalation exposure to 1,2-diphenylhydrazine in humans or animals. As discussed for acute-and intermediate-duration exposure, 1,2-diphenylhydrazine is a solid With a low vapor pressure at ambient temperature, which makes inhalation exposure this chemical in the vapor state unlikely. However, the possibility of inhalation exposure to dusts of 1,2-diphenylhydrazine either free or adsorbed to soil is conceivable. Therefore, chronic-duration studies of inhalation exposure to dusts of 1,2-diphenylhydrazine could be designed to provide information on possible toxic effects and exposure levels that cause effects. The NCI (1978) bioassay of 1,2-diphenylhydrazine provides the only sufficient chronic oral toxicity data for this chemical. This study was not, however, subjected to the peer review process used for current NTP bioassays, and it inadequately evaluated nonneoplastic effects. Additional studies would be particularly useful for corroborating and more fully characterizing... 

The chemical or physical form of trace metals in water is often of interest. The form in which a specific element is present will often influence is toxic effects. For instance the chemical state of chromium affects its toxicity i.e., Cr+6 is more carcino genic than Cr+3, Kopp (48) has described the various forms in which metals may he present. The categories include dissolved metals, suspended metals, total metals, extractable metals and organometallics. In addition, Kopp describes sample preparation requirements for each category. Gihhs (20) has also studied metal species in river water. It should be obvious that the desired analytical result has to he considered beforehand. For example, if dissolved metal concentrations were desired and normal acid preservation performed, suspended metals could possibly be solubilized to a large extent. Both Hamilton (25) and Robertson (81) have shown vast differences between acidified and non-acidified samples. Many other publications have dealt with this subject (16, 37, 80, 30). 

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