Toxicity human experience

Risk characterization is defined as the integration of the data and analysis of the above three components to determine the likelihood that humans wiU. experience any of the various forms of toxicity associated with a substance. When the exposure data are not available, hypothetical risk is characterized by the integration of hazard identification and dose—response evaluation data. 

Recently, some models have been derived to analyze the occurrence of interactive joint action in binary single-species toxicity experiments (Jonker 2003). Such detailed analysis models are well equipped to serve as null models for a precision analysis of experimental data, next to the generalized use of concentration addition and response addition as alternative null models. However, in our opinion these models are not applicable to quantitatively predict the combined toxicity of mixtures with a complexity that is prevalent in a contaminated environment, because the parameters of such models are typically not known. Recently a hazard index (Hertzberg and Teus-chler 2002) was developed for human risk assessment for exposure to multiple chemicals. Based on a weight-of-evidence approach, this index can be equipped with an option to adjust the index value for possible interactions between toxicants. It seems plausible that a comparable kind of technique could be applied in ecotoxicological risk assessments of mixtures for single species. However, at present, the widespread application of this approach is prevented by lack of available information. 

Exposure to toxic fire effluents can lead to a combination of physiological and behavioral effects of which physical incapacitation, loss of motor coordination, disorientation are only a few. Furthermore, survivors of a fire may experience postexposure effects, complications, and burn injuries, leading to death or long-term impairment. The major effects, such as incapacitation or death, may be predicted using existing rat lethality data, as described in ISO 1334431 or more recently, based on the best available estimates of human toxicity thresholds as described in ISO 13571,5 by quantifying the fire effluents in different fire conditions in small-scale tests, using only chemical analysis, without animal exposure. 

The study of human populations is called epidemiology, and it is used to determine the agents that cause disease, including chemicals such as drugs and industrial and environmental chemicals. The potential toxicity of industrial chemicals has to be evaluated in vitro and in animals, but the long-term exposure that humans may experience cannot always be simulated in these experiments. Thus epidemiology is an essential tool. 

Adaptation to CO toxicity also seems to occur in humans. Doing experiments on herself, KiUick (1940) found diminished symptoms and lower COHb on chronic exposure to CO than in the beginning, which is in accord with the data of Haldane and Priestley (1935). Adaptation to hypoxia is the reason why people living at high altitudes feel perfectly normal while a visitor Irom the plains may feel quite unwell. Indian and Pakistani soldiers are facing one another in Siachen of Kashmir, the highest place for any military confrontation in the world. Unless the soldiers are acch-matized before they go to Siachen, many develop fatal pulmonary edema if they are acclimatized, the incidence of pulmonary toxicity is considerably reduced. 

Thus it is feasible that a specific profile of toxicity is seen to occur in repeat-dose animal studies at a dose/concentration below the guidance value, eg. <100 mg/kg bw/day by the oral route, however the nature of the effect, e.g. nephrotoxicity seen only in male rats of a particular strain known to be susceptible to this effect, may result in the decision not to classify. Conversely, a specific profile of toxicity may be seen in animal studies occurring at above a guidance value, eg. at or above 100 mg/kg bw/day by the oral route, and in addition there is supplementary information from other sources, e.g. other long-term administration studies, or human case experience, which supports a conclusion that, in view of the weight of evidence, classification would be the prudent action to take. 

Human toxic effects not predicted from animal experiments are often reversible, but even the most optimistic enthusiasts for drugs must shrink from the thought that their hands wrote prescriptions resulting in deformed, surviving babies. 

Ototoxicity can occur when benzalkonium chloride is applied to the ear and prolonged contact with the skin can occasionally cause irritation and hypersensitivity. Benzalkonium chloride is also known to cause bronchoconstriction in some asthmatics when used in nebulizer solutions. Toxicity experiments with rabbits have shown benzalkonium chloride to be harmful to the eye in concentrations higher than that normally used as a preservative. However, the human eye appears to be less affected than the rabbit eye and many ophthalmic products have been formulated with benzalkonium chloride 0.01% w/v as the preservative. 

Some herbicides are sprayed on the leaves and others are applied to the soil and are taken up by the roots (systemics). Some herbicides are growth promoters and kill the plant by causing it to grow too fast. Others function by closing the stomata and "suffocating" the plant. The triazine herbicides in this experiment appear to stop photosynthesis by reacting with the enzymes catalyase and peroxidase. The herbicides have very low human toxicity. 

If toxicity studies in animals or previous human exposure experience indicates that a product is or may be capable of producing any of these situations, that fact must be clearly stated on the label. At times such information may appear in the Warning Section of the label. Since that section may be located on another part of the label some distance from the first aid statement or that section may be obscured for a variety of reasons, it is prudent to repeat such information at the beginning of the first aid statements. 

Nickel, especially, is a metal with high human toxicity and has shown carcinogenicity in animal experiments. The problem of metal contamination of the final product is even more difficult as the metal might be incorporated inside the protein and is not easily removed by any subsequent purification step, for example, dialysis or ion exchange. 

It is difficult to compare these results with the literature. Nevertheless, there are some data dealing with i.v. toxicity of the VX (S18) in healthy volunteers, the value of i.v. LD50 was assessed to be 10 //g/kg or 7 /rg/kg (M2). It appears from our results that the calculated i.m. LD50 value was 20 /ig/kg. These data are in good agreement because the percentage of the i.v. dose is about 40 to 60%i of the i.m. dose (Bll). It can be concluded that this methodical approach at least allows us to assess the toxicity of some OP to humans without experiments on volunteers, which has been considerably hazardous for that particular group of substances. 

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