Toxic Effects of Laboratory Chemicals

C.3 Assessing Risks Due to the Toxic Effects of Laboratory Chemicals 41... 

In mammals, the toxicity of nickel is a function of the chemical form of nickel, dose, and route of exposure. Exposure to nickel by inhalation, injection, or cutaneous contact is more significant than oral exposure. Toxic effects of nickel to humans and laboratory mammals are documented for respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal, ocular, immunological, developmental, neurological, and reproductive systems (NAS 1975 Nielsen 1977 USEPA 1980, 1986 WHO 1991 USPHS 1993). 

In a second experiment (Hanhijarvi, Nevalainen, and Mannisto, 1985), the chronic, cumulative dermal effects of anthralin chemicals were studied in minipigs. Using only 12 animals, they were able, by having 32 sites per animal, to study the effects of two different chemicals (dithranol and butantrone both anthralins) in three different formulations at three different concentrations each. The protocol also included observations for systemic toxicity, clinical laboratory measurements, plasma drug analyses, and gross and histopathological examinations. 

In addition to the standard laboratory protection, such as safety goggles and chemically resistant butyl rubber gloves, a personal HF gas monitor with audible alarm and a safety sensor for liquids, as described in Section 10.4, are commercially available [2], For detailed information about the toxic effects of HF, see references Fi5, Wa8 and Re4. 

Because information on possible long-term effects of the other irritant chemicals used in the Edgewood tests is sparse, this chapter focuses on the effects of mustard gas and two lacrimators, CS and CN. Information on the potential long-term adverse effects of these chemicals is derived from several sources first, observation of long-term disabilities in soldiers who were exposed to a single (in most cases) toxic concentration of irritant during World War I and in persons exposed in peacetime accidents or riot-control procedures second, studies of morbidity in workers chronically exposed to chemical irritants during their manufacture and third, studies in which experimental laboratory animals were exposed to selected chemicals by topical application, injection, or aerosol inhalation. 

In most cases, limited information is available regarding the toxic effects of chemicals. Empirical guidelines are then used in an attempt to protect most of the aquatic ecosystem s biota. The regulation of chemicals, for instance, generally uses safety factors from 10 to 1000 depending on the number of species tested. Mesocosm studies or comparisons with real field situations are accepted with lower safety factors on a case by case basis, since these studies reduce the uncertainty linked to the relevance of laboratory models in terms of site-specific data. 

Determination of exposure and toxic effects of chemicals also requires knowledge of toxicokinetics. Toxicokinetics is the study of changes in the levels of toxic chemicals and their metabolites over time in various fluids, tissues, and excreta of the body, and determines mathematical relationships to explain these processes. These processes depend upon uptake rates and doses, metabolism, excretion, internal transport, and tissue distribution. Methods for determining these processes include studies with laboratory animals, volunteer human subjects, persons accidentally exposed to high doses of chemicals, and experiments with tissue or organs cultured in the laboratory. Computer simulations of such processes are often formulated using complex mathematical equations. 

The toxic effects of some pesticide mixtures are additive, particularly when their toxic mechanisms are identical. The additive effects of the organophosphates chlorpyrifos and diazanon were demonstrated in one study. T Another study found the s-triazine herbicides atrazine and cyanazine to show additive toxic effects. Not all mixtures of similar pesticides produce additive effects, however. In one study, mixtures of five organophos-phate pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion) were shown to produce greater than additive effects when administered to laboratory animals. Another article discusses nonsimple additive effects of pyrethroid mixtures. Despite the similarities in their chemical structure, pyrethroids act on multiple sites, and mixtures of these produce different toxic effects. 10 ... 

Numerous studies have been carried out on the effects of single chemicals on the liver, of which ethanol and carbon tetrachloride are the most notorious. [4,81 Other hepatotoxic chemicals, however, have also been widely studied, both in the laboratory and environmentally. For example, an outbreak of toxic liver disease was reported in a fabric coating company. Upon investigation, it was found that dimethylformamide, a known hepatotoxin, was used as a coating solvent in poorly ventilated areas without appropriate skin protection, and no other hepatotoxins were identified. 1121... 

The task of assessing the effect of a chemical substance on the environment is complicated by the complexity of living organisms that may be affected by the chemical substance. To consider toxic effects, a reference species is used. It should be understood that the experiments done are models in a laboratory to understand effects in the outside world at the ecological level. The real challenge is to study the effects produced out in the environment. So a simplified model of real-world phenomena must be also used. The few selected species must represent all the various other species. Because it is not possible... 

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