Routes of exposure

Ibtal body accumulation reflects both total intake and the rate of elimination. Factors important in the rate of elimination include pharmacokinetics, lipid solubility, metabolism of the parent compound, profile of metabolites formed, rate of formation of reactive intermediates, degree of enzyme induction, amount of relevant covalent binding with subceUular macromolecules, and the rate of removal from the cell 

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The toxicity of common acryhc monomers has been characterized in animal studies using a variety of exposure routes. Toxicity varies with level, frequency, duration, and route of exposure. The simple higher esters of acryhc acid are usually less absorbed and less toxic than lower esters. In general, acrylates are more toxic than methacrylates. Data appear in Table 5. 

Hydraziae is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydraziae irritates the skin, eyes, and respiratory tract. Liquid splashed iato the eyes may cause permanent damage to the cornea. At high doses it can cause convulsions, but even low doses may result ia ceatral aervous system depressioa. Death from acute exposure results from coavulsioas, respiratory arrest, and cardiovascular coUapse. Repeated exposure may affect the lungs, Hver, and kidneys. Of the hydraziae derivatives studied, 1,1-dimethylhydrazine (UDMH) appears to be the least hepatotoxic monomethyl-hydrazine (MMH) seems to be more toxic to the kidneys. Evidence is limited as to the effect of hydraziae oa reproductioa and/or development however, animal studies demonstrate that only doses that produce toxicity ia pregaant rats result ia embryotoxicity (164). 

Human and animal studies indicate that inorganic manganese compounds have a very low acute toxicity by any route of exposure. The toxicity values for a given Mn compound are shown in Table 20 to depend on the species of test animal as well as the route of exposure. Manganese concentrations as high as 2000 ppm were found to be tolerated by test animals over a six-month period without any ill effects (208). 

Compound CAS Registry Number Test animal Route of exposure LD50 mg/kg... 

Acute Toxicity. Plasticizers possess an extremely low order of acute toxicity LD q values are mostiy in excess of 20,000 mg/kg body weight for oral, dermal, or intraperitoneal routes of exposure. In addition to thek low acute toxicity, many years of practical use coupled with animal tests show that plasticizers do not kritate the skin or mucous membranes and do not cause sensitization. 

Poly(ethylene oxide) resins are safely used in numerous pharmaceutical and personal-care appHcations. Poly(ethylene oxide) resins show a low order toxicity in animal studies by all routes of exposure. Because of their high molecular weight, they are poorly adsorbed from the gastrointestinal tract and completely... 

Depending on the circumstances of exposure, any given material may produce more than one type of toxic effect. Therefore, when describing toxicity for a particular material, it is necessary to define whether the effect is local, systemic, or mixed the nature of the injury the organs and tissues affected and the conditions of exposure, including route of exposure, number of exposures, and magnitude of exposure. 

Route of Exposure. As discussed below, the route of uptake may have a significant influence on the metaboHsm and distribution of a material. Differences in route of exposure may influence the amount of material absorbed and its subsequent fate. These differences may be reflected in variation in the nature and magnitude of the toxic effect. 

In order to induce a toxic effect, local or systemic, the causative material must first come into contact with an exposed body surface these are the routes of exposure. In normal circumstances, and depending on the nature of the material, the practical routes of exposure are by swallowing, inhalation, and skin and eye contact. In addition, and for therapeutic purposes, it may be necessary to consider intramuscular, intravenous, and subcutaneous injections as routes of adininistration. 

Skin. The skin may become contaminated accidentally or, in some cases, materials may be deHberately appHed. Skin is a principal route of exposure in the industrial environment. Local effects that are produced include acute or chronic inflammation, allergic reactions, and neoplasia. The skin may also act as a significant route for the absorption of systemicaHy toxic materials. Eactors influencing the amount of material absorbed include the site of contamination, integrity of the skin, temperature, formulation of the material, and physicochemical characteristics, including charge, molecular weight, and hydrophilic and lipophilic characteristics. Determinants of percutaneous absorption and toxicity have been reviewed (32—35,42,43,46—49). 

It is clear from the above considerations that the absorbed dose, and the distribution, excretion, and relative amounts of the absorbed material and its metabohtes may be quantitatively different for acute and repeated exposures. This modifies the potential for the absorbed material to produce adverse effects by a given route of exposure. 

Types of Studies. Studies may be conducted in five specimens (in vivo) or in test tubes in vitro). Studies may be carried out by single exposure or by repeated exposure over variable periods of time. The design of any one study, including the monitoring procedures, is determined by a large number of factors, including the nature of the test material, route of exposure, known or suspected toxicity, practical use of the material, and the reason for conducting the study. 

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. 

Human incidents have been reported in workers involved in the production or uses of PCNs. In the United States as well as in Germany and Austraha, the severity of the PCN-induced toxicosis was higher after exposure to the higher chlorinated PCN mixtures. In humans the inhalation of hot vapors was the most important route of exposure and resulted in symptoms including rashes or chloracne, jaundice, weight loss, yellow atrophy of the hver, and in extreme cases, death (75,77—79). 

Swallowing ethylene oxide is a highly unlikely route of exposure. However, harmful effects, including coma, death, and severe irritation and ulceration of the mouth and throat, could occur. 

Toxic hazards may be caused by chemical means, radiation, and noise. Routes of exposure are (1) eye contact, (2) inhalation, (3) ingestion, (4) skin contact, and (5) ears (noise). An Industrial Hygiene Guide (IHG) is based on exposures for an 8-h day, 40-h week, and is not to be used as a guide in the control of health hazards. It is not to be used as a fine hne between safe and dangerous conditions. 

Does the SAHP deseribe the prineipal ehemieal eontaminants, aflfeeted media, antieipated or measured eoneentrations, potential routes of exposure, and health effeets assoeiated with exposure to the eontaminants ... 

Another difficulty comes from the consideration of the route of entry (sf the contaminant, as chemicals can enter the body by various routes and the human body responds to the action of a toxic agent primarily on the basis of the rate and route of exposure. Without any doubt, the most important route of exposure at the workplace is inhalation, and this should be the route used to set OELs. However, if there is a threat of significant exposure by other routes, such as cutaneously (including mucous membranes and the eyes), either by contact with vapors or by direct skin contact w ith the substance, additional recommendations may be necessary. 

E.xposure assessment is tire detennination of tire magnitude, frequency, duration, and routes of exposure to human populations and ecosystems. 

The Material Safety Data Sheet (MSDS) is a detailed information bulletin prepared by the manufacturer or importer of a chemical tliat describes tlie physical and healtli hazards, routes of exposure, precautions for safe handling and use, emergency and first-aid procedures, and control measures. Infonnation on an MSDS aids in tlie selection of safe products and helps prepare employers and employees to respond effectively to daily exposure situations as well as to emergency situations. It is also a source of information for identifying chemical hazards. 

In both cases, tributyltin is included in the table for routes of exposure resulting from contamination of commercial dibutyltin direct exposure from the deliberate use of tributyltin is covered in the appropriate CIC AD (IPCS, 1999b). 

Chapter 3 Health Effects Specific health effects of a given hazardous compound are reported by type of health (death, systemic, immunologic, reproductive), by route of exposure, and by length of exposure (acute, intermediate, and chronic). In addition, both human and animal studies are reported in this section. 

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