Human route

The route and duration of administration of the agent is also critical for the development of the teratogenic anomaly. Human industrial exposure is almost always by inhalation or percutaneous absorption of fumes, aerosols or vapors. Consumer or other secondary exposure would be by more varied routes. Experimental teratology endeavors to duplicate the human route of exposure for experimental animal models. Inhalation presents problems of... 

Of these three options, a properly conducted long-term chronic bioassay has been accepted as the definitive model for estimating the carcinogenic risk for humans. Having mammalian tumor-induction as its end-point, the chronic bioassay is the only source of direct evidence (other than in humans) of chemically induced tumors in the mammalian species. Of all test systems it comes the closest to mimicking human routes of exposure and metabolic/pharmacological processes which activate and distribute chemicals. 

The extent of absorption of an administered dose of silver depends on silver speciation, the presence and extent of silver-binding proteins, and other variables. But absorption is dependent mainly on the transit time through the gastrointestinal tract the faster the transit time, the less silver is absorbed. Transit times ranged from about 8 h in mice and rats to about 24 h in monkeys, dogs, and humans. Route of administration affected the excretion rate of silver. Clearance of silver from mammals 2 days after silver was admmistered intravenously ranged... 

The first line gen (route section) tells the system that we want to define our own function. The lines 2, 3, and 4 are a blank line, program label (for human readers), and a blank line. The next line that is read by the system is 0 2, specifying that the ground state of H has a 0 charge and is a spin doublet (one unpaired election). The next line, h, specifies hydrogen, followed by a blank. 

The first line in File 9-1 is the route section calling for a PM.3 optimization. The next three lines are a blank line, a program label (human input not read by the system), and a blank line. The input (J I indicates that the charge on the molecule is 0 and the spin multiplicity is I (paired electrons). The starting geometry is given in... 

There are thousands of breweries worldwide. However, the number of companies using fermentation to produce therapeutic substances and/or fine chemicals number well over 150, and those that grow microorganisms for food and feed number nearly 100. Lists of representative fermentation products produced commercially and the corresponding companies are available (1). Numerous other companies practice fermentation in some small capacity because it is often the only route to synthesize biochemical intermediates, enzymes, and many fine chemicals used in minor quantities. The large volume of L-phenylalanine is mainly used in the manufacture of the artificial dipeptide sweetener known as aspartame [22389-47-0]. Prior to the early 1980s there was httle demand for L-phenyl alanine, most of which was obtained by extraction from human hair and other nonmicrobiological sources. 

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). 

Toluenediamine is classed as toxic. The oral LD q for animals is between 270—350 mg /kg body weight (45). TDA is readily absorbed through the skin and this is the major route of human exposure. Several studies have shown the 2,4 isomer of TDA to be carcinogenic for rats and mice, but tests on the 2,5 and 2,6 isomers were not positive. AH three of the isomers have been shown to be mutagenic (45). Results of limited studies on the reproductive ha2ards for male workers are equivocal, but animal experiments have shown TDA to cause adverse reproductive effects (45). 

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. 

In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

Value is toxic dose low. TD q, the lowest dose of a substance introduced by any route other than inhalation, over any given period of time to which humans or animals have been exposed and reported to produce any nonsignificant toxic effect in humans or to produce nonsignificant tiimorigenic or reproductive effects in animals or humans. 

Ethylene dibromide is a suspected human carcinogen and worker exposure by all routes should be carefiiUy controUed to levels as low as reasonably achievable (67). Ethylene dibromide causes severe blistering of the skin if contact is prolonged. Eye contact with the Hquid will cause pain, irritation, and temporary impairment of vision. Recommended safety equipment includes safety goggles, a NIOSH approved canister-type gas mask for organic vapors, neoprene gloves, and neoprene overshoes. In case of contact with ethylene dibromide, contaminated clothing and shoes should be removed and eyes or skin washed with plenty of water for at least 15 minutes. Contaminated clothes should be washed before reuse and contaminated shoes should be discarded. 

Human Health Effects. Any assessment of adverse human health effects from PCBs should consider the route(s) of and duration of exposure the composition of the commercial PCB products, ie, degree of chlorination and the levels of potentially toxic PCDF contaminants. As a result of these variables, it would not be surprising to observe significant differences in the effects of PCBs on different groups of occupationally-exposed workers. 

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). 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Carcinogenicity of DGEBPA or DGEBPA-based resins, as measured by topical appHcation, has not been shown by a majority of the studies (45). Advanced DGEBPA resins exhibit low systemic toxicity either by dermal or oral routes and inhalation of these resins is unlikely because of low volatihty. The acute oral LD q in rats has been reported to be >2000 mg/kg (46). Acute dermal studies show these materials have alow potential for absorption through the skin in acutely toxic amounts. No evidence of carcinogenicity has been found in animals or humans for advanced DGEBPA resins (47,48). 

Of all the uncertainties surrounding the hypothesis that environmental chemicals with endocrine disrupting properties are responsible for the observed effects in humans and wildlife, one of the major unknowns relates to exposure. Humans and wildlife can be, and sometimes are, exposed to these substances in the environment but our knowledge of the levels, routes and timing of exposure is poor. 

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