Excretion exposure

See also Biotransformation Distribution Excretion Exposure Gastrointestinai System Modifying Factors of Toxicity Pharmacokinetics/Toxicokinetics Respiratory Tract Skin Toxicity Testing, Dermai Toxicity Testing, Inhaiation. 

Rats exposed to 500 ppm of bromotrifluoroethylene died following a 4-h exposure. Since the monomer decomposes in air, the level of exposure to it was actually lower. The effects in rats of repeated exposure over a two-week period have been studied. At 50 ppm, the animals lost weight and renal damage was noted although the effect was reversible. Very mild testicular damage was seen at 50 but not 10 ppm. The amount of urinary duotide excreted suggested that extensive metaboHsm was occurring (34). 

Lead enters the body through inhalation and ingestion, is absorbed into the circulatory system from the lungs and digestive tract, and excreted via the urine and feces. Normally, intake of lead approximately equals output. However, excessive exposure and intake can cause tissue concentrations to increase to the point where illness can result. 

The dermal adsorption of DEBT in humans has been studied in the Netherlands by appHcation of DEBT as undiluted technical material or as 15% solutions in alcohol. Labeled material was recovered from the skin, and absorption of DEBT was indicated by the appearance of label in urine after two hours of skin exposure. About 5—8% of the appHed treatments was recovered as metaboHtes from urine, and excretion of metaboHtes in the urine came to an end four hours after exposure ended. DEBT did not accumulate in the skin, and only a small (less than 0.08%) amount ended up in feces. Curiously, less has been absorbed through skin from 100% DEBT appHcation (3—8%, mean of 5.6%) than from 15% alcohol appHcation (4—14%, mean of 8.4%). These results have been described as consistent with previous absorption/metaboHsm studies using guinea pigs, rats, and hairless dogs. Other pubHcations on DEBT toxicology have been cited (92). 

Tb allium, which does not occur naturaHy in normal tissue, is not essential to mammals but does accumulate in the human body. Levels as low as 0.5 mg/100 g of tissue suggest thallium intoxication. Based on industrial experience, 0.10 mg /m of thallium in air is considered safe for a 40-h work week (37). The lethal dose for humans is not definitely known, but 1 g of absorbed thallium is considered sufficient to kHl an adult and 10 mg/kg body weight has been fatal to children. In severe cases of poisoning, death does not occur earlier than 8—10 d but most frequently in 10—12 d. Tb allium excretion is slow and prolonged. For example, tb allium is present in the feces 35 d after exposure and persists in the urine for up to three months. 

The kidney is an important organ for the excretion of toxic materials and their metaboHtes, and measurement of these substances in urine may provide a convenient basis for monitoring the exposure of an individual to the parent compound in his or her immediate environment. The Hver has as one of its functions the metaboHsm of foreign compounds some pathways result in detoxification and others in metaboHc activation. Also, the Hver may serve as a route of elimination of toxic materials by excretion in bile. In addition to the Hver (bile) and kidney (urine) as routes of excretion, the lung may act as a route of elimination for volatile compounds. The excretion of materials in sweat, hair, and nails is usually insignificant. 

It is important to appreciate that the magnitude of the absorbed dose, the relative amounts of bio transformation product, and the distribution and elimination of metaboUtes and parent compound seen with a single exposure, may be modified by repeated exposures. For example, repeated exposure may enhance mechanisms responsible for biotransformation of the absorbed material, and thus modify the relative proportions of the metaboUtes and parent molecule, and thus the retention pattern of these materials. Clearly, this could influence the likelihood for target organ toxicity. Additionally, and particularly when there is a slow excretion rate, repeated exposures may increase the possibiUty for progressive loading of tissues and body fluids, and hence the potential for cumulative toxicity. 

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. 

Exposure to tetrachloroethylene as a result of vapor inhalation is foUowed by absorption into the bloodstream. It is partly excreted unchanged by the lungs (17,18). Approximately 20% of the absorbed material is subsequently metabolized and eliminated through the kidneys (27—29). MetaboHc breakdown occurs by oxidation to trichloroacetic acid and oxaHc acid. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

Aquatic organisms, such as fish and invertebrates, can excrete compounds via passive diffusion across membranes into the surrounding medium and so have a much reduced need for specialised pathways for steroid excretion. It may be that this lack of selective pressure, together with prey-predator co-evolution, has resulted in restricted biotransformation ability within these animals and their associated predators. The resultant limitations in metabolic and excretory competence makes it more likely that they will bioacciimiilate EDs, and hence they may be at greater risk of adverse effects following exposure to such chemicals. 

TCDD is the most potent inducer of chloracne. This has been well known since the accident in Seveso, Italy, in 1976 in which large amounts of TCDD were distributed in the environment subsequent to an explosion in a factory that produced a chlorophenoxy herbicide, 2,4,5-T. TCDD is an impurity produced during the production of 2,4,5-T. The most common long-term effect of TCDD exposure was chloracne. Exposed individuals also suffered increased excretion of porphyrins, hyper-pigmentation, central nervous system effects, and liver damage and increased risk of cancer was a long-term consequence of the exposure. In addition to TCDD, polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans, and polychloronaphthalens cause chloracne as well as other effects typical of TCDD. 7i... 

In this scheme, OELs should be a dose somewhere between compensatory effects, in which the organism is able to detoxify, metabolize, or excrete the substance, and early impairment. Although there may be profound differences of opinion as to what constitutes this dose, this approach leads to the conclusion that available scientific data permits identification of a clear threshold dose below which exposure to the substance in question is not expected to lead to adverse effects. 

One of six workers died 12 days after exposure to a mixture of half dimethyltin dichloride and half trimeth-yltin chloride vapour during cleaning of a cauldron at a chemical plant in Germany in 1981. Maximum exposure time was 1.5 h over a 3-day period no estimates of exposure concentration were made. Symptoms preceding death included excretion of high levels of tin in the urine, respiratory depression, and coma (Rey et al.,... 

Often, absorption occurs by multiple routes in humans. Dean et al. (1984) reported deaths and toxic effects as well as lowered blood cholinesterase levels and excretion of urinary 4-nitrophenol in several children who were exposed by inhalation, oral, and possibly dermal routes after the spraying of methyl parathion in a house. In the same incident (Dean et al. 1984), absorption was indicated in adults who also excreted 4-nitrophenol in the urine, though at lower levels than some of the children, and in the absence of other evidence of methyl parathion exposure. In this study, the potential for age-related differences in absorption rates could not be assessed because exposure levels were not known and the children may have been more highly exposed than the adults. Health effects from multiple routes are discussed in detail in Section 3.2. 

Most of the toxic effects caused by methyl parathion resulted from exposure by multiple routes, especially for workers in sprayed fields or formulating facilities, or people in homes. Dean et al. (1984) reported deaths and toxic effects in several children as well as lowered blood cholinesterase levels and excretion of urinary 4-nitrophenol (adults showing no adverse effects also excreted 4-nitrophenol). 

No studies were located regarding excretion in animals after inhalation exposure to methyl parathion. 

Limited information was available regarding excretion in humans after oral exposure to methyl parathion. During 5 days of exposure of four subjects to 2 or 4 mg of methyl parathion once daily in food (0.028 or... 

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