Brain and fats

Following a 10-minute inhalation exposure to 2,000 ppm of benzene by pregnant mice, benzene and its metabolites were found to be present in lipid-rich tissues, such as brain and fat, and in well-perfused tissues, such as liver and kidney. Benzene was also found in the placenta and fetuses immediately following inhalation of benzene (Ghantous and Danielsson 1986). During inhalation exposure of rats to 500 ppm, benzene levels reached a steady-state concentration within 4 hours in blood (11.5 pg/mL),... 

I The apparent volume of distribution (Vd=Q/Cp) tells ns abont the characteristics of a drug (Vd=volume of distribution Q=quantity of drug Cp= plasma concentration). When Vd is high it indicates that the drug has a high affinity for tissues outside body water such as brain and fat. 

Long-chain and branched hydrocarbons that are primary components of JP-8, include -nonanc, -dccanc, -dodccanc, -tridecane, isopropylbenzene, -propylbcnzcnc, trirnethylbenzene, -dimcthylbenzene, naphthalene, n-pentylbenzene, and -tricthylbcnzcnc. Inhaled long-chain aliphatic hydrocarbons generally show poor blood uptake because of lower blood solubility. They have relatively high lipid blood partition coefficients this can result in accumulation in lipid-rich tissues, such as brain and fat. In laboratory studies, brain concentrations of hydrocarbons and their metabolites greatly exceed their plasma concentrations. 

Zahlsen et al. (1993) found that C8-C10 hydrocarbons were extremely well absorbed and their tissue distribution in brain and fat were largely dependent on the number of carbon atoms. -Nonane is one component of JP-8 and it is metabolized at relatively high rates to hydroxyl derivatives, which are converted to the corresponding ketone. Other important hydrocarbons (from a... 

Dixon et al. (2001) described a preliminary PB-PK model to predict JP-8 concentrations in Air Force fuel-cell maintenance workers. The model used data from PB-PK models of naphthalene inhalation in mice and rats and nonane inhalation in rats. In addition to inhalation, a pathway of dermal exposure and a skin compartment were included. For highly exposed people, the PB-PK model was generally in agreement with exhaled-air naphthalene concentrations however, predictions for the low-exposure scenarios were grossly underestimated, especially in female workers, by a factor of 10. The model did not predict blood and urinary concentrations. The major limitation of the Dixon et al. (2001) study was the lack of appropriate human data (e.g., metabolic measures, blood and tissue partition coefficients, and diffusion rates). The Dixon et al. (2001) model predicted a rapid decline in naphthalene concentrations in all compartments after exposure except liver, fat, and brain. The model predicted accumulation in liver, brain, and fat tissues for a 7-day period that included 4-hr exposures on 5 days. Competition for enzyme does not occur only from interactions of different inhaled compounds. Interactions can also occur between inhaled compounds and metabolites formed in the body that require similar enzymes for biotransformation. Detailed kinetic studies with both benzene and -hexane show inhibition of later metabolic steps, phenol to hydroquinone or methyl -butyl ketone to 2,5-hexane dione, by high concentrations of inhaled benzene or hexane, respectively (Medinsky et al. 1989 Andersen and Clewell 1984). 

Fnrthermore, the greater the lipid solubility of an anesthetic, the lower the anesthetic tension needed to produce anesthesia. At equilibrium, the concentrations of an anesthetic in the brain and fat cells are high, but are low in the blood. Finally, the potency of an anesthetic is inversely related to its minimum anesthetic concentration. 

Interesting facts. When using fire, the ancient man has discovered preservative properties of smoke. For tanning hides Indians applied a mixture of chopped liver, brain and fat. After currying the leather was smoked. Clothes from such leather were not hardened under the effect of water and microbes and its odor repelled mosquitoes. Another tanning method also existed. Leather was wrapped around the leg, then wrapped by foot wraps and carried until it gained best properties or leather was soaked in urine or dug in sheep manure. 

Fat has low blood flow. For example, five times more blood flows to the skin than to fat reserves (table 6.1). However, many chemicals are stored primarily in fatty tissues because they are lipophilic (fat-loving). For example, the distribution of DDT administered to laboratory rabbits through the diet was examined by chemically analyzing the organs. The results of this study indicated that roughly similar DDT concentrations were found in the brain and fat tissues, even though the brain receives 55 times higher blood flow than fat (table 6.1). 

Uniformly labeled C-8-D with a specific activity of 2.99 juc/mg was administered orally to pregnant females at 2 /xg/kg/day from 6-15 days of gestation. Three females were sacrificed on alternate days during days 6-20 of pregnancy. Triplicate samples of fetus, placenta, blood, brain, abdominal fat, and sartorius muscle were procured from each female. The samples were dissolved in 1 ml of Soluene (Packard Instruments) to which 15 ml of Aquasol were added. Each sample vial was counted for 30 min in a Nuclear Chicago Mark I liquid scintillation counter. 

Following oral administration of a lethal dose to a dog (25 mg. per kg. wettable powder) tissues taken immediately after death analyzed as follows no parathion recovered from bladder bile, liver, kidney, abdominal fat, saliva, or intestine small quantities (2 to 7 p.p.m.) of parathion recovered from oxalated blood, spleen, lung, brain, and spinal cord. The urinary bladder was strongly contracted and no urine could be collected. The results of these two experiments indicate a universal distribution of parathion following acutely lethal doses. 

Mineral oil may accumulate to some degree in liver and fatty tissues after absorption of ingested mineral oil hydraulic fluids, as indicated by experiments with rats given single, 0.66-mL, oral doses of tritiated mineral oil (Ebert et al. 1966). Twenty-four hours after administration, the concentrations of tritiated mineral oil in liver and fat were approximately seven-fold greater than those in kidney and brain other tissues were not examined. 

TRPV4 was identified a decade ago as an osmotransducer that is expressed in lung, heart, kidney, airway muscle cells, sensory neurons, brain, skin, gut, sympathetic nerves, inner ear, endothelium, and fat tissue [58-61]. TRPV4 is activated by heat (27-34°C), endogenous substances such as anandamide (59, AA) and the arachi-donic acid metabolite 5,6-epoxyeicosatrienoic acid (60, 5,6-EET), a plant dimeric diterpenoid bisandrographolide A (61, BAA), and the semisynthetic phorbol ester 4a-phorbol-12,13-didecanoate (62, 4a-PDD) [62],... 

In individuals who took thyroid hormones, 80% of the weight lost was lean body mass (muscle and bone) rather than excess fat. People taking these extracts experienced muscle weakness and bone breakdown, which led to a condition called osteoporosis, in which bones are weakened and the risk of bone fractures or breaks is increased. Thyroid hormone extracts also made the heart work harder by increasing metabolism, which led to problems such as increased heart rate, palpitations, and irregular heartbeat. These problems were potentially life threatening When the heart beats abnormally (or not at all), it is unable to pump blood and oxygen to the brain and body. Individuals die suddenly from this condition because the brain can only function for a few minutes without oxygen and nutrients. 

Residues were highest in abdominal and subcutaneous fat (235 mg/kg FW), followed by heart and spleen (75-91 mg/kg), then liver, brain, and blood (25-44 mg/kg) (Nomeirand Hajjar 1987)... 

Single oral dose of 30 pg 2,3,7,8-TCDD/kg BW to seawater-adapted juveniles Highest TCDD accumulations in visceral and extravisceral fat deposits. But Atlantic cod, Gadus morhua, treated similarly, accumulated TCDDs in liver and brain and to a significantly greater extent than did seawater-adapted rainbows 32... 

Single injection of radiolabeled famphur equivalent to 22.3 mg famphur/kg BW. Sheep killed at 96 h and tissues analyzed for residual radioactivity More than 50% of the administered dose was excreted within 6 h and 98% within 48 h. About 97% was excreted in urine and <3% in feces. Residues, in mg/kg FW, were 1.4 in blood 0.3-0.6 in kidney, liver, spleen, lung, and cerebrospinal fluid and <0.1 in bile, fat, brain, and muscle 7, 8... 

Mirex residues in 20 great homed owls (Bubo virginianus) found dead or dying in New York state in 1980 to 1982 contained concentrations of mirex and PCBs higher than those reported for great homed owls elsewhere (Stone and Okoniewski 1983). Owls in poor flesh contained higher residues than those in good flesh these values were 6.3 mg/kg FW vs. 0.07 mg/kg FW for brain, and 5.6 mg/kg FW vs. 0.1 mg/kg FW for liver (Stone and Okoniewski 1983). Waterfowl collected from upstate New York between 1979 and 1982 had about 0.07 mg mirex/kg FW breast muscle and 0.28 mg/kg FW subcutaneous fat (Kim et al. 1984, 1985). 

After a single oral dose, 0.44% remained after 9 days 82% of total residue was in kidney and liver, and lowest residues were in brain, spleen, and fat. A maximum residue of 45 mg/L was attained in blood plasma the Tb 1/2 in plasma was 13-121 h (USEPA 1980)... 

Partition coefficients of a series of aliphatic hydrocarbons, including n-hexane, have been determined in human tissues (Perbellini et al. 1985). The following partition coefficients for n-hexane (olive oil/air, blood/air, tissue/air) were determined olive oil, 146 blood, 0.80 liver, 5.2 kidney, 3 brain, 5 fat, 104 muscle, 5 heart, 2.8 and lung, 1. Saline/air partition was not reported separately for n-hexane, but was very low for the range reported for the entire group of compounds (0.1-0.4). 

The toxicokinetics of disulfoton in humans and animals depends on its physicochemical characteristics and its metabolism. The lipophilicity of disulfoton indicates that the insecticide should be easily absorbed by oral, inhalation, and dermal routes. No bioavailability data were located for inhalation and dermal exposure. However, disulfoton is almost completely absorbed from the gastrointestinal tract within 2 days after oral exposure. Animal studies suggest that disulfoton is widely distributed primarily to the liver and in smaller quantities to the kidney, fat, skin, muscle, brain, and other organs. Disulfoton and/or its metabolites are excreted mainly in the urine of humans and animals, with minor amounts excreted in the feces and expired air. 

Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils, [nih]... 

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