Feasibility of metabolic parameter estimation in pharmacokinetic models of carbon tetrachloride exposure in rats1

Carbon tetrachloride (CCl₄) is a toxic chemical that was once used in degreasers and detergents, and some remnants of the chemical may be present in the water supply. Physiologically-based pharmacokinetic (PBPK) modeling can assist in understanding resulting internal doses of CCl₄ after exposure, but the pharmacokinetic parameters describing the metabolism of CCl₄ are not well characterized. The goal of this study was to provide insights into how to more accurately estimate these values in rats using PBPK modeling and data from previous studies. Three different PBPK models were constructed to describe CCl₄ exposure in rats via inhalation, oral ingestion, and venous injection. Each of these models was compared to data, and sensitivity analysis was performed for each model to determine whether the available data could be used to accurately determine the metabolic parameters of interest. These parameter sensitivities were so low that optimization to the available data yielded physiologically unrealistic results. Model sensitivities were analyzed for different doses and routes of exposure in order to find experimental conditions that would allow for greater identifiability of the metabolic parameters. Data were simulated from these models at optimal conditions with varying levels of noise from a normal distribution. Optimizations were then performed to confirm that the original values could be obtained. The experiments developed are left as suggestions for investigators who wish to further pursue estimating these metabolic parameters.     

Adsorption and movement of carbaryl in soils: A verification of cosolvent theory and comparison of batch equilibrium and soil thin layer chromatography results

Batch equilibrium and soil thin layer chromatography (TLC) techniques were used to investigate the influence of different volume fractions of organic cosolvents (acetone and methanol) on the adsorption and movement of carbaryl in four different types of Indian soils. L-shaped isotherms were obtained for both the cosolvent–water mixtures at all f _s values and were in close agreement with the Freundlich equation. Higher adsorption was observed on F.R.I. soil (FSL) followed by Alampur soil (ASL), Kalai soil (KL), and Bhoran soil (BSL) at all f _s values for both the cosolvent systems as was anticipated from the K and K _D values. The K and K _D values also confirmed that carbaryl adsorption was higher in methanol–water mixture than acetone–water mixture and decreased with increasing f _s values. The frontal R _f values obtained from soil TLC studies were inversely proportional to the K and K _D values for both the cosolvent systems. The higher K and K _D values and lower R _f values in methanol–water mixtures relative to acetone–water mixtures for all the soils indicated that acetone had a greater potential for ground water contamination compared to methanol. The adsorption data were used to evaluate the cosolvent theory for describing adsorption of carbaryl in acetone–water and methanol–water mixtures. The aqueous phase partition coefficients, K _DW (mol g^?1), normalized with respect to f _oc for carbaryl was evaluated by extrapolating f _s → 0.     

Biochemical assessment of lead,phenol, and benzene-contaminated water on the heart and blood of Albino rats

A study was performed to evaluate the effect of contaminated water on the tissues of Rattus novergicus (albino rats). Test rats were given water contaminated with lead (0.015 µg L^?1 tap water), phenol (0.05 mL L^?1 tap water), and benzene (0.05 mL L^?1 tap water), while control rats were given tap water over a period of 65 days after which the activity of selected enzymes of the heart and serum was assayed, and hematological parameters and serum lipid profiles were also determined. Generally, a significant (p < 0.05) drop in the activity of the enzymes was observed in the heart of test rats relative to the control rats. However, the serum activities increased significantly in the test group compared to the control group (p < 0.05). The concentrations of serum cholesterol, low-density lipoprotein (LDL), and triglycerides of the test rats were found to be significantly higher than those of the control rats (p < 0.05). Concentrations of hemoglobin, red blood cell count, and packed cell volume of test rats were observed to be significantly lower than those of the control rats (p < 0.05). The experimental results indicated that consumption of water contaminated with lead, phenol, and benzene may damage the heart, increase the risk of atherosclerosis as reflected by the serum lipid profile, and anemia as suggested by abnormal hematological properties.     

The status of heavy metal levels in a Ramsar site,Kuala Gula bird sanctuary: the impact of the anthropogenic inputs

Distributions of Cd, Cu, Pb, and Zn in the surface sediments from two sites of the Kuala Gula Bird Sanctuary, Malaysia were monitored for a period of 6 months from October 2006 to March 2007. In December 2006, the concentration of Zn in one location was significantly (p??1) than the other metals at both sites, but in the oxidizable organic fraction it was highest at both sites during October; with mean concentrations of 18?mg?kg^?1 at both locations. In the acid-reducible fraction, high concentrations of Pb (2.3?mg?kg^?1) were detected at station 2 in February 2007, being highest among all four metals at both stations. The acid-reducible fraction found in Pb ranged from 0.10% to 3.1% in both stations. Percentages ranging from 51% to 96% were observed for all four metals in the resistant fraction throughout the sampling period. These results indicate low contributions from anthropogenic sources. The findings constitute a baseline data archive for future reference.     

Effects of β-cyclodextrin on adsorption and desorption of carbofuran in soils of divergent texture

Laboratory studies were conducted to determine the adsorption/desorption equilibrium of carbofuran between four divergently textured soils and distilled water and an aqueous solution of 0.01?mol?L^?1 β-cyclodextrin using a batch equilibrium technique. The determined adsorption isotherms for silt loam soils were of L-shaped, for sandy loam soil S-shaped, in agreement with a Freundlich isotherm. In the presence of β-cyclodextrin, the adsorption of carbofuran to the four soils was lower than with distilled water. Positive hysteresis was observed in all soils with distilled water, negative hysteresis when using a solution of β-cyclodextrin as desorbent. The results indicate the potential use of β-cyclodextrin for remediation of pesticide-contaminated soils.     

Hazardous waste management in educational and research centers: a case study

The hazardous waste management (HWM) practice at Tehran University of Medical Sciences Central Campus, Iran, was investigated in this study. Four schools were selected and the required information such as type and amount of wastes, temporary storage methods, waste discharge frequency, and final waste disposal methods using sampling, questionnaires, interviews with laboratory staff, and reference to available documents were gathered. The quantity of hazardous waste generation per year excluding the uncontrolled wastewater was found to be 2.072 tons per year. The obtained results show that wastes having features of being infectious, toxic, ignitable, carcinogenic, corrosive, and reactive were present at 32%, 28%, 16%, 14%, 8%, and 2%, respectively. In the central campus, hazardous solid wastes managed with household solid wastes and hazardous liquid waste were discharged into the sinks without any kind of control; improper HWM practices are evident from the point of waste production to final disposal.     

Mercury exposure through diet in pregnant women and women of childbearing age

The study examined the stage of clean-up of the Port Lavaca bay sites in Texas, which were polluted during the early 1990's by effluent containing mercury (Hg) from a chloralkali plant. In addition to Hg intoxication through environmental contaminations, human exposure through dietary fish and other seafoods occurred. Bacteria converts inorganic Hg to alkyl organic compounds and subsequently the metal crosses the blood brain barrier thus exerting adverse effects on the fetal developing nervous system. In order to conduct a survey of dietary Hg exposure, blood was collected from pregnant women and those of childbearing age at routine clinic visits at each of three centers in South Texas cities (Galveston, Texas City, Port Lavaca/Victoria, TX). A questionnaire sought dietary and lifestyle information including consumption, sources of fish and other seafoods. A significant number of subjects (119 out of 175, 68%) ate fish caught locally. The blood Hg concentrations (µg?L^?1) range varied with the location of the study centers: City of Galveston 2.6–62; Texas City 2.8–111.8; and the Port Lavaca areas 3.02–126.7. The concentrations of blood Hg was directly proportional to the number of fish meals consumed for each species considered. Mean blood Hg concentrations for no fish meals per week were: Port Lavaca 4.5 (N?=?3), Galveston 4.3 (N?=?3), Texas City 3.5 (N?=?10). For >3 fish meals per week, the mean blood Hg concentrations were: Port Lavaca, 48.0 (N?=?53), Galveston 29.1 (N?=?35), Texas City, 36.1 (N?=?31). Data show that residues of Hg were still present in 1994 despite the clean-up efforts.     

Effects of benzo(a)pyrene on blood components,tumor markers,and oxidative status in mice

This study was carried out to investigate the effect of long-term exposure to benzo(a)pyrene (B(a)P) in mice. Hemogram, tumor markers, oxidative status, and B(a)P residues in liver tissue were evaluated. Sixty albino Swiss mice were randomly distributed equally into three groups; the control was given 0.1?mL corn oil once a week for 8 weeks. The other two groups were given 20 and 40?mg B(a)P per kg body weight once a week orally for the same period. B(a)P-treated mice suffered from depression and ascites, and macrocytic normochromic anemia was recorded at the 16th and 30th week. There was marked leukocytosis with lymphocytosis at the early stage of the experiment, followed by leukopenia, lymphopenia, and neutropenia at the end of the experiment. Monocytes and arginase activity were elevated throughout the experiment. Alpha feto-protein was detected only in the experimental groups in the 30th week of the experiment. A marked increase in lipid peroxides associated with a decrease in reduced glutathione and glutathione-S-transferase (GST) activity was observed in liver homogenate of the B(a)P-exposed animals. Residues of B(a)P were detected in liver tissue with a concentration parallel to the B(a)P dose level. In conclusion, B(a)P caused abnormal changes in the hemogram, evidence of tumor formation through B(a)P-induced oxidative stress, and it was accumulated in the liver tissue of mice.     

Oxidative stress mediated cytotoxicity of TiO2 nano anatase in liver and kidney of Wistar rat

This study examined the adverse effects of TiO₂ nanoparticle (nano-TiO₂) on the kidney and liver of Wistar rats. Changes of serum biochemical parameters and pathological lesions indicated that liver and kidney were significantly affected in animals treated with 50?mg?kg^?1 of nano-TiO₂. The inverse relationship between the level of reactive oxygen species and the activities of superoxide dismutase, catalase, and glutathione peroxidase indicates that nano-TiO₂ induces oxidative stress. A significant increase in the apoptosis of liver and kidney in a dose-dependent manner was also observed. The ultrastructural observations confirmed the internalization of nano-TiO₂ and their direct involvement in the mitochondria-mediated cytotoxicity. Data indicated that nano-TiO₂ induce oxidative stress which produces genotoxicity such as oxidative DNA damage, micronuclei (MN) induction, and cell apoptosis in liver and kidney.     

Testicular damage after chronic exposure to carbendazim in male goats

The present investigation was aimed to determine the effect of chronic exposure of carbendazim on cellular changes in testes of male goats. The goats were randomly divided into two groups, control and treatment (N?=?7 each). The treatment group was exposed to carbendazim at the dose rate of 50?mg?kg^?1 body weight per day orally, once daily for 180 consecutive days. Testes were removed from control and experimental animals surgically on the 90th, 120th, and 180th day. On the 180th day of the treatment, a maximum number of seminiferous tubules became atrophic, and vacuolization of germinal epithelium, and sloughing of the germinal epithelium and sertoli cells was more marked as compared to days 90 and 120. Some of the seminiferous tubules were devoid of germinal cells. These pathological findings were supported by ultrathin and electron microscopic examination. On the basis of the present investigation it could be concluded that chronic exposure of carbendazim in male goats did not allow proper maturation of testis.