An experimental study on the combined effects of n-hexane and toluene on the peripheral nerve of the rat.

An electrophysiological study was undertaken to determine whether toluene affected the neurotoxicity of n-hexane. Separate groups of eight rats were exposed to 1000 ppm n-hexane, 1000 ppm toulene, 1000 ppm n-hexane plus 1000 ppm toluene, of fresh air in an exposure chamber for 12 hours a day for 16 weeks. The body weight, MCV, DL, MNCVs were measured before exposure, after four, eight 12, and 16 weeks exposure; and four weeks after exposure was discontinued. Exposure to 1000 ppm n-hexane considerably impaired the function of the peripheral nerve, but exposure to a mixture of 1000 ppm n-hexane plus 1000 ppm toluene resulted in only slight impairment; 1000 ppm toluene had little effect. These results strongly suggest that toluene decreases the toxic effects of n-hexane on the peripheral nerve.     

Comparison of blood and brain toluene concentrations and circulating triglyceride levels resulting from acute and repeated exposures in rats

Male Sprague-Dawley rats were exposed by inhalation to 2500 ppm toluene three hours per day, five days per week for three weeks. Blood and brain toluene concentration and circulating triglyceride levels were measured after one day, one week, two weeks and three weeks exposure. A consistent reduction in mean body weight gain was found in the toluene-exposed rats compared to controls as early as three days following initiation of exposure. During the second and third exposure week, the toluene-exposed rats exhibited marked salivation during the exposure periods. A dramatic decrease in brain and blood toluene levels occurred between the second and third exposure weeks. Also, an inverse relationship between circulating triglyceride levels and blood and brain toluene concentrations was found in the exposed rats. Plausible mechanisms for tolerance development and the inverse relationship to circulating triglycerides are offered including induction of hepatic mixed function oxidase activity and alterations in brain biomembrane lipid composition.     

Changes of n-hexane neurotoxicity and its urinary metabolites by long-term co-exposure with MEK or toluene

Summary It is well known that the neurotoxicity of n-hexane may be modified upon co-exposure with other organic solvents. In order to elucidate this mechanism further, rats were exposed to 500ppm n-hexane, 500ppm n-hexane plus 500ppm methyl ethyl ketone (MEK), 500ppm n-hexane plus 500ppm toluene, or air only for 8h per day for 33 weeks. The body weight, motor nerve conduction velocity (MCV) and distal latency (DL) were determined before exposure and after 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. From each group one rat was histologically examined after 33 weeks of exposure. To establish a relationship between the n-hexane neurotoxicity and changes in biotransformation, urinary metabolites (2-hexanol, methyl n-butyl ketone (MBK), 2,5-hexanedione, 2,5-dimethylfuran, and -valerolactone) were measured by gas chromatography on the first exposure day, and after 1, 2, 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. The total amounts of metabolites of n-hexane in the urine significantly decreased upon co-exposure of n-hexane, with MEK as well as with toluene, in comparison with those of animals exposed to n-hexane alone. 2,5-Hexanedione, which is considered the ultimate neurotoxic metabolite of n-hexane, also decreased. Electrophysiological and histological studies did not reveal statistically significant differences between any two groups among the four groups. It is considered that the present results might explain the combined effects of n-hexane and toluene which decrease n-hexane neurotoxicity, but do not explain those of n-hexane and MEK. Therefore, other mechanisms of the combined effects of n-hexane and MEK should be studied.     

Combined effects of toluene and hot microclimate on human body

It is shown in the paper that sensitivity of human organism to the toxic action of toluene is not changed under exposure to the microclimate, producing allowable thermal state, and is increased under exposure to the heating microclimate leading to the development of maximum thermal state. Under toluene exposure in the concentration 300 mg/m3 resistance to the heating microclimate under the conditions of joint exposure to these factors is reduced, which is manifest in an earlier onset of the maximum thermal state in people under observation.     

Hematotoxic effects in the rat of a toluene dinitro derivative after short-term exposure

3,5-Dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene (DNCTT) is an intermediate in the synthesis of dinitroaniline herbicides and was involved in an episode of ground water pollution in 1977. The compound presents a high environmental persistence, which may have possible implications concerning public health. In one experiment male Sprague-Dawley rats were administered DNCTT for 3 days at a dose level of 150 mg/kg body wt by oral gavage. Groups of rats were sacrificed up to 10 days after the end of the administration, at 2-day intervals. Methemoglobin was increased up to Day 7; white blood cells were also increased both in peripheral blood and in bone marrow smears. Spleen relative weights were observed to increase slightly at Days 7 and 10; microscopic examination revealed marked congestion with an increased density of the spleen's white pulp. In a similar scheduled experiment, but at a dose level of 300 mg/kg body wt, the bone marrow white cell series were not affected initially, but were affected after 3 days at the end of the administration. DNCTT has a definite effect on white cells.     

Combined and isolated effects of toluene and general vibration on the body

The paper presents the results of an investigation of the isolated and combined effect of toluene (at the level of the maximum pennissible concentration (MPC), general vibration, and its concomitant noise on experimental animals (rats). The changes detected in the morphofunctional status of the cardiovascular system are indicative of the isolated and combined effect of toluene, general vibration, and noise at the level of MPC on the morphology of the myocardium and aorta of experimental animals.     

Tissue concentrations of chlordanes in mice after long-term exposures to technical grade chlordane at indoor air levels

We determined concentrations of chlordanes (5 chlordane compounds and 2 metabolites) in tissues and organs of mice following a prolonged exposure to Chlordane (technical grade chlordane) at levels as low as those in indoor air. After exposure to 4.22–11.36 μ g/m³ Chlordane (total of 5 compounds) in the air for 1–6 months, 6.44–13.00 ppm chlordanes (total of 7 compounds) were detected in mice (2 tissues and 6 organs). The adipose tissue among the 2 tissues / 6 organs examined contained the highest chlordanes. The ratio of the adipose tissue chlordanes to the liver chlordanes was approximately 5.6 times, followed by the muscle (0.9), lungs (0.4), kidneys (0.4), heart (0.3), spleen (0.2) and brain (0.1). In addition, trans-nonachlor, oxychlordane and heptachlorepoxide in chlordanes were at a high level. The level of Chlordane exposure (dose) and the level of chlordanes accumulation in each tissue or organ of the mice except for the heart were closely correlated (r=0.9388-0.7130), and showed a linear relationship. The tendency of chlordanes accumulation in light of the linear relationship was adipose ≫ liver ≥ muscle. Thus, even with a low level of Chlordane in indoor air, chlordanes may be steadily accumulated in the bodies of human residents with prolonged exposure similarly. The present findings suggest that it is necessary to investigate die risk of organochlorine chemicals contamination in indoor air at prolonged exposure.     

Comparison of blood toluene levels after inhalation and oral administration

The purpose of this investigation was to compare blood toluene levels in Sprague-Dawley rats after oral and inhalation administration. Groups of 30 rats were dosed by gavage with 86.7, 217, 433, or 867 mg toluene/kg body wt or exposed for up to 6 hr, 5 rats per exposure, to an atmosphere of either 200 or 1000 ppm toluene. Blood was sampled by cardiac puncture from 5 rats in each of the six dose groups at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hr after gavage dosing or the beginning of the inhalation exposure. Blood toluene levels were analyzed. A four-parameter model was fitted to the blood toluene levels of the orally dosed rats. The area under the curve generated by this model, representing total blood toluene concentration over 6 hr, was calculated and compared to the area under the blood toluene curve for the 6-hr inhalation exposure. Integrated areas from the two routes of exposure were used for direct comparison of oral and inhalation exposures. The data demonstrate that gavage dosing can be used to approximate inhalation exposure to toluene.     

Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene of MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and gamma-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pesticides on cell survival in liver and brain rat tissues

Pesticides are the main environmental factor associated with the etiology of human neurodegenerative disorders such as Parkinson's disease. Our laboratory has previously demonstrated that the treatment of rats with low doses of dimethoate, zineb or glyphosate alone or in combination induces oxidative stress (OS) in liver and brain. The aim of the present work was to investigate if the pesticide-induced OS was able to affect brain and liver cell survival. The treatment of Wistar rats with the pesticides (i.p. 1/250 LD50, three times a week for 5 weeks) caused loss of mitochondrial transmembrane potential and cardiolipin content, especially in substantia nigra (SN), with a concomitant increase of fatty acid peroxidation. The activation of calpain apoptotic cascade (instead of the caspase-dependent pathway) would be responsible for the DNA fragmentation pattern observed. Thus, these results may contribute to understand the effect(s) of chronic and simultaneous exposure to pesticides on cell survival.     

Effect of an oral contraceptive on alpha-tocopherol levels in rat tissues

The distribution of alpha-tocopherol was studied in female rats receiving .052 mg/day Enovid E for 4 days, and maintained on Vitamin E deficient, adequate, or enriched (10%) diets. The administration of Enovid produced slight increases of alpha-tocopherol in the liver and ovaries of Vitamin-E-deficient animals, and decreases of alpha-tocopherol in the plasma, erythrocytes, adrenals, and kidneys of Vitamin-E-supplemented rats. The magnitude of response of different tissues varied with increasing levels of dietary tocopherol. The results support previous findings on the effects of oral contraceptives on plasma cholesterol levels and lipoprotein distribution.