Inhalation Of Organic Solvents Research Articles

Operator care and eco-concerned development of a fast, facile and economical assay for basic nitrogenous drugs based on simplified ion-pair mini-scale extraction using safer solvent combined with drop-based spectrophotometry

A fast, facile, and economical assay for basic nitrogenous drugs has been developed based on the mini-scale extraction of the drug–dye ion pair complex combined with the use of safe-for-analyst and eco-friendlier organic extractant and drop-based micro-spectrophotometry. Instead of using large volume devices, the extraction was simply carried out in typical 1.5mL microcentrifuge tubes along with the use of micropipettes for accurate transfer of liquids, vortex mixer for efficient partitioning of solutes and benchtop centrifuge for rapid phase separation. In the last step, back-extraction was performed by using the microvolume of acidic solution in order to concentrate the colored species into a confined aqueous microdrop and to keep the analyst away from unwanted contact and inhalation of organic solvents during the quantitation step which was achieved by using cuvetteless UV–vis micro-spectrophotometry without any prior dilutions. Using chlorpheniramine maleate as a representative analyte and n-butyl acetate as a less toxic and non-ozone depleting extractant, the miniaturized method was less laborious and much faster. It was accurate, precise and insensitive to the interferences from common excipients. Notably, it gave the assay results of drug in tablets and oral solution comparable to the large-scale pharmacopeial method while the consumption of organic solvents and the release of wastes were lowered by 200–400 folds.

Maternal and fetal blood and organ toluene levels in rats following acute and repeated binge inhalation exposure

Inhalation of organic solvents is a persistent form of drug abuse with particular concern being the abuse of inhalants by women of child-bearing age. While studies have begun assessing postnatal outcomes of offspring exposed prenatally to inhalants, relatively little is known about the distribution of toluene in blood and body tissues of pregnant, inhalant-abusing women, or in the fetuses. The present study assessed the tissue toluene levels attained following brief toluene exposures using a pre-clinical rat model of maternal inhalant abuse. Timed-pregnant Sprague–Dawley rats were exposed to toluene at 8000 or 12,000 parts per million (ppm) for 15, 30 or 45 min/exposure. Exposures occurred twice each day from gestational day 8 (GD8) through GD20. Immediately following the second exposure on GD8, GD14 and GD20 blood was taken from the saphenous vein of the dams. Following saphenous vein blood collection on GD20, dams were sacrificed and trunk blood was collected along with maternal tissue specimens from cerebellum, heart, lung, kidney and liver. The placenta, amniotic fluid and fetal brain were also collected. Results demonstrated that maternal saphenous blood toluene levels increased as the inhaled concentration of toluene and duration of exposure increased. The maternal cerebellum, heart, kidney and liver appeared to be saturated after 30 min on GD20 such that toluene levels in those organs were equivalent across all ambient concentrations of inhaled toluene. Toluene levels also increased in fetal brain as the inhaled concentration of toluene increased and in placenta and amniotic fluid as the duration of exposure increased. Toluene levels in all tissues at GD20, except maternal lung and amniotic fluid, were higher than in maternal saphenous blood suggesting that toluene concentrated in those organs. Measurement of toluene levels in blood and other tissues following repeated toluene exposure demonstrated that toluene readily reaches a variety of potential sites of action throughout the maternal–placental–fetal unit.

Prenatal diagnosis of schizencephaly after inhalation of organic solvents

Prenatal diagnosis of schizencephaly after inhalation of organic solvents

Effects of toluene inhalation on detection of auditory signals in rats

Inhalation of organic solvents can affect vigilance and reaction time in humans. An animal model of vigilance was designed to assess the effects of toluene on these processes. Adult male Long-Evans rats were trained to detect auditory signals (20-msec increases in the intensity of white noise). Two to 4 s after each signal (or blank period), two retractable levers were inserted into the test chamber. A press on one lever after a signal and on the other lever after a blank resulted in the delivery of food. Signal detection analysis showed that sensitivity (Sensitivity Index, SI) and response bias (Responsivity Index, RI) increased with signal intensity, indicating that loud signals were more detectable than soft signals and that the animals' criterion for responding “signal” increased with signal intensity. Response latency for correct choices was faster for signal trials than for blank trials. Toluene vapor was added to the airstream of these chambers at concentrations of 0, 1000, 1500, or 2000 ppm, either 10 or 30 min before testing and for the duration of each 1-h test. In air, SI increased across the duration of the test; this within-session improvement was reversed by toluene. RI did not change in air; it was decreased by toluene at the beginning of each exposure session, returned to the control level during exposure to 1000 and 1500 ppm toluene and exceeded air control after 40 min exposure to 2000 ppm toluene. Latency increased monotonically across toluene concentrations and time on test. Neither signal intensity nor the duration of toluene exposure before testing altered these effects of toluene. SI, RI, and latency baselines were recovered after toluene exposure indicating that no persistent effects of toluene were detectable. This conclusion was supported by data from other rats showing that toluene exposure (2000 ppm for 2 h/day for 4 consecutive days) did not affect auditory thresholds, as determined by reflex modification of an acoustic startle response using a 16 kHz tone as a prepulse stimulus, 7 or 17 days after exposure to toluene. Finally, rats tested immediately or 20 min after exposure to 0, 1000, 1500, or 2000 ppm toluene were not affected by the vapor, indicating that the impairment observed during toluene inhalation did not persist beyond the period of exposure.

Tolerance During Inhalation of Organic Solvents

Inhalation of several different halogenated solvents stimulated motor activity in mice. During prolonged exposure acute tolerance developed. The development of tolerance depended both on the schedule of exposure, and on the solvent. Exposure to trichloroethylene induced both stimulation and tolerance while the same degree of stimulation induced by 1,1,1-trichloroethane caused no tolerance. Thus the mechanisms which induce stimulation do not always initiate tolerance. Slow steady increases in the concentration of trichloroethylene could be maintained for several hours without any stimulation of motor activity. At the end of such exposures concentrations were reached which, if applied directly, would have induced considerable stimulation. Thus tolerance may develop without motor stimulation. Inhalation of ethanol also stimulated motor activity initially. During constant exposure the stimulation was followed by a considerable reduction in motor activity. This resulted in a hypoactive period, which in turn was followed by a second increase in motor activity, indicating the existence of not only two but several counteracting mechanisms. Development of metabolites with sedative effects counteracting the stimulating effect of the pure solvents seems to be one explanation for the results.

"Huffer's" Neuropathy

INSULT to the human peripheral nervous system caused by exposure to organic compounds is well known. The epidemic occurrence of triorthocresyl phosphate (TOCP) neuropathy and acrylamide neuropathy are two examples.^1,2Further, the occurrence of peripheral neuropathy after inhalation of organic solvents has been reported. For example, accidental industrial exposure to n-hexane³and methyl butyl ketone⁴has resulted in neuropathy. In addition, deliberate "sniffing" of glue containing n-hexane and toluene has resulted in a predominantly motor neuropathy with severe neurogenic atrophy.⁵ We report the occurrence of severe peripheral neuropathy in seven men who repeatedly inhaled a commercially available lacquer thinner for the euphoric sensation, ie, "high," it produces. This inhalation is called "<i>huffing</i>." Because of the general uniformity of clinical onset, progression, and physical findings, these cases are reported as a group. Aspects of individual cases of special neurologic interest will be reported later with the results