Animals ; Chromatography, Gas ; methods ; Hexanones ; blood ; Mice

Hexanes ; Hexanones ; blood ; Humans ; Occupational Exposure

Hexane is a widely used organic solvent in industry, and chronic hexane poisoning is the main occupational toxic lesion in China. In particular, axonal and myelin lesions in the distal thick fibers of the peripheral nervous system may be caused by 2, 5-hexanedione (2, 5-HD), an intermediate metabolite of n-hexane in humans. Hexane has toxic effects not only on the nervous system but also on the liver, kidneys, and reproductive organs. In this paper, we review the progress of research on the mechanism of n-hexane toxic neuropathy.
Humans ; Hexanes/toxicity* ; Hexanones ; Industry ; Solvents

OBJECTIVETo establish a method for determination of 2,5-hexanedione in urine by headspace solid-phase microextraction-gas chromatography.

METHODSAfter extraction by solid-phase microextraction head, 2,5-hexanedione in urine was determined by gas chromatography and was quantified by external standard method.

RESULTSThe concentration of 2,5-hexanedione in urine showed a linear relationship within the range of 0.1-20.0 µg/ml. The regression equation was y=261.36x-1.903 3, r=0.999 2. The minimum detectable concentration was 0.01 µg/ml. The recovery rate was 92.6%-97.1%, with a relative standard deviation (RSD) of 3.3%-5.8%. The intra-day and inter-day RSDs were 3.8%-6.2% and 4.7%-6.3% respectively.

CONCLUSIONThis determination method has no requirement for organic solvents, features simple and rapid operation, possesses higher detection sensitivity, and applies well to the determination of 2,5-hexanedione in urine.

Chromatography, Gas ; Hexanones ; urine ; Humans ; Sensitivity and Specificity ; Solid Phase Microextraction

OBJECTIVETo investigate the relationship between formation of pyrrole adducts and concentration of 2, 5-hexanedione (2, 5-HD) and to provide an experimental basis for the study on toxicity of n-hexane.

METHODSSerum samples were collected from normal persons and were then filtered and sterilized. They were mixed with 2,5-HD to obtain sera with final 2, 5-HD concentrations of 10, 25, 50, 100, and 200 mg/L, and blank serum was also prepared. The sera were cultured at 37°C and taken at different time points. Colorimetry was used to quantify the pyrrole adducts formed in sera, and gas chromatography was used to measure the remaining 2, 5-HD levels in sera.

RESULTSThe content of pyrrole adducts increased as the culture proceeded and was dependent on the dose of 2, 5-HD; at the end of the experiment, the content of pyrrole adducts differed significantly across all concentration groups (P < 0.5). The concentrations of 2,5-HD decreased as the culture proceeded; at the end of the experiment, the concentrations of 2, 5-HD, from the highest to the lowest, decreased by 29%, 55%, 22%, 44%, and 40%, respectively. The decrease in 2, 5-HD had a positive correlation with the increase in pyrrole adducts, and the correlation coefficients for 200∼10 mg/L 2, 5-HD were 0.865, 0.697, 0.835, 0.823, and 0.814, respectively.

CONCLUSIONThe content of formed pyrrole adducts increases as the concentration of 2,5-HD rises; there is a positive correlation between the decrease in 2, 5-HD and the increase in pyrrole adducts in human serum.

Hexanones ; chemistry ; Humans ; Oxidation-Reduction ; Pyrroles ; chemistry ; Serum ; chemistry

Gas Chromatography-Mass Spectrometry ; methods ; Hexanones ; urine ; Humans ; Sensitivity and Specificity

Capillary Electrochromatography ; Chromatography, Gas ; methods ; Hexanones ; urine ; Humans ; Occupational Exposure

OBJECTIVETo investigate the effects of garlic oil (GO) on n-hexane metabolized to 2, 5-hexanedione (2, 5-HD) in mice.

METHODSAdult healthy Kunming-mice were treated with n-hexane and GO. The serum was obtained and extracted with ethyl acetate, and the levels of the serum 2, 5-HD were determined by gas chromatography.

RESULTS(1) The concentration of 2, 5-HD in serum increased firstly after a single exposure to n-hexane (4 000 mg/kg). The peak value occurred at 10 hours after n-hexane treatment, but could hardly be detected at 20 h. (2) There was no 2, 5-HD in serum of control mice. The content of 2, 5-HD in serum increased along with the exposure dose of n-hexane. The serum 2, 5-HD contents of the 2000, 4000 and 6000 mg/kg groups mice were 8.04, 16.68 and 22.38 microg/ml at 8 h in pretreated mice, respectively, and showed significant dose-effect relationship. (3) When the different age mice were exposed to the same dose of n-hexane, the contents of 2, 5-HD in serum were significantly different after 8 hours (P<0.05). The serum 2, 5-HD level of the 5 weeks old mice (22.83 microg/ml) was much higher than the 4 (19.59 microg/ml) and 6 (16.42 microg/ml) weeks old mice. (4) When the different gender mice were exposed to the same dose of n-hexane, the concentration of 2, 5-HD in serum of female mice (13.22 microg/ml) was higher than that of the female mice (10.34 microg/ml, P<0.05). (5) GO significantly inhibited the increase of the serum 2, 5-HD levels of both the pretreatment and post-treatment groups treated with 80 mg/kg n-hexane respectively, but the pretreatment with GO exhibited the more suppressive effects than the post-treatment (P>0.05). Compared with the n-hexane group, the concentrations of serum 2, 5-HD in GO-pretreated groups mice decreased by 16.2%, 20.8%, 22.8% (P<0.05) and 32.1% (P<0.01), respectively, and showed significant dose-effect relationship.

CONCLUSIONThe serum content of 2, 5-HD, the metabolite of n-hexane, is different in different genders and age mice after exposed to the same dose of n-hexane. GO can effectively inhibit the production of n-hexane metabolized to 2, 5-HD in mice serum.

Allyl Compounds ; chemistry ; Animals ; Biotransformation ; drug effects ; Female ; Hexanes ; pharmacokinetics ; Hexanones ; blood ; Male ; Mice ; Sulfides ; chemistry

OBJECTIVETo investigate effects of garlic oil (GO), age and sex on n-hexane metabolism in rats.

METHODSThe Wistar rats were used as experimental animals. (1) Intragastric administration: n-hexane group (3000 mg/kg n-hexane), GO treated group (80 mg/kg GO ig. an hour earlier than 3000 mg/kg n-hexane), then blood was taken from tails of rats at 8, 12, 16, 20, 24, 28, 32 h points after n-hexane administration. (2) Intraperitoneal injection: n-hexane group (1000 mg/kg n-hexane), GO treated group (80 mg/kg GO ig. an hour earlier than 1000 mg/kg n-hexane), then took blood was taken from tails of rats at 8, 12, 16, 20, 24, 28 h points after n-hexane injection. (3) 7 rats each group of 6, 8, 10 weeks age were administrated by 3000 mg/kg n-hexane intragastrically, then were taken blood from tails at 16, 20, 24 h points after administration. (4) 7 male and 7 female rats of 8 weeks age were administrated by 3000 mg/kg n-hexane intragastrically, then were taken blood from tails at 16, 20, 24, 28 h points after administration. The gas chromatography was used to determine the metabolite 2, 5-hexanedione concentration of n-hexane in serum and 2, 5-hexanedione concentration was compared between GO and no GO treated rats, different ages and different sexes.

RESULTS(1) Intragastric administration: 2, 5-hexanedione concentrations in serum of n-hexane group and GO treated group had the peak 19.2 and 12.3 µg/ml at 20h and 24 h points. Compared with n-hexane group, the serum 2, 5-hexanedione concentration of GO treated group was lower at time points prior to peak and 2, 5-hexanedione eliminating process was slower after peak. (2) Intraperitoneal injection: effects of GO on the serum 2, 5-hexanedione concentrations was very similar to intragastric administration, 2, 5-hexanedione concentrations in serum of n-hexane group and GO treated group had the peak 15.0 and 6.7 µg/ml at 12 h and 16 h points. (3) Comparison of the serum 2, 5-hexanedione concentrations of different weeks age rats: The serum 2, 5-hexanedione concentrations of 6, 8, 10 weeks age rats were 25.5, 15.0, 12.8 µg/ml each (8, 10 weeks age significantly lower than 6 weeks age) at 16 h point; at 20 h point, they were 24.7, 18.3, 15.0 µg/ml each (10 weeks age significantly lower than 6 weeks age); at 24 h point, they were 11.0, 14.7, 8.1 µg/ml each (10 weeks age significantly lower than 8 weeks age). (4) Comparisons of the serum 2, 5-hexanedione concentrations of different sex rats: the serum 2, 5-hexanedione concentrations of male and female rats were 22.5, 17.2 µg/ml each at 16 h point (different significantly); at 20, 24, 28 h points, they were 27.6, 22.9 µg/ml, 24.6, 19.1 µg/ml, 19.1, 13.8 µg/ml each (different non-significantly).

CONCLUSIONGO reduces production of 2, 5-hexanedione in serum generated by n-hexane in rats; the metabolic capacity of low age rats on n-hexane is stronger than high age ones.

Age Factors ; Animals ; Antioxidants ; pharmacology ; Female ; Garlic ; Hexanes ; metabolism ; Hexanones ; blood ; Male ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar ; Sex Factors

OBJECTIVETo investigate the dynamic changes of neurofilament contents in rat's spinal cord induced by 2, 5-hexanedione (2, 5-HD), and explore the molecular mechanism of n-hexane neuropathy.

METHODSMale Wistar rats were administered at a dosage of 400 mg/kg/day 2, 5-HD for 2, 4 and 8 weeks respectively. HD-induced neurological defects were detected and quantified using gait score, and the relative lev-els of NF-H, NF-M, and NF-L in spinal cords of rats were determined by Western Blotting.

RESULTSExposure to 2, 5-HD produced progressive gait abnormalities, which suggested that the rat model of 2, 5-HD-induced neurotoxicity was established successfully. Western-Blotting results showed that NFs content in spinal cord demonstrated a progressive decline as the intoxication continued. In the supernatant fraction, compared to the controls, NF-H con-tent decreased by 15.7%, 57.0%, and 58.0% respectively after 2, 4, and 8-week treatment with 2, 5-HD (P < 0.01); accordingly, NF-M decreased by 36.0%, 61.3%, and 65.2% respectively (P < 0.01); NF-L decreased by 20.8%, 43.9%, and 44.3% respectively (P < 0.01). In the pellet fraction, the contents of NF-H in groups of 4 and 8 weeks' exposure to HD decreased by 35.6% and 43.2%, respectively (P < 0.01), and those of NF-L decreased by 26.4% and 42.1%, respectively (P < 0.01) when compared to the control. Further-more, NF-M contents in groups of 2, 4 and 8 weeks' exposure decreased by 23.3%, 33.9%, and 63.7% respectively (P < 0.01). The NFs level in spinal cords was highly correlated with gait abnormality of treated rats as the intoxication went on. Multiple correlation coefficients of NF-H, NF-M, and NF-L content with gait score of HD-treated rat were 0.8912, 0.9282 and 0.8981 (P < 0.01) respectively.

CONCLUSIONThe declines of NFs are high-ly related to neurobehavioral abnormality of 2, 5-HD-treated animals, and involved in the development of n-hexane neuropathy.

Animals ; Disease Models, Animal ; Gait ; drug effects ; Hexanones ; toxicity ; Male ; Neurofilament Proteins ; metabolism ; Rats ; Rats, Wistar ; Spinal Cord ; drug effects ; metabolism