• Biomedical Science Letters
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• v.6 no.4
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• pp.245-251
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• 2000

In order to search the target organ of cylclohexane toxicity, the rats were intraperitoneally treated with cyclohexane (1.56 g/kg of body wt.) four times every other day. In the increasing rate of organ weight per body weight (%) in cyclohexane-treated animals, the lung was highest among the liver, spleen, small intestine, stomach, heart and kidney. And in the decreasing rate of glucose-6-phosphatase (G-6-Pase) activity in each organ, that of lung was also highest among all organs. Lung MDA content was significantly increased (p<0.05) by the cyclohexane treatment. On the other hand, microsomal aniline hydroxylase activity in lung tissue both of control and cyclohexane-treated rats was greatly low as could be scarcely measured, but that in liver possessing high activity was significantly increased (p<0.05) in cyclohexane-treated rats compared with control. Alcohol dehydrogenase activity in lung was markedly higher than that of liver and the latter was significantly (p<0.05) increased by the cyclohexane treatment. In conclusion, cyclohexane treatment to the rats showed mainly lung toxicity and it may be responsible for cyclohexanon, cyclohexane metabolite, distributed from liver.

• Journal of Environmental Health Sciences
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• v.28 no.2
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• pp.71-80
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• 2002

To evaluate the skin toxicity of topical cyclohexane application (25mg/$\textrm{cm}^2$) was sequentially applied to the rat skin for four days. On the histopathological findings in the light micrographs, neutrophils and engulfed neutrophils are seen, and many cytoplasmic processes were appeared in proliferated layer whereas in the dermis area, increased numbers of fibroblast, accumulation of neutrophil and lipid droplets are demonstrated. On the other hand, applying the cyclohexane to the rat skin led to the remarkable rise of cutaneous xanthine oxidase activity and similar activities of superoxide dismutase and glutathione peroxidase and glutathione content and declined activity of glutathione S-transferase compared with control group. Especially the remarkably decreased activity of aniline hydroxylase (AH) was appeared in skin as little as scarcely determined. Furthermore, the applying the cyclohexane to skin led to the significantly increased activity of hepatic AH and alcohol dehydrogenase. These results indicate that oxygen free radical and intermediate metabolite of cyclohexane may be responsible for structural changes in skin by cyclohexane application to rat skin.

• Biomedical Science Letters
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• v.11 no.4
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• Biomedical Science Letters
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• v.12 no.4
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• pp.361-370
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• 2006

To evaluate an effect of pathological liver damage on the conjugation of cyclohexane metabolites, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1 ml/100 g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones. To these liver damaged animals, cyclohexane (a single dose of 1.56 g/kg body weight, i.p.) was administered at 48 hr after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hr after injection of cyclohexane. The cyclohexane metabolites, cyclohexanol (CH-ol), cyclohexane-1,2-diol (CH-1,2-diol), cyclohexane-1,4-diol (CH-1,4-diol), and their glucuronyl conjugates and cyclohexanone were detected in the urine of cyclohexane treated rats. The urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged.ats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to CH-ol analogues compared with normal group. Futhermore, CH-1,2 and 1,4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. On the other hand, the increasing rate of activities of hepatic cytochrome P450 dependent aniline hydroxylase, alcohol dehydrogenase and urine diphosphate glucuronyl transferase was higher in 17 times $CCl_4$-treated rats compared with normal and $CCl_4$ 10 times injected animals. Taken all together, it is assumed that an increased urinary excretion amount of cyclohexane metabolites in liver damaged rats might be caused by an increase in the activities of cyclohexane metabolizing enzymes. And enhanced conjugating ability of CH-ol in liver damaged animals and novel finding of conjugating form of CH-1,2 and 1,4-diol might be caused by increase in the activity of hepatic diphosphouridine glucuronyltransferase.

• Toxicological Research
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• v.18 no.2
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• pp.159-165
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• 2002

Recently, we reported (korean J. Biomed. Lab. Sci., 6(4): 245-251, 2000) that cyclohexane (l.56 g/kg of body wt., i.p.) administration led to lung injury in rats. However the detailed mechanism remain to be elucidated. This study was designed to clarify the mechanism of lung damage induced by cyclohexane in rats. First, lung damage was assessed by quantifying bronchoalveolar lavage fluid (BAL) protein content as well us by histopathological examination. Second, activities of serum xanthine oxidase (XO), pulmonary XO and oxygen free radical scavenging enzymes. XO tope conversion (O/D + O, %) ratio and content of reduced glutathione (GSH) were determined. In the histopathological findings, the vasodilation, local edema and hemorrhage were demonstrated in alveoli of lung. And vascular lumens filled with lipid droplets, increased macrophages in luminal margin and increased fibroblast-like interstitial cells in interstitial space were observed in electron micrographs. The introperitoneal treatment of cyclohexane dramatically increased BAL protein by 21-fold compared with control. Cyclohexane administration to rats led to a significant rise of serum and pulmonary XO activities and O/D + O ratio by 47%,30% and 24%, respectively, compared witれ control. Furthermore, activities of pulmonary oxygen free radical scavenging enzymes such as superoxide dismutase, glutathione peroxidase and glutathione S-transferase, and GSH content were not found to be statistically different between control and cyclohexane-treated rats. These results indicate that intraperitoneal injection of cyclohexane to rats may induce the lipid embolism in pulmonary blood vessel and lead to the hypoxia with the ensuing of oxygen free radical generation, and which may be responsible for the pulmonary injury.

• Toxicological Research
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• v.19 no.2
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• pp.105-114
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• 2003

TO evaluate an effect of cyclohexane treatment on the degree of liver damage, rats were induced liver damage with 10 or 17 times $CCl_4$ injection (0.1 m1/100 g body wt., 50% $CCl_4$ dis-solved in olive oil) at intervals of every other day. Cyclohexane (1.56 g/kg body wt., i.p.) was administrated to the animals at 48 hours after the last pretreatment of $CCl_4$ . Rats were sacrificed at 4 hours after injection of cyclohexane. On the basis of histopathological findings, liver weight/body weight (LW/ BW, %), activities of serum alanine aminotransferase (ALT), xanthine oxidase (XO) and akaline phosphatase (ALP), and contents of liver protein and manlondialdehyde (MDA), $CCl_4$ -pretreatment induced liver damage. And $CCl_4$ 17 times treated group showed more severe liver damage than $CCl_4$ 10 times treated group. Administration of one dose of cyclohexane to $CCl_4$ 10 times treated animals resulted in the enhanced liver damage; liver necrosis with proliferation of fibroblast and bile duct abnormality, and increase in hepatic MDA content and the activities of serum ALP and ALT, But the enhanced liver damage was not found in $CCl_4$ 17 times treated animals. Serum cyclohexanone concentrations at 4 or 8 hours after injection of cyclohexane were higher in all liver damaged groups than normal group and were somewhat higher In $CCl_4$ 17 times treated animals than $CCl_4$ 10 times treated ones. Among the oxygen free radical metabolizing enzymes, hepatic cytochrome P45O dependent aniline hydroxylase (CYPdAH) activity in cyclohexane metabolizing enzyme system was meaningfully increased by the injection of cyclohexane to the liver damaged rats, with increased Vmax and high affinity to aniline. LW/BW (%) and activities of serum XO and ALT were more significantly increased in liver damaged groups than normal group by administration of cyclohexanone. In conclusion, it is assumed that an enhancement of liver damage by injection of one dose of cyclohexane to liver damaged animals might be caused by oxygen free radicals and cyclohexanone.

• Biomedical Science Letters
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• v.9 no.2
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• pp.93-98
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• 2003

To investigate the cyclohexane and xylene mixture treatment on the liver damage, the rats were treated by the mixture of cyclohexane and xylene (CH＋X) and then, liver damage was demonstrated by liver function findings based on liver weight/body weight, serum level of alanine aminotransferase (ALT), xanthine oxidase (XO) and then compared with cyclohexane treated group (CH group) and xylene-treated group (X). The CH＋X group showed merely severer liver damge than CH or X group. On the other hand, CH＋X group showed lower activity of hepatic cytochrome P-450 dependent aniline hydroxylase (CYPdAH) than CH or X group, but no statical differences were demonstrated among three experimental groups. Especially the hepatic GSH content was merely declined than CH or X group and the activity of hepatic GST was higher in CH＋X group than CH or X group. In conclusion, cyclohexane and xylene mixture treated animals showed merely severer liver damage than cyclohexane or xylene treated group and such a fact may be caused by inhibition of cyclohexane or xylene metabolism and oxygen free radical.

• Journal of the Korean Institute of Gas
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• v.15 no.2
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• pp.75-81
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• 2011

For the safe handling of cyclohexane, the explosion limit at $25^{\circ}C$ and the temperature dependence of the explosion limits were investigated. Flash point and AIT(autoignition temperature) for cyclohexane were experimented. By using the literatures data, the lower and upper explosion limits of cyclohexane recommended 1.0 Vol% and 9.0 Vol%, respectively. Moreover lower flash points of cyclohexane recommended $-20^{\circ}C$. It was measured relationship between the AITs and the ignition delay times by using ASTM E659-78 apparatus for cyclohexane, and the experimental AIT was $255^{\circ}C$. The new equations for predicting the temperature dependence of the explosion limits of cyclohexane is proposed. The values calculated by the proposed equations were a good agreement with the literature data.

• Proceedings of the Korean Environmental Health Society Conference
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• 2003.06a
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• pp.157-157
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• 2003

To evaluate an effect of pathological liver damage on the cyclohexane metabolism, rats were pretreated with 50% $CCl_4$ dissolved in olive oil (0.1$\mell$/100g body weight) 10 or 17 times intraperitoneally at intervals of every other day. On the basis of liver function and histological findings, the animals pretreated with $CCl_4$ 10 times were identified as acutely liver damaged ones and the animals pretreated with $CCl_4$ 17 times were identified as severly liver damaged ones, with fibrosis, biliary abnormality and mild injury both in the kidneys and the lungs. To these liver damaged animals, cyclohexane (a single dose of 1.56g/kg body weight, i.p.) was administrated at 48 hours after the last injection of $CCl_4$. The rats were sacrificed at 4 or 8 hours after injection of cyclohexane. The cyclohexane metabolites; cyclohexanol (CH-ol), cyclohexane-1, 2-diol (CH-1, 2-diol), cyclohexane-l, 4-diol (CH-1, 4-diol), and their glucuronyl conjugates and cyclohexanone (CH-one) were detected in the urine of cyclohexane treated rats. After cyclohexane treatment, the serum levels of CH-ol and CH-one were remarkably increased at 4 hours and then decreased at 8 hours in normal group. Whereas in liver damaged rats, these cyclohexane metabolites were higher at 8 hours than at 4 hours. The excretion rate of cyclohexane metabolites from serum into urine was more decreased in liver damaged animals than normal group, with the levels of excretion rate being lower in $CCl_4$ 17 times injected animals than 10 times injected ones. However, it was interesting that the urinary concentration of cyclohexane metabolites was generally more increased in liver damaged animals than normal ones, and the increasing rate was higher in $CCl_4$ 17 times injected rats than 10 times injected ones. And liver damaged rats, especially $CCl_4$ 17 times treated ones, had an enhanced ability of glucuronyl conjugation to cyclohexanol analogues compared with normal group. Futhermore, CH-1, 2 and 1, 4-diol were all conjugated with glucuronic acid in $CCl_4$ 17 times injected animals. In conclusion, the metabolic rate of cyclohexane was unexpectably accelerated and it may be caused by physiological adaptation of adjacent intact hepatocyte in damaged liver.

• Journal of the Korean Graphic Arts Communication Society
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• v.20 no.1
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• pp.91-101
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• 2002

An acid amplifier is defined as an acid-generating agent which is decomposed autocatalytically to produce new strongly acidic molecules in a non-liner manner, The addition of the acid amplifiers to conventional chemically amplified photoresists consisting of photoacid generators and acid-sensitive polymers result in the improvement of photosensitivity due to the amplified generation of catalytic acid molecules as a result of the decomposition of acid amplifiers. We synthesized and evaluated 1-hydroxy-4-tosyloxy cyclohexane(AA-1) and 1,4-ditosyloxy cyclohexane(Ah-2) as novel acid amplifiers. The acid amplifiers(AA-1, AA-2) showed reasonable thermal stability for resist processing temperature. As estimated by the sensitivity curve, tort-butyl methacrylate homopolymer(ptBMA) film doped with AA-1 or 2 exhibited much higher photosensitivity than ptBMA film without AA-1 or 2. And AA-1 showed higher effect than AA-2 on enhancing photosensitivity of ptBMA film.