Sex-dependent induction of alcohol dehydrogenase activity in rats.

The glycolethers 2-methoxyethanol (2-ME), 2-ethoxyethanol (2-EE), and 2-butoxyethanol are widely used organic solvents with teratogenic, spermatotoxic, and hematotoxic effects due to the respective alkoxyacetic acid metabolites formed via alcohol dehydrogenase (ADH). ADH displays sexually dimorphic activities in adult rats, and is probably at least in part under the control of testosterone. The aim of this study was to investigate whether induction of ADH is also sex-dependent. Ethanol, 2-ME, and 2-EE were tested as inducers of hepatic and gastric ADH in female, male, and castrated male rats. The activity of hepatic ADH was higher in female than in male rats, while the activity of gastric ADH was higher in male than in female rats. The activities of ADH increased with increasing chain length of the glycolethers and alcohols. Castration of male rats led to a female pattern of ADH activity, i.e. increased activity of hepatic ADH and decreased activity of gastric ADH. Ethanol had no inducing effect on hepatic ADH in either male or female rats. 2-ME and 2-EE caused an increase in the activity of hepatic ADH in male and castrated male rats only. The present data demonstrate a different expression of ADH isoenzymes in male and female rats, and a sex-dependent induction of ADH isoenzymes. The different possible regulatory mechanisms for the different ADH isoenzymes require further investigation.

Skin symptoms in the seafood-processing industry in north Norway.

A survey of occupational skin problems, based on a questionnaire, was carried out among 883 workers in different types of seafood-processing industries in northern Norway. The prevalence of dry skin, itching, rash/eczema, chapped skin and chronic sores was significantly higher among production workers (55.6%) in the white fish-, shrimp- and salmon-processing industries, compared to administrative workers in the same industries (27.5%). Among production workers, there was a significantly higher prevalence of skin symptoms among females (60.2%) compared to males (50.1%). A strong sex division of work tasks rather than sex itself may explain this. There was no sex difference among administrative workers. Several risk factors for skin symptoms to occur are indicated. The workers are exposed to raw materials and a mixture of water and juice from the fish or shrimp, salt, detergents and disinfectants. Gloves may also cause skin problems. Major risk factors believed to cause skin symptoms were contact with raw materials, fish juice, water and gloves. The results also indicate that skin symptoms are of moderate severity and seldom interfere with working capacity.

Gender difference in the elimination of 2-methoxyethanol, methoxyacetic acid and ethoxyacetic acid in rat.

1. The elimination of 2-methoxyethanol (2-ME) and its toxic metabolite methoxyacetic acid (MAA) was studied in the male and female rat. We also studied the elimination of ethoxyacetic acid (EAA), the toxic metabolite formed by 2-ethoxyethanol (2-EE). 2. The rate of 2-ME elimination after i.p. injection of 2-ME (150 mg/kg) was significantly higher in the female compared with male. The elimination half-life was estimated to 49 +/- 10 min in the male and 28 +/- 5 min in the female. There was, however, no gender difference in the elimination of MAA after i.p. injection of 2-ME (100 mg/kg), and the elimination of MAA was markedly slower compared with 2-ME. The elimination half-life for MAA was estimated to 12.6 +/- 1.3 h in the male and 14.1 +/- 1.4 in the female. 3. The elimination half-life of EAA after i.p. injections of 100 mg/kg 2-EE was estimated to 7.6 +/- 1.1 h and 7.6 +/- 0.75 h in the male and female rat respectively. There was no gender difference in the elimination of EAA, but the rate of elimination of EAA was significantly higher compared with MAA. 4. Accumulation of the toxic metabolites MAA and EAA following frequent exposures to 2-ME and 2-EE respectively can then occur, and it remains to be determined whether there is a sex-difference in the susceptibility to toxic effects following exposure to 2-ME and 2-EE.

Elimination of methoxyacetic acid and ethoxyacetic acid in rat.

1. The pharmacokinetics of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) have been determined in the male and female rat following bolus intravenous administration at 100 mg/kg. The plasma-concentration data of MAA fitted well to a one-compartment model, and the plasma-concentration data of EAA to a two-compartment model. 2. The elimination half-life of MAA estimated from plasma data was higher in females (18.6+/-2.0 h) than in males (13.2+/-0.4 h). There was no difference in the elimination half-lives estimated from urine data. The apparent volume of distribution was lower in the male than in the female rat estimated from plasma data only, while AUC, total and non-renal clearances and the relative amount MAA excreted unchanged in urine was similar in the male and female rat. 3. Clearance of EAA is higher than of MAA, and this appears as a result of metabolic capacity. The elimination half-lives of EAA were similar in the male and female rat, 9.4+/-3.7 and 10.5+/-2.6 h respectively. AUC was higher in the female compared with the male rat. The fraction of EAA eliminated during the distribution phase was 44.0+/-15.4 and 41.0+/-17.4% in the male and female rat respectively. The initial volume of distribution, the apparent volume of distribution, total and non-renal clearance are higher in the male compared with the female rat.

[Exposure to anesthetic gases]. / Eksponering for narkosegasser.

In recent years there has been a growing awareness of possible hazards caused by anaesthetic gases in operating theatres. Our study monitored ambient nitrous oxide (N2O) levels in the operating theatres and recovery rooms at the University Hospital in Tromsø. The results show that exposure to waste anaesthetic gases occurs because of leaks in the anaesthetic equipment. The three major sources of leaks are masks, high pressure fittings and exhalation valves. Prevention of leakage from equipment is very important, and a leakage testing programme should be an essential part of the daily control strategy. Good working practices and tracheal intubation results in low exposure to nitrous oxide in the breathing zone of the anesthetic personnel. During mask anaesthesia we have observed nitrous oxide concentrations above 1500 ppm, owing to mask leakage. A closely fitting scavenging mask and good working practices lead to in lower nitrous oxide concentrations. Nitrous oxide exhalation from the patient in the recovery room is only a minor problem.

The role of liver alcohol dehydrogenase isoenzymes in the oxidation of glycolethers in male and female rats.

The glycolethers 2-methoxyethanol (2-ME), 2-ethoxyethanol (2-EE), and 2-butoxyethanol (2-BE) are used as solvents and have teratogenic, spermatotoxic, and hematotoxic effects. These glycolethers are oxidized to their corresponding alkoxyacetic acids, probably by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). This metabolic conversion of the glycolethers is a prerequisite for development of toxicity, as the toxic effects have been shown to be due to the alkoxyacetic acid metabolites. Three isoenzymes of ADH have been detected in rat tissues. The liver contains two of these isoenzymes, ADH-2 and ADH-3. It has also been shown that the activity level of ADH is strongly sex dependent, with higher activity in females than in males. In the present study, we have investigated whether one or both of the ADH isoenzymes in male and female rat livers were able to oxidize 2-ME, 2-EE, and 2-BE and whether one or both of the ADH isoenzymes in male rat liver were able to oxidize 2-pentyloxyethanol and 2-hexyloxyethanol. Our results indicated that only the ADH-3 isoenzyme effectively oxidized the glycolethers in rat liver. Both ADH-2 and ADH-3 were able to oxidize medium chain aliphatic alcohols with a chain length corresponding to the glycolethers. The activity of ADH is higher in female than in male rat liver. However, it was the same ADH isoenzyme (ADH-3) that oxidized the different glycolethers tested in both male and female rat livers, and the substrate specificity was 2-BE > 2-EE > 2-ME.