Recent state of lindane metabolism.
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Biomedical subjects
Publications and source records attributed to R Engst.
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Investigations on the relationship of the environmental contamination with cancer are shown to be necessary. Epidemiologic investigations point to a connection of the increased occurence of cancer in the gastro-intestinal tract with dietetic factors. The high cancer rate in the gastro-intestinal tract (amongst other factors) is discussed as a result of the uptake of exogenic foreign matterns with the food. The possibilities of the contamination by cancerogenic compounds are summarized. The necessity of international co-operation in the field of finding out, as far as possible, sources and degree of food contamination by cancerogenic compounds is motivated beginning with polycyclic aromatic compounds, whereby at present benzo-(a)-pyrene comes into question as a reference substance. The laying down of controllable hygienic norms as preliminarily tolerable limits in the proper sense of an unavoidable dose are discussed. They could be a basis of oncological preventive measures (minimization or elimination of cancerogenic compounds in foods).
The causes of hexachlorobenzene (HCB) contamination of the environment are of complex nature. Besides the microbial metabolism of lindane to HCB, the pyrolysis of pentachlorophenol (wood impregnation), the chlorine treatment of lignin-containing lyes and possible contaminations with active agents which are industrially synthetized from polychlorbenzenes must be regarded as causes being in part still hypothetical.
The described method enables a simultaneous identification and determination of aflatoxin M1 and B1 in milk and dairy products by means of a self-registering fluorescence spectrophotometer with a thin-layer chromatographic accessory, directly from the plate. The semiquantitative estimation on the thin-layer chromatographic plate enables also routine analyses in the hygienic practice. The recovery rates for aflatoxin M1 and B1 in milk are about 83 and 82%, respectively -- the detection limit is about 0.1 microng per kg. The recovery rates for aflatoxin M1 and B1 in milk powder are about 89 and 94%, respectively -- the detection limit is bout 0.5 microng per kg. The reproducibility is given with a standard deviation between +/- 1.1 and 6,3% and a variation coeffecient of 1.3 and 6.7, respectively. 4 of 24 analized samples of commercial winter milk were aflatoxin M1-positive, whereas aflatoxin B1 could not be found. One of the milk powder products, a sample of the infant food, "Ki-Na", made in the GDR, contained, however aflatoxin B1. Aflatoxin M1 could not be found. Food-hygienic-toxicological conclusions are discussed.
A report is made on 80 male patients aged 19-25 and suffering from common acne, who were treated with vitamin A acid (Eudyna) partly as inpatients and partly as outpatients. All stages were present from acne comedonica to acne conglobata. The preparation was available in the form of cream and jelly, each containing 0.05% tretinoin. As a rule, the drug was applied once daily. At the end of the tretinoin treatment lasting for a maximum of 9 weeks, a decrease in comedones of more than 90% is reported. The tolerance of Eudyna was seen to be good to very good in more than two thirds of the patients.
Almost 55% of lindane (gamma-HCH) which had been applied in vitro are removed by simple hexane extraction of the blood; if blood fractions are extracted, a total rate of 95% results. The partition of gamma-HCH between the plasma and the erythrocytes is approximately I:I; when HCH erythrocytes are incubated in fresh plasma, almost 60% of erythrocyte HCH pass into the plasma. The erythrocytes absorb nearly 90% of the HCH contained in an aqueous medium. Haemolysis showed that HCH is most probably transferred through the membrane. The partition of HCH between the cytoplasm and the membrane fraction ranges from 3:7 to 7:3. TCA precipitates almost 90% of erythrocyte HCH together with the protein. The absorbing capacity of the erythrocytes could be followed up to nearly 0.4-10(-6)M/ml of blood. Cadmium increases, lead decreases the binding of HCH to the erythrocytes; mercury and ethanol exert but small effects.
The gas chromatographic analysis of the daily diets (without beverages) of men consuming at maximum 4000 kcal per day, in spring, summer and autumn 1971, revealed always residues of chlorinated hydrocarbons. With an average food amount of 1635 g per day, each subject (having an average body weight of 65 kg) ingested 105 mug of DDT, 20 mug of DDE, 20 mug of DDD, and 149 mug of total DDT and 10 mug of lindane, respectively. The contamination was inferior to the ADI values recommended by the WHO/FAO. From winter 1971 to autumn 1972, the authors also analysed the daily diets (including beverages) of 1-3-year-old children (having an average body weight of 12 kg) in a week-nursery. The average food amount of 1230 g per day contained 42 mug of DDT, 12 mug of DDE, 8 mug of DDD, and 64 mug of total DDT and 7 mug of lindane, respectively. From these values a total DDT intake of 5.3 mug/kg of body weight was calculated which exceeds the ADI value for adults. The claim for a zero tolerance for victuals and ready-to-use baby foods is corroborated. Consequently the complete replacement of DDT by other insecticides is a measure which is imperative not only from the viewpoint of prophylaxis but also from that of health policy.
Using the previously described test method, the authors studied with the aid of iodine-131 labelled NaI the effects of daily doses of 30 and 75 mg DDT/kg of body weight, and of 12 and 36 mg of lindane/kg of body weight on the iodine and hormone metabolism in the rat. With DDT, the authors observed a marked increase of the thyroid mass and of the thyroid tri-iodothyronine and thyroxin levels and a simultaneous decrease of the thyroid iodine level. The values for serum iodine and protein-bound iodine were reduced. Serum thyroxin was slightly increased. Serum tri-iodothyronine was markedly increased, which was also true of the iodine fractions in the liver. Lindane was considerably less effective. Only the decrease of thyroid tri-iodothyronine and the simultaneous increase of thyroid thyroxin were striking. In the serum, both hormones remained unchanged. The values for the urine fractions of both the active principles were indicative of a hypofunction. The causes of the changes observed were discussed with regard to the findings of other authors. The present results permit the conclusion that the effects of the pesticides tested are obviously complex by nature.
The authors describe a method for the determination of byssochlamic acid in fruit juice. After extraction and purification, byssochlamic acid is separated by thin-layer chromatography on HF 254 silica gel. The quenching of fluorescence of byssochlamic acid is estimated quantitatively on the plate by means of the thin-layer attachment of a fluorescence spectrophotometer using reference substances. For fruit juices the recovery rate is 80%; the limit of detection lies at 0.5 p.p.m. Byssochlamic acid could not be detected in commercially-available fruit juice and neither in juices produced of fruits which had spontaneously got mouldy.
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The metabolism of lindane and its metabolites, gamma-PCCH, PCB, and PCP, has been studied in rats. Urine, faeces, blood and important organs were analyzed for free metabolities and those bound as beta-glucuronides. TeCCOL was identified as a main metabolite by GC/MS and gamma-PCCH has been evaluated toxicologically. A degradation scheme, based on experimental results and comprising only one hypothetical metabolite is proposed and discussed.
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The metabolism of 14C-lindane, its short-lived main metabolite gamma-2,3,4,5,6-pentachlorocyclogexene and penta-/hexachlorobenzene was followed in a mould culture after 6, 17, 30 and 52 days. The distribution in the culture medium was also investigated.
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Hexachlorobenzene is but slowly metabolized by a lindane-decomposing mould culture, only pentachlorobenzene being detected as a metabolite. The degradation of pentachlorobenzene yields the following metabolites: pentachlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,4,6-tetrachlorophenol, 1,2,3,4-tetrachlorobenzene, 1,2,4,5- and/or 1,2,3,5-tetrachlorobenzene, 2,3,4-trichlorophenol, 2,4,6-trichlorophenol, 3,4,5-trichlorophenol, 1,3,5-trichlorobenzene. The establishment of a degradation pattern is under way.
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