EDITORIAL

Copyright

Rudolf Wittenzellner (1921-1997)

Copyright 1997 Academic Press

Disposition and metabolism of 1-nitropropane in rats and chimpanzees.

The metabolic fate of 1-nitropropane (1-NP) has not been previously reported. In this study male rats and chimpanzees were given single doses of 40 mg/kg ip and 5 mg/kg iv 1-[1-14C]NP, respectively. The quantitative extent of urinary and fecal elimination was similar in both species. The rats excreted 16.5% of the dose in urine and 1.7% in feces. For chimpanzees the respective values were 14.8 and 1.2%. Experiments with rats demonstrated that the major route of elimination was by exhalation. With a total elimination via the lungs of 72.6%, rats expired 10.3% of the dose as unchanged 1-NP. Five polar metabolites were isolated from the urine of chimpanzees. The two major metabolites were identified as 3-hydroxypropionic acid and N-methyl-N-2-(methylsulfinyl)ethylpropionic acid amide (NMPA). Both substances were also excreted in rat urine. The two identified metabolites indicate that 1-NP was degraded to propionic acid, part of which was modified to 3-hydroxypropionic acid or NMPA. A hypothetical pathway for the biochemical generation of NMPA is suggested.

From single-substance evaluation to ecological process concept: the dilemma of processing gold with cyanide.

In the past decades, limit concentration values for environmentally dangerous synthetic and natural chemical substances have been established in industrialized countries. Depending on the range of application, state of aggregation, propagation velocity, specific action on living organisms, long- or short-time effect, etc., different terms are used to specify these limit concentrations (acceptable daily intakes, TLV, LD50, emission values, water quality standards, etc.). Several parameters (e.g., range of application, ethic and social valuation, environmental factors, scientific knowledge) have led to nationally and internationally varying values depending on the region and time. The accuracy of this system of evaluation cannot necessarily be improved by listing further analytical data, but rather by furnishing sufficiently secured scientific data for a serious discussion, with the public concepts influenced more and more by the mass media. The best-established scientific knowledge has been acquired by the chemical industry. National and international groups demand that ecological-chemical problems in other fields of industry be dealt with as well; this research should, without doubt, be intensified. The example of the mining industry, which must employ chemical methods to isolate small concentrations (ppm), demonstrates the environmental conflict caused by the increasing world population, requiring the adaptation of the process by industry to the modern environmental concept. This is illustrated by the evolution of the gold recovery process.

Impaired renal function in diabetic chimpanzees (Pan troglodytes).

Studies were conducted to assess the renal functional state in two recently discovered diabetic chimpanzees. Both were nonobese, adult female animals with the non-insulin-dependent form of impaired glucose tolerance, analogous to the Type II or nonobese, maturity-onset diabetes of humans. Both animals displayed moderate-to-heavy proteinuria and glycosuria in response to intravenous administration of glucose or tolbutamide. Chimpanzee number 333, but not number 1037, had fasting proteinuria and chronic hypertension. Renal function studies, using the inulin clearance method, demonstrated significantly decreased glomerular filtration rates and elevated rates of sodium excretion for both animals. The rate of chloride excretion was also elevated in animal number 1037, but potassium excretion was apparently unaffected in both animals. Abnormal serum biochemical parameters demonstrated for chimpanzee number 333 included elevations in calcium, magnesium, creatinine, urea nitrogen, and uric acid; animal number 1037 had only an elevated serum creatinine. Results are consistent with the occurrence of renal disease similar to the nephropathy that develops in human diabetics. The difference in severity of renal impairment in the two chimpanzees is possibly related to differences in duration and severity of impaired glucose tolerance. A progression of both diabetic and renal disorders is most probable.

The cyanide leaching gold recovery process is a nonsustainable technology with unacceptable impacts on ecosystems and humans: the disaster in Romania.

The statements and discussions in this commentary are based on the disastrous situation near Baia Mare in Romania, where a dam of a cyanide basin burst on January 30, 2000, with serious consequences.

Epidemiological studies related to the use of hormonal agents in animal production.

The principal types of hormonal agents used in the production of meat for human consumption are estrogens, progestagens, and androgens. Only the last class is truly anabolic. Each type of compound named above has fairly characteristic toxic effects after prolonged intake. In this review, an attempt will be made to relate available information from experience with the administration of these three types of hormones to humans to the question whether sufficient amounts of these chemicals can remain in meat cut from carcasses of animals administered hormones during finishing to have deletarious effects on human ingesters. Present indications are that administration of stilbestrol to pregnant women may result in a somewhat increased incidence of cervical and vaginal cancers in their daughters; such administration appears to have no effect on the incidence of cancers in sons and only slight, if any, effect on that in the mothers. Other estrogens seem to have no specific effects on the incidence of cancer. Progestagens also are not known to induce any specific lesions. Although many androgens are known to produce edema, fever, and jaundice, they have not been found to cause specific lesions to any significant extent. With reference to stilbestrol, the doses given to the mothers of affected children have ranged between 5 and 125 mg/day. Because muscle, liver, and kidney from steers treated with stilbestrol in the usual way (s. c. implantation of a pellet at the base of an ear) have been found to contain less than 0.5 ppb of stilbestrol one month after implantation of the pellet, it is obvious that, to approach even the lowest clinically used dose of stilbestrol, a person would have to eat daily a quantity of such animal products that would be impossible to ingest. The findings that a mean of 26.4% of an oral dose of stilbestrol is excreted within 24 hours and that 99.5% is excreted within a week indicate that cumulation of this chemical within the body from the low level of intake provided by meats is not likely to reach a significant level. This would be so even though the animal product contained more than the 0.5 ppb mentioned above.

Safety assessment based on irrelevant toxicologic data: an extraordinary case of bromomethane used as a fumigant.

Bromomethane (BM) is a fumigant used in agriculture; it readily breaks down to bromide ion. WHO assessed the ADI of BM, at 1 mg/kg, using data on the toxicity of bromide. On the other hand, U.S. EPA used the observation of hyperplasia in the forestomach of rats given BM by gavage and arrived at a value of 0.0014 mg/kg. The validity of EPA's assessment is thus subject to question because of the data involved by (1) direct introduction of this volatile and reactive chemical to the GI by gavage and (2) using lesions in the rat forestomach which is absent in humans.