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Biomedical subjects

L Machemer

Publications and source records attributed to L Machemer.

36 records · Page 2Linked to original sources
PubMed1975

Studies of embryo toxicity in rats and rabbits.

Embryo toxicity studies were carried out to investigate the effects of different doses of fluorescent whitening agents (FWAs) after oral administration to pregnant rats from the 6th to the 15th day of pregnancy and to rabbits from the 6th to the 18the day of pregnancy. In own studies two FWAs of the bis(triazinylamino or triazoly)stilbenedisulfonic acid type showed no embryo-toxic or teratogenic effect on wither species at daily doses up to 1000 mg/kg. Also the toxic dose to the mothers, 3000 mg/kg, given to rabbits in case of one FWA was without these effects. In the studies of KEPLINGER, et al. (Toxicol. Appl. Parmacol. 27: 494-506, 1974) a triazolylstilbenemonosulfonic acid derivative, two bis(triazinylamino)stilbenedisulfonic acid derivatives and a bis(sulfostyryl)diphenyl derivative had no terato-enic effect on rabbits when administered orally in doses of up to 30 mg/kg/day.

Animals↗
PubMed1975

Testing mutagenic properties with the dominant lethal test on the male mouse.

Mytagecity studies were carried out with fluorescent whitening agents (FWAs) using the dominant lethal test on male mice. Own tests with five FWAs, and those of KEPLINGER, et al. (Toxicol. Appl. Pharmacol.27: 494-506, 1974), with four FWAs, are described. In our tests, acute oral administration of five FWAs at a dose of 5000 mg/kg body weight gave no evidence of a mutagenic effect during 8 weeks' mating. The FWAs used were three bis(triazinylamino)stilbenedisulfonic acid derivatives and a 1,3-diphenyl-2-pyrazoline derivative. The results of the tests carried out by KEPLINGER, et al. showed that intraperitoneal injection of the four FWAs produced no mutagenic effect during six weeks' mating; the whiteners used were a triazolylstilbenemonosulfonic acid derivative (50 mg/kg), two bis(triazinylamino)stilbenedisulfonic acid derivatives (50 mg/kg) and a bis(sulfostyryl)biphenyl derivative (10 mg/kg).

Animals↗
PubMed1975

[Influence of several weeks' treatment of male and female mice with saccharin, cyclamate or cyclohexylamine sulfate on fertility and dominant lethal effects (author's transl)].

The purpose of this investigation was to find out whether long-term treatment of male and female mice with saccharin sodium, sodium cyclamate or cyclohexylamine sulfate, would reduce fertility or induce dominant lethal mutations. Before mating, saccharin sodium or sodium cyclamate were added to the food in a concentration of 1%, while cyclohexylamine sulfate was added in a concentration of 0.11% for at least 10 weeks. This treatment corresponded, in the case of saccharin sodium and sodium cyclamate, to an active substance intake of approx. 2000 mg/kg per day and for cyclohexylamine sulfate to an intake of approx. 200 mg/kg per day (corresponding to approx. 136 mg cyclohexylamine per kilogram per day). These doses affected neither the females nor the males in respect of appearance, behaviour, and weight gain. The doses were also compatible with the normal fertility of the animals. Furthermore, in all cases the treatment did not cause a biologically important increase of pre-implantative and post-implantative losses. The dominant lethal tests did not indicate a mutagenic action of saccharin sodium or sodium cyclamate (1% in the food) and of cyclohexylamine sulfate (0.11% in the food) after 10 weeks' treatment of male and female mice. These results, obtained after long-term treatment, corresponded generally to the findin

Animals↗
PubMed1975

Experiences with the dominant lethal test in female mice: effects of alkylating agents and artificial sweeteners on pre-ovulatory oocyte stages.

Pre-ovulatory oocytes are especially sensitive to mutagenic influences. Since post-dictyotene oocytes are not subject to selection and elimination before fertilization, they may reveal mutagenic effects directly and unrestrictedly. Presuming that a chemical is administered at pro-estrus to female mice one can conclude that the substance or its active metabolite has the chance to reach the gamete during the sensitive pre-fertilization stages. We proved the usefulness of the test system by investigating the effects of alkylating agents. A second step was to investigate other substances. The following treatments induced dominant lethal effects: methyl methanesulfonate 100 mg/kg i.m., cyclophosphamide 200 mg/kg per os, triaziquone 0.25 mg/kg i.p. In contrast, the following agents were ineffective and can be classified as not mutagenic in this method: sodium cyclamate 10 000 mg/kg per os, saccharine sodium, 10 000 mg/kg per os, cyclohexamine sulfate 150 mg/kg per os, ethanol 5 ml/kg per os.

Animals↗
PubMed1975

Method for testing mutagenic effects of chemicals on spermatogonia of the Chinese hamster: results obtained with cyclophosphamide, saccharin, and cyclamate.

The action of different cyclophosphamide doses on spermatogonia of the Chinese hamster was examined. Two oral treatments at an interval of 24 h were carried out and spermatogonia were prepared for examination 24 or 48 h after the second dose. Accordingly the effects of 5 oral cyclophosphamide doses given on five consecutive days were tested on spermatogonia and preparations were made 24 or 72 h after the last treatment. The results so obtained form the basis of reference for findings following oral administration of saccharin sodium, sodium cyclamate, or trimethylphosphate. Male Chinese hamsters, 6-8 per group, were used, from each of which about 100 metaphases were evaluated. Preparation was carried out essentially according to Hoo and Bowles [Mutation Res. 13, 85-88 (1971)]. gaps, breaks, fragments, deletions and translocations were rated as structural aberrations. For every dose and every time of preparation the incidence of metaphases with aberrations, with or without gaps, and with translocations were assessed. The different experiments led to the following conclusions: 1. By analysis of spermatogonial metaphases of treated Chinese hamsters chemically induced chromosome aberrations can be proved with certainty. 2. Incidence of metaphases with translocations is a sensitive measure which is distinctly superior to the summary determination of all aberrations. In this way it was possible to show a mutagenic influence of 2 times 8 mg/kg cyclophosphamide p.o. 3. Following two cyclophosphamide doses administered at an interval of 24 h it was found that preparations of spermatogonia 48 h after the second dose was better suited for the evaluation than that at 24 h, for aberrations were more frequent with the same treatment. After five cyclophosphamide treatments at 24-h intervals, aberrations were somewhat more frequent 24 h after the last dose than at 72 h; in any case the values exceeded significantly the results of untreated controls. 4. A conclusive numeric chromosome analysis is not possible with the spermatogonia test, since a relatively high percentage of non-diploid cells is apparently of methodological origin. 5. Tests with 2 times 500 or 5 times 1000 mg/kg trimethylphosphate orally showed an increase in chromosome aberrations compared with controls indicating mutagenic effects in both cases; with 5 times 1000 mg/kg p.o., however, the figures were low as a result of marked mitotic inhibition. 6. The results of the spermatogonia test on Chinese hamsters revealed no mutagenic effects of saccharin sodium 2 times 5000 mg/kg orally, and of sodium cyclamate 5 times 2000 mg/kg orally. This is based on comparisons of the results both with untreated controls and positive controls treated with trimethylphosphate or cyclophosphamide.

Animals↗
PubMedDate not supplied

Adequacy of required regulatory hazard testing for the detection of potential hormonal activity of crop protection chemicals.

The capacity of some synthetic chemicals, the so-called "endocrine-disrupting chemical," to alter hormonal activity, as well as the adequacy of the testing of chemicals to evaluate this capacity, has been called into question. Among the chemicals indicted have been certain crop protection agents or pesticides. Crop protection chemicals rank among the most closely regulated and thoroughly tested chemicals in use in both the human health and environmental hazard areas. However, it has been proposed that in vitro and in vivo screening tests be used to identify potential endocrine-active chemicals and to supplement or replace required regulatory bioassays. In vitro tests, such as receptor binding, examine a single chemical event, do not measure toxicity, post-receptor-mediated biological response, or the absorption, distribution, metabolism, and elimination of a chemical. Therefore, data derived solely from such a limited testing technique should not be used as a basis for selection of chemicals for making regulatory decisions. In vivo screening tests, such as the uterotrophic assay, which promise to provide a rapid answer to a targeted question, do not capture the complexity of the biological response. As in the case with in vitro tests, results from a single in vivo test, such as a change in uterine weight, should not be used as a basis for regulatory decision making. Further, it has been suggested that such a screening battery should be put into place for ecotoxicity testing. Yet it is well recognized that endocrine-active chemicals that affect fish and wildlife in their natural habitat have been shown to cause similar adverse effects in laboratory test animals. Therefore, these screening tests do not add value to the current regulatory test battery. Evidence is presented that demonstrates that the regulatory safety assessment paradigm has a low likelihood of missing potential endocrine-active chemicals and has served society well.

Animals↗