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Biomedical subjects

B A Herbold

Publications and source records attributed to B A Herbold.

10 recordsLinked to original sources
PubMed2000

Investigations on the mutagenicity of 1,4-dichlorobenzene and its main metabolite 2,5-dichlorophenol in vivo and in vitro.

The genotoxic potential of 1,4-dichlorobenzene (1,4-DCB) has been extensively evaluated in vitro and in vivo. The majority of the studies demonstrated the absence of a genotoxic potential for 1, 4-DCB. At variance are a bone marrow micronucleus test (MNT) after intraperitoneal (i.p.) treatment of NMRI mice [Mohtashamipur et al., Mutagenesis 2 (1987) 111-113] and a gene mutation assay on mouse lymphoma cells [McGregor et al., Environ. Mol. Mutagen. 12 (1988) 85-145]. Therefore, we investigated 1,4-DCB and its main metabolite 2,5-dichlorophenol (2,5-DCP) for both endpoints. In an MNT, male and female NMRI mice were treated orally with single doses of 2500mg/kg 1,4-DCB and 1500mg/kg 2,5-DCP, respectively. Smears were prepared 24, 48 and 72h thereafter. No induction of micronuclei was detected for both compounds. Also under the conditions of Mohtashamipur et al. (1987), intraperitoneal treatments of male and female mice with 2 x 177.5 and 2 x 355mg/kg 1,4-DCB failed to induce micronuclei. In addition, CHO/HPRT-gene mutation tests with 1,4-DCB and 2,5-DCP yielded negative results for both compounds with and without metabolic activation system. Therefore, 1,4-DCB and 2,5-DCP are considered to be non-mutagenic in these test systems.

Animals↗
PubMed1997

A new method for the enrichment of single renal proximal tubular cells and their first use in the comet assay.

A protocol was developed to isolate and enrich single renal proximal tubular cells, performing the following steps: in situ kidney perfusion; isolation of renal tissue pieces by collagenase digestion; selective enrichment of proximal tubular fragments by Percoll gradient centrifugation; and isolation of single proximal tubular cells by digestion of proximal tubular fragments with trypsin. The mean enrichment rate, determined by the glucose-6-phosphatase staining method, was 78.9% with a mean cell viability of 93.8%. After modification of the comet assay protocol, genotoxicity in proximal tubular cells could be investigated. A dose-dependent genotoxic effect of ethyl methanesulphonate in these cells was proven.

Animals↗
PubMed1992

Review of the mutagenicity/genotoxicity of butylated hydroxytoluene.

Butylated hydroxytoluene (BHT) is an effective, widely used, low cost antioxidant. A host of studies examining the potential of BHT to cause point mutations have been published. They include in vitro studies on various bacterial species and strains and on various types of mammalian cell lines as well as in vivo studies on Drosophila melanogaster, silk worms and also the mouse specific locus test (involving long-term exposure). Together these studies convincingly show the absence of a potential for BHT to cause point mutations. A great number of studies on many cell types and species have also been carried out to examine the potential of BHT to cause chromosome aberrations. In vitro studies have been published using plant cells and the WI-38, CHL, CHO, and V79 mammalian cell lines. In vivo studies have been carried out on somatic and/or germ cells of Drosophila melanogaster, rats and mice. Nearly all studies, especially those using validated test systems, indicate that BHT lacks clastogenic potential. In vitro studies on bacterial, yeast and various mammalian cell lines including DON, CHO, CHL cells and primary hepatocytes demonstrate the absence of interactions with or damage to DNA. Taking all the existing data into account, the weight of evidence suggests that BHT does not represent a relevant mutagenic/genotoxic risk to man.

Animals↗
PubMed1988

Assessment of the potential germ cell mutagenicity of industrial and plant protection chemicals as part of an integrated study of genotoxicity in vitro and in vivo.

An approach is described that enables the germ cell mutagenicity of chemicals to be assessed as part of an integrated assessment of genotoxic potential. It is recommended, first, that the genotoxicity of a chemical be defined by appropriate studies in vitro. This should involve use of the Salmonella mutation assay and an assay for the induction of chromosomal aberrations, but supplementary assays may be indicated in specific instances. If negative results are obtained from these 2 tests there is no need for the conduct of additional tests. Agents considered to be genotoxic in vitro should then be assessed for genotoxicity to rodents. This will usually involve the conduct of a bone marrow cytogenetic assay, and in the case of negative results, a genotoxicity test in an independent tissue. Agents found to be non-genotoxic in vivo are regarded as having no potential for germ cell mutagenicity. Agents found to be genotoxic in vivo may either be assumed to have potential as germ cell mutagens, or their status in this respect may be defined by appropriate germ cell mutagenicity studies. The basis of the approach, which is supported by the available experimental data, is that germ cell mutagens will be evident as somatic cell genotoxins in vivo, and that these will be detected as genotoxins in vitro given appropriate experimentation. The conduct of appropriate and adequate studies is suggested to be of more value than the conduct of a rigid set of prescribed tests.

Animals↗
PubMed1983

Criteria for the standardization of Salmonella mutagenicity tests: results of a collaborative study. II. Studies to investigate the effect of bacterial liquid culture preparation conditions on Salmonella mutagenicity test results.

The influence of various parameters and growth conditions in the "overnight culture" of Salmonella typhimurium strains on mutagenicity test results was investigated. A number of factors were first suspected to be of some importance for the quantitative outcome of the mutagenicity test. None of them, however, was found to influence the results to such a marked extent as to be a major source of variability. Only the brand of nutrient broth used for the propagation of the bacteria proved finally to have a certain effect on the number of (spontaneous and induced) revertant colonies, although no precise and quantitative statements can be made with regard to a possible standardization of this experimental segment in the Salmonella mutagenicity test. The occurrence of such unpredictable but noticeable influences is, however, evidence for the importance of an intralaboratory optimization and standardization of all parts of the test procedure.

Animals↗
PubMed1982

Mutagenicity studies with 2,4,5-T on bacteria and mammalian germ cells.

The herbicide 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) was evaluated for potential mutagenicity by a Salmonella/mammalian-microsome test, a dominant lethal test on female rats, and by a cytogenetic assay on spermatogonia of Chinese hamster. In the Salmonella/mammalian-microsome test on four Salmonella typhimurium strains (TA 1535, TA 100, TA 1537, and TA 98), doses of up to and including 2500 micrograms/plate did not cause any mutagenic effects. In a dominant lethal test on female rats, 8-week dietary administration of 2,4,5-T at doses of up to and including 10 mg/kg/day did not cause any increase in preimplantation loss or the rate of dead implants, and did not have any effect on the fertilization quota. Cytogenetic analysis of the spermatogonia of male Chinese hamsters orally dosed five times at 24-hr intervals with 2,4,5-T at levels of up to and including 100 mg/kg did not provide any indication of 2,4,5-T having chromosome-damaging effects. Therefore, none of the three test systems provided any indication of 2,4,5-T having a mutagenic effect.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1981

Studies to evaluate artificial sweeteners, especially Remsen--Fahlberg saccharin, and their possible impurities, for potential mutagenicity by the Salmonella/mammalian liver microsome test.

Cyclamate, cyclohexylamine, saccharin, boiled saccharin, 3 organic extracts of this sweetener and 9 possible impurities, including OTS and PTS, were evaluated for potential mutagenic activity by the Salmonella/mammalian liver microsome test on Salmonella typhimurium TA1535, TA100, TA1537 and TA98 (extracts only on TA98) with doses up to at least 2500 micrograms per plate with and without metabolic activation. No mutagenic activity was established either for cyclamate, cyclohexylamine or saccharin, or for some of the possible impurities of saccharin synthesized by the Remsen--Fahlberg or Maumee process. Only 1 organic extract gave inconclusive results in 3 consecutive experiments. No mutagenic activity was noted for saccharin refluxed for 2 h in solution.

Animals↗