Biomedical subjects
Publications and source records attributed to T C Marrs.
The efficacy of dicobalt edetate (Kelocyanor) was compared against that of 4-dimethylaminophenol (DMAP) in experimental cyanide poisoning. DMAP gave better survival. The efficacy has been related to the toxicity of the two compounds.
The single dose oral toxicity of 4- dimethylaminophenol (DMAP) was examined in mice, rats and guinea-pigs and the intravenous toxicity in mice. The oral LD50 in female mice was 946 mg kg-1, in male rats, 780 mg kg-1, in female rats 689 mg kg-1 and in female guinea-pigs 1032 mg kg-1. The intravenous LD50 in female mice was 70 mg kg-1. Dosing with DMAP at the maximum tolerated dose produced Heinz body haemolytic anaemia in rats and Heinz bodies unaccompanied by anaemia in mice. Rats showed biochemical and histological evidence of renal tubular changes.
The acute toxicity of p-aminopropiophenone (PAPP) to three species of laboratory animals has been investigated using solutions in dimethylsulphoxide (DMSO) for intravenous and oral (intragastric) administration. In addition, methaemoglobinaemia and Heinz-body haemolytic anaemia are described.
Rabbits and rats were exposed to single doses of smoke from pyrotechnic mixtures containing red phosphorus. The survivors were observed for up to 14 days. Most of the histological changes observed were found in the respiratory tract and they included abnormalities in the larynx and trachea, alveolitis and, in a few cases, frank pneumonia.
The repeated-dose inhalation toxicity of a smoke containing a mixture of three dyes was tested in female mice, rats and guinea pigs. The green component dye (Solvent Green 3) was retained in the lungs. Particularly in the rats marked collections of alveolar macrophages were found. In the same species several other adverse findings were noted: these included adenocarcinomas of the breast in the high-dose group and a dose-related incidence of biliary hyperplasia. Fatty change was noted in the livers of the test-group mice. A large proportion of the high-dose guinea pigs died during the exposure period, for which reason exposure was stopped early in that group, otherwise the guinea pigs were little affected. However, all test groups of all species showed reductions in growth during the exposure period.
The repeated dose inhalation toxicity of 2-chlorobenzylidene maloninitrile (CS) was investigated in male mice, rats, and guinea-pigs. Exposure was 1 h X day-1 for 120 days surviving animals being killed approximately 1 year after the start of exposure. Excess mortality was noted in the high dose groups of all three species but at exposure concentrations below 30 micrograms X 1(-1) mortality varied little between the control and test groups. Death during the experiment was related to concentration of exposure rather than total dose (Ct). No case of a dose-response relationship between tumours in a particular site, and total dose of CS was noted.
The repeated dose inhalation toxicology of technical grade dibenz-(b.f.)-1,4 oxazepine (CR) was studied in mice and hamsters. The animals were exposed 5 days/week for 18 weeks and retained until 1 year after the start of exposure. CR, at high doses, affected survival of both species, nevertheless the material produced little specific organ-directed toxicity.
Four aminophenones were administered to dogs. Orally p-aminopropiophenone (PAPP) was the most effective methaemoglobin former, while p-aminoheptanoylphenone (PAHpP) was the least effective. p-Aminovalerylphenone (PAVP) and p-aminohexanoylphenone (PAHP) were of intermediate efficacy. With oral PAPP, PAVP and PAHP there was no clear cut relationship between acyl chain length and the timing of peak mean methaemoglobin levels. When PAPP or PAHP were administered intravenously the latter produced lower and later peak methaemoglobin levels than the former.
Rabbits and rats were exposed to single doses of hexachloroethane zinc smoke and observed for up to 14 days. Changes in the respiratory tract included acute inflammation and in some cases necrosis of the laryngeal and tracheal mucosa. Pulmonary oedema and pneumonitis were observed in decedent animals. Animals that survived to the end of the experiment, showed similar but much less florid changes in the respiratory tract.
Explore the source record for details and available documents.
The histopathology of rat lung after exposure to high concentrations of mixed oxides of nitrogen (NOx) has been studied. Considerable damage was observed, which initially took the form of 'thickening' and 'blebbing' of the alveolar epithelium and disruption of type II pneumocytes. These early changes were attributed to the direct effect of the oxidant action of NOx. There then followed a latent period of approximately 6 h after which the development of oedema of the interstitium and alveolar septum was observed. Clinical observations and the results from light and electron microscopical examination suggested that the lung damage caused by exposure to 518 parts/10(6) NOx for 5 min was greater than that caused by 1435 parts/10(6) for 1 min. This was not supported by the findings from light microscopy where similar damage was observed at both dose levels. These results suggest that such exposures might pose a risk of lung damage to man.
The induction of moderate levels of methaemoglobin by 4-dimethylaminophenol (DMAP) was studied in human and dog blood in vitro and in dogs in vivo. Although the rate of formation of methaemoglobin following intravenous injection into dogs was similar to that following addition of DMAP to dog blood in vitro, in the latter case levels fell more slowly. Addition of DMAP at the same concentrations in vitro resulted in more rapid oxidation of haemoglobin and higher peak levels of methaemoglobin in dog blood than in human blood. It was concluded that the rate of formation of methaemoglobin as well as the activity of methaemoglobin reductase must be considered when extrapolating data from the dog to man.
Single oral doses up to 25 mg/kg body weight of methaemoglobin-inducing cyanide antidote, 4-dimethylaminophenol (DMAP) did not result in any gross or histological abnormality in the gastrointestinal tract, liver and kidneys of rats killed up to 24 h after the dose. In animals kept for 7 days after the dose to abnormality was observed in the organs examined or in blood samples taken during the course of the experiment.
Explore the source record for details and available documents.
Dimethylsulphoxide (DMSO) induced swelling in guinea pig ears was found to be abolished by H1- and H2-receptor blocking agents. On histological examination of the ears some degranulation of mast cells was seen. It was concluded that the swelling was mediated by histamine release.
Dibenz (b,f)-1-4 oxazepine (CR) was applied to the skin of C3H and Porton-strain mice, daily for 12 weeks. After a further 80 weeks the animals were sacrificed and examined grossly and histologically. The results were compared with appropriate solvent and untreated controls. No abnormalities were found that could be ascribed to CR, but a high incidence of fatty infiltration of the liver in 1 strain of mice might have been due to the solvent in which CR was dissolved, namely acetone. There were marked differences in the incidence of several lesions in the 2 strains of mice, alveologenic carcinoma being much more common in the Porton mice. CR appeared to have little effect on the skin but both the test and solvent groups of male Porton mice shared an increased incidence of acanthosis.
Explore the source record for details and available documents.