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Biomedical subjects

T C Marrs

Publications and source records attributed to T C Marrs.

At least 37 records · Page 2Linked to original sources
PubMed1989

The biochemical and pathological changes produced by the intratracheal instillation of certain components of zinc-hexachloroethane smoke.

Zinc chloride which is formed by igniting a mixture of zinc oxide and hexachloroethane in the production of white smokes has been shown to produce oedema when given to rats as a single instillation. The oedematous reaction, as assessed by histopathology and measurements of alveolar surface protein in lavage fluid, is variable, dose-dependent, and maximal at 3 days but at sub-lethal doses it regresses after 7 days. The parent compound, zinc oxide, does not produce these effects. In some animals there is evidence of a fibrogenic response at 7 days post-exposure although it is currently unknown whether or not this effect is progressive.

Animals↗
PubMed1989

Methaemoglobin production and reduction by methylene blue and the interaction of methylene blue with sodium nitrite in vivo.

Methylene blue, at high concentrations, interferes with the estimation of methaemoglobin using the IL 282 CO-oximeter: the dye does not interfere with the method of Evelyn & Malloy for determination of methaemoglobin. In beagle bitches methylene blue causes both methaemoglobinogenesis and methaemoglobin reduction, the effect of the former being to delay the decline of methaemoglobin levels, when methylene blue is used to reverse the methaemoglobinaemia produced by sodium nitrite.

Animals↗
PubMed1988

The repeated dose toxicity of a zinc oxide/hexachloroethane smoke.

Mice, rats and guinea pigs were exposed to the smoke produced by ignition of a zinc oxide/hexachloroethane pyrotechnic composition, 1 h/day, 5 days/week, at three different dose levels, together with controls. The animals received 100 exposures except for the high dose guinea pigs, which underwent 15 exposures, because of high death rate during the first few days of exposure. The test material had very little effect on weight gain, but there was a high rate of early deaths in the top dose of mice. A variety of incidental findings was seen in both decedents and survivors, but organ specific toxicity was, with one exception, confined to the respiratory tract. The most important of these findings was a statistically significant increase in the frequency of alveologenic carcinoma in the high dose group mice (p less than 0.01) and a statistically significant trend in the prevalence of the same tumour over all dose groups and the controls. A variety of inflammatory changes was seen in the lungs of all species and some appeared to be treatment-related. Fatty change in the mouse liver was more common in the middle and high dose groups than the controls. The aetiology of the tumour incidence is discussed and it is pointed out that hexachloroethane and zinc, as well as carbon tetrachloride, which may be present in the smoke, may be animal carcinogens in appropriate circumstances. Carbon tetrachloride is a known human carcinogen.

Animals↗
PubMed1988

An investigation of possible models for the production of progressive pulmonary fibrosis in the rat. The effects of repeated intratracheal instillation of bleomycin.

Pulmonary fibrosis is a common later sequel to damage to the lung caused by a wide variety of agents. Bleomycin is an antineoplastic drug used in the treatment of squamous cell carcinomas and lymphomas. It is known to cause pulmonary fibrosis is both man and experimental animals. Bleomycin, dissolved in saline, was given by intratracheal instillation (dose = 0.5 U/animal; dose vol. = 0.5 ml/animal) to groups of at least 5 rats. Groups received either a single dose or 2, 3 or 4 doses each given a week apart. They were then sacrificed at periods of up to 90 days after the last dose. Subsequent histology revealed varying degrees of alveolitis, type II pneumocyte hyperplasia, alterations to alveolar structure including obliteration, degeneration, collapse and enlargement with significant interstitial fibrosis. The lesion appeared to be diffusely distributed throughout the lung. After a single dose or 2 doses regression of the lesion was observed with time following dosing whereas with 3 or 4 doses of bleomycin the changes increased progressively in extent and severity. Three or more doses of intratracheal instilled bleomycin appear to be a good model of progressive pulmonary fibrosis in the rat.

Animals↗
PubMed1988

Comparative acute systemic toxicity of sodium arsenite and dichloro(2-chlorovinyl)arsine in rabbits.

The acute intravenous toxicity of sodium arsenite and dichloro(2-chlorovinyl)arsine (lewisite) has been compared in rabbits to provide a quantitative and qualitative model for future assessment of treatments of lewisite poisoning. The LD50 of sodium arsenite was 7.6 mg.kg-1; that for lewisite was 1.8 mg.kg-1. On the basis of arsenic content the former was 6.5 times less toxic than the latter. Significant differences in tissue arsenic content and pathology were found between the 2 materials. Histologically, changes were observed in the lungs and gall bladder after lewisite injection but not after sodium arsenite. It was concluded that use of sodium arsenite is not a suitable substitute model for lewisite poisoning.

Animals↗
PubMed1988

Pharmacokinetics of intravenous potassium cyanide.

The pharmacokinetics of intravenously injected potassium cyanide have been studied in Beagle bitches. In the period up to about 80 min after dosing, blood levels fell in a manner consistent with first-order elimination kinetics. Thereafter blood cyanide concentrations fell at a slower rate, indicating that a second phase of slower elimination had been entered.

Animals↗
PubMed1987

Acute toxicity of T2 toxin in rats, mice, guinea pigs, and pigeons.

The acute intravenous, intragastric, subcutaneous, intraperitoneal and intratracheal toxicity of T2 toxin has been studied in rats, mice, guinea-pigs, and pigeons. The acute LD50 values obtained varied between 1.0 and 14 mg X kg-1, there being little difference between the various routes in any given species. T2 caused vomiting in pigeons at doses of one fifth or less the LD50. In rats doses of 3.0 and 5.0 mg X kg-1 T2 produced lymphopenia, reticulocytosis, and in the highest dose groups normoblastaemia. Additionally, changes in plasma alkaline phosphatase and aspartate aminotransferase activities were seen. Histological changes were observed in lymphoid organs and were most severe in the thymus, lymph nodes, and Peyer's patches. The spleen was less severely affected. Gastrointestinal changes consisting of dead and dying lymphoid cells throughout the lamina propria were seen together with, in some cases, mucosal ulceration. The time course of the development and of the reversal of the changes was followed.

Administration, Oral↗
PubMed1987

Species differences in methaemoglobin production after addition of 4-dimethylaminophenol, a cyanide antidote, to blood in vitro: a comparative study.

Methaemoglobin production after addition of DMAP to blood of various species, has been studied in vitro. The study was undertaken both with blood, as taken, and after equilibration with atmospheric oxygen. Considerable interspecies variation in methaemoglobin production was found. When the initial rate of methaemoglobin formation was considered only marmoset and human blood showed any marked degree of inhibition by equilibration with atmospheric oxygen.

Aminophenols↗
PubMed1987

Interspecies differences in rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) activity in liver, kidney and plasma.

Rhodanese levels have been measured in liver, kidney and plasma from a number of species. Liver activity was low in marmosets, pigeons and beagle bitches. Levels were high in rats and somewhat lower in hamsters and guinea pigs while levels in two strains of rabbits were intermediate between guinea pigs and marmosets. The relationship between hepatic and plasma rhodanese and cyanide sensitivity is discussed.

Animals↗
PubMed1987

Methemoglobinogenic potential of primaquine and its mutagenicity in the Ames test.

Single doses of primaquine did not produce methemoglobinemia in beagle bitches. Repeated daily administration for 12 days produced a gradually rising level of methemoglobin over that time period, unaccompanied by depletion of erythrocytic reduced glutathione. Primaquine was mutagenic in the Ames test in Salmonella typhimurium strain TA 1537, with or without S9, using a liquid preincubation assay. Primaquine was non-mutagenic in this assay to strains TA 1535, TA 1538, TA 98 and TA 100, regardless of the presence or absence of S9. In the standard overpour Ames test, the drug was non-mutagenic in all 5 Salmonella strains, both with and without S9 metabolic activation.

Animals↗
PubMed1987

Effect on blood and plasma cyanide levels and on methaemoglobin levels of cyanide administered with and without previous protection using PAPP.

Hydrogen cyanide was administered intravenously at doses of 0.67 or 1.34 mg kg-1 to beagle bitches after protection with oral p-aminopropiophenone (0.5 mg kg-1). Hydrogen cyanide was also administered to unprotected bitches at the lower level (0.67 mg kg-1) only. PAPP protection caused sequestration of cyanide inside the red cells. In the case of the lower dose of cyanide this resulted in a lower plasma cyanide in protected than unprotected bitches. In the case of the higher dose it resulted in survival, despite 1.34 mg kg-1 being a known lethal dose. It is concluded that prior administration of PAPP ameliorated the effects of cyanide poisoning.

Animals↗
PubMed1987

Sex differences in the production of methaemoglobinaemia by 4-aminopropiophenone.

A methaemoglobin former, 4-aminopropiophenone (p-aminopropiophenone, PAPP), which is active only after metabolic activation in vivo, exhibits a sex difference in male Beagle dogs and bitches. Bitches produced more methaemoglobin for a given dose of PAPP than male dogs. The probable reason for this difference was a lower rate of N-hydroxylation in male dogs.

Animals↗
PubMed1986

Kinetics of methaemoglobin production. (1). Kinetics of methaemoglobinaemia induced by the cyanide antidotes, p-aminopropiophenone, p-hydroxyaminopropiophenone or p-dimethylaminophenol after intravenous administration.

Methaemoglobin profiles have been studied by using ISIS, a simulation package, and NONLIN, a non-linear least-squares analysis regression program. A simple kinetic model which satisfactorily describes methaemoglobin profiles after p-aminopropiophenone (PAPP) administration and 4-dimethylaminophenol (DMAP) administration has been developed. The two compounds differed mainly in their effective rates of elimination. The model less satisfactorily described methaemoglobin profiles after p-hydroxyaminopropiophenone (PHAPP) administration.

Aminophenols↗
PubMed1986

Kinetics of methaemoglobin production. (2). Kinetics of the cyanide antidote p-aminopropiophenone during oral administration.

The kinetics of methaemoglobin production by orally administered p-aminopropiophenone (PAPP) was studied by using a kinetic model previously developed to describe methaemoglobinaemia consequent on intravenous injection of PAPP. Both ISIS, a simulation package, and NONLIN, a non-linear least-squares regression analysis program, were used to analyse the data. Some modification of the model was necessary to describe oral profiles and 40-50% of the administered PAPP appeared to be being metabolized at first pass to a non-active metabolite.

Administration, Oral↗
PubMed1986

Acute toxicity of T2 mycotoxin to the guinea-pig by inhalation and subcutaneous routes.

The acute inhalation and subcutaneous toxicity of T2 mycotoxin has been investigated in guinea-pigs. The toxicity by the two routes was quantitatively and qualitatively similar. The LCt50 was 5749 mg min m-3 and the subcutaneous LD50 1-2 mg kg-1. Histological changes in the decedents which were similar by both routes of administration were most marked in the lymphoreticular system but also occurred in the gut. Lymphocytolysis and phagocytosis occurred in both the cortex of the thymus and of the lymph nodes. Lymph nodes were more severely affected in the decedents among the animals dosed with T2 by the subcutaneous route. The small intestine exhibited dead and dying cells throughout the lamina propria after T2 by either route.

Aerosols↗