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Biomedical subjects

P Clausing

Publications and source records attributed to P Clausing.

At least 37 records · Page 2Linked to original sources

Total RNA content of brain cells of inbred mice reared under different conditions.

AB/Jena, DBA/2Jena, C57B1/6 Jena inbred mice and ABD2F1- and B6D2F4-hybrid mice either were reared communally and weaned at day 30 or were reared by isolated mothers and weaned at day 21 (I21). On day 50 the total RNA content of pyramidal brain cells of male offspring was determined by cytophotometry. The studied brain areas were the frontal pole of cerebral cortex (FCC) and the CA1 region of the dorsal hippocampus (DHI). The DBA, C57 and ABD2 mice had a reduced FCC and DHI RNA-content under I21-rearing. Under these conditions the AB strain has the highest RNA-content in both substrates. The results call for the awareness of possible genetic influences when studying the effects of environmental enrichment/impoverishing.

Animals↗

[The subacute and subchronic toxicity of chlorophacinone in Japanese quail (Coturnix c. japonica)].

Accordingly to the subacute toxicity of chlorphacinone to Japanese quail (LC 50: 60 mg/kg feed), the uptake of Delicia-chlorphacinone-baits for several days can be lethal to birds as a matter of principle. A subchronic study resulted in a "no-observed-effect-level" of 1 mg chlorphacinon/kg feed. Reproduction is not affected until dose levels which resulted in lethality or are accompanied by physiological changes (coagulability of blood, microcytic anaemia). Increased sensibility of descendants to chlorphacinone cannot be derived from the findings.

Animals↗

Effects of drinking water acidification, restriction of water supply and individual caging on parameters of toxicological studies in rats.

A 21 week experiment was conducted with male SPF Ico/Shoe: WIST rats to study the influence on diagnostic parameters of toxicological studies of (i) acidification of drinking water by hydrochloric acid (untreated tap water vs. pH 3 vs. pH 2), (ii) individual vs. group caging (5 animals/cage), and (iii) ad libitum vs. 10 ml restrictive water supply. Acidification to pH 2 resulted in a slightly but significantly reduced excretion of phenol red, lowered proteinuria and a decreased urine volume, whereas all other parameters remained unchanged. Individual caging was less stressful than expected from published data. Red blood cell counts were increased, water consumption and urine volume were somewhat lowered, but stress-sensitive parameters like adrenal weight, leucocyte and lymphocyte counts were not altered. A 10 ml restrictive water supply decreased urine volume, food consumption, body weight development and organ weights. Furthermore transient increases in red blood cell counts and hemoglobin contents, leucopenia and--most important--an impaired renal function were observed. In conclusion acidification of drinking water with hydrochloric acid should not be lower than pH 3, male Ico/Shoe: WIST rats can be regarded as minimum susceptible to individual caging, and reduced water intake might give false positive nephrotoxic effects.

Animals↗

A method for estimating soil ingestion by children.

In recent years, many cases of soil pollution have been unearthed in the Netherlands. The ingestion of soil particles due to mouthing behaviour of young children is an important potential pathway of exposure and may constitute a health risk. For an assessment of these health risks, a reliable estimation of the daily inadvertent ingestion of soil particles is necessary. A method to estimate soil ingestion is the use of titanium (Ti), aluminium (Al) and acid insoluble residue (AIR) content of the soil as a tracer. By measuring these tracers in faeces of children and in soil, an estimate can be made of the amount of soil ingested. This method can be used if the following conditions are met: tracer intake by other routes (food) is low and not too variable; tracer absorption from soil in the gastro-intestinal (GI) tract is negligible; tracer concentrations in soil are high and not too variable. A small pilot study was conducted among 18 children visiting a nursery school and 6 hospitalized children without any possibility of soil contact. The results of the pilot study indicate that each tracer is present in faeces in highly variable amounts, but that a combination of these three tracers produces a useful picture of potential soil ingestion. Quantitatively, a difference between the two populations of 55 mg/d, expressed as soil ingestion, was found. Despite the small numbers involved, this difference was statistically significant as the population standard deviations were small. In a number of different soil types, tracer concentrations were found to be almost equal. Further studies are planned to test the validity of the assumptions, and to investigate larger child populations living in different circumstances.

Administration, Oral↗

Variability of exposure measurements in environmental epidemiology.

In studies in environmental epidemiology, exposure to harmful agents is often highly variable in time and space. It is not usually possible to measure the relevant, personal exposure of study subjects to these agents directly. Instead, exposure measurements are performed at fixed sites and/or for limited periods of time in many cases. Such measurements are imperfect in the sense that they only approximate the "true" personal exposure of study subjects. When measures of exposure are highly variable in time and space, single measurements approximate the true exposure only to a limited extent. The variability of measures of exposure can be investigated by repetition of the measurements in time and space. Analysis of variance techniques can be used to separate the within-subject or "error" variance from the between-subjects or true variance. Computation of the ratio between the error variance and the true variance is a useful technique to evaluate the potential bias in correlation and regression coefficients calculated with these measures of exposure. Using data from a number of different studies, the authors have estimated the variance ratio of lead exposure and nitrogen dioxide exposure variables. The results suggest that these ratios may be large. Empirical illustrations are given of bias in regression coefficients of childhood blood levels on different lead exposure variables. It is recommended that pilot studies be performed more routinely to estimate the magnitude of the variance ratios of exposure variables of interest in studies in environmental epidemiology.

Adolescent↗

Toxicokinetics of the herbicide dichlorprop and its leucinate and their action on liver mixed function oxidase in rats.

The concentrations of dichlorprop and its leucine conjugate in serum and bile of rats have been determined at different periods after a single oral dosage of these compounds (30 or 300 mg/kg body weight). From the results it can be concluded that dichlorprop is excreted by active renal mechanisms resembling that described for 2,4,5-T. It is suggested that the leucinate is excreted more by the biliary route. Investigations of the liver demonstrate that both compounds are able to induce mixed function oxidases.

2,4-Dichlorophenoxyacetic Acid↗

Differences in the distribution of methyl mercury in erythrocytes, plasma, and brain of Japanese quails and rats after a single oral dose.

Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.

Animals↗

Iron overload of spleen, liver and kidney as a consequence of hemolytic anaemia.

Iron overload in spleen, liver and kidney induced by hemolytic anaemia due to a 90-day oral exposure of rats to diuron (N-3,4-dichlorphenyl-N,N-dimethylurea), an urea herbicide, was studied by histochemistry, transmission electronmicroscopy, morphometry and energy dispersive X-ray microanalysis. Increasing dosages of diuron provoked a hemosiderosis in the spleen followed by erythrocytic sequestration and the formation of haemopoietic foci coinciding with Kupffer cell siderosis of the liver. A strong enlargement of the spleen red pulp on the one hand faces an unchanged total white pulp volume as well as no alterations of the white pulp microscopic structure on the other. The electron dense bodies of the endothelial cells did not contain iron whereas hepatocytes possess two types of lysosomes, homogeneous iron containing ones at the sinusoidal site and complex structured ones without detectable iron at the biliary site. The formation of the homogeneous lysosomes is suggested to be due to the hepatocytic reception of hemoglobin-haptoglobin-complexes after intravascular hemolysis. The lysosomes of the biliary site seem to be engaged in hemoglobin degradation. A partial nephrohydrosis due to hemosiderotic events in succession of intravascular hemolysis including hemoglobin reabsorption from the primary urine could be observed. It is assumed that exocytosis might play a major role in hemosiderin removal from kidney tubule cells.

Anemia, Hemolytic↗

Aspects of methodology employed in the investigation of combined chemical effects on acute oral toxicity.

The evaluation of combined chemical effects should be based on the theoretical additive LD50 values which are derived from the LD25 values of the single substances rather than the 1/2 LD50 values. If the latter are used, misinterpretation of the character of the combined action (overestimation of antagonism/underestimation of potentiation) are not excluded, particularly in case of low slope functions.

Administration, Oral↗

[Acute toxicity of mercurial seed-dressing agents for rats and Japanese quail with special reference to coergistic effects].

Acute oral toxicity to rat of phenyl-mercury acetate (with 44 mg/kg on males and between 54 mg/kg and 77 mg/kg on females several tests) was found to be almost identical with that of methyl-mercury toluenesulphamide (59 mg/kg on males, 54 mg/kg on females). Japanese quail, on the other hand, proved to much more sensitive to the methyl compounds, the significant difference being 25 mg/kg of methyl-mercury toluenesulphamide against 71 kg/kg of phenyl-mercury acetate. Coergistic action of combinations of phenyl-mercury acetate with HCB, Lindan, and Carboxin on female rats generally was poor. No deviation was established from additive action by a recently proposed method of evaluation. Conventional evaluation by means of an association factor (V) gave an antagonistic effect for the combination with Lindan (V = 0.54) and a potentiative effect for the combination with Carboxin (V = 1.70).

Animals↗

[Subchronic toxicity of gamma-Falisan-Universal dry dressing agent to rats].

Doses of 50 mg/kg, 100 mg/kg, and 400 mg/kg of Gamma-Falisan-Universal dry dressing agent (active ingredients including 20 per cent of Lindan and 2.5 per cent of phenyl-mercury acetate) were administered in agar suspension by stomach intubation to rats over 13 weeks, with five applications weekly. The following changes were produced: retardation in body weight, lymphopenia and leucopenia, rise of segment-nuclear neutrophils in peripheral blood, decrease of haematocrit and haemoglobin, as well as rise in activities of leucine aminopeptidase and serum glutamate oxalo-acetate transaminase. The males proved to be more sensitive in the context of their haematological parameters, while the females displayed higher sensitivity in terms of clinico-chemical values. Absolute weight increases were recorded from kidneys and liver of both males and females and from the adrenal gland of females, while weight loss was recorded from the pituitary gland of males. Changes of the same kind were expressed even more strongly, in the context of relative weights of organs. Histopathological changes were recorded from liver, kidneys, and adrenal gland of either sex, and they were histometrically confirmed. Retardation in body weight, rise in activity of leucine aminopeptidase, and weight changes of various organs were significant up to first dosage group. Analogous findings were obtained with regard to microscopic changes in kidneys. Hence, no-effect levels did not occur at all throughout the experiment.

Adrenal Cortex↗

[Critical remarks on the investigation methods of coergistic effects of acute oral toxicity of combination insecticides].

Often the application of fractions of the LD50 (e.g. 1/4 LD50, 1/2 LD50) is unavoidable due to technical conditions in the experiment (e.g. in case of substances with low toxicity and in case of very steep slope functions). But if ever possible, dosage of equitoxic amounts (LD10, LD50 etc.) should be prefered, because of higher reliability in the choice of dosage and evaluation of the results. Benefits and disadvantages of the two experimental principles are demonstrated by results of own investigations.

Animals↗