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Biomedical subjects

R Kroes

Publications and source records attributed to R Kroes.

At least 55 records · Page 3Linked to original sources
PubMed1983

Tissue damage and nutritional factors in experimental respiratory tract (Co-)carcinogenesis.

Cofactors involved in respiratory tract carcinogenesis were studied in Syrian golden hamsters or in rats using benzo(a)pyrene as the carcinogenic agent. These factors included severe tissue damage induced by electro-coagulation, glass fibers administered by intratracheal instillation, acetaldehyde as irritant vapor, food restriction, and nutrients such as vitamin A and saturated and unsaturated fats. In addition, the effects of a combined exposure to four different major gaseous cigarette smoke components--methyl nitrate, isoprene, methyl chloride and acetaldehyde--and to one solid cigarette smoke component--norharman--were examined in short- and long-term inhalation studies. An interesting finding was the carcinogenicity of acetaldehyde, of which the possible mechanism is briefly discussed. Another conspicuous observation was the substantial increase in number and size of lipid droplets in alveolar fibroblasts of hamsters fed a high vitamin A diet.

Acetaldehyde↗
PubMed1981

[Foods of animal origin and public health (author's transl)].

Modern society adopts a highly ambiguous attitude towards foods of animal origin in human nutrition. Animal protein is of great biological value. However, the wealthy part of the world already consumes more than sufficient protein, which renders this value superfluous. On the other hand, a rich diet including a large share of animal products is suspect from the point of view of cardiovascular disease, cancer, osteoporosis and nephrolithiasis. The role of fat, protein, cholesterol, salt, calcium and a number of minor components is discussed. It is concluded that as far as fats are concerned, reduction is indicated. There is a large individual variability in response to salt and cholesterol as well as interactions with other components of the diet. A role of animal protein in affecting calcium metabolism is plausible, though not definitely established. Public health hazards due to contaminants are probably small compared with those caused by the major components.

Cardiovascular Diseases↗
PubMed1981

Histopathological profile of a Wistar rat stock including a survey of the literature.

This study is concerned with the histopathological changes and tumors and their incidences in the Wistar SPF Tox rat. Also included are data on survival, growth and haematology. The animals were untreated and were investigated for 30 months. The data are compared with those from two Wistar substocks, which had been used in the same laboratory: the Wistar CPB and the Wistar Conv. The results are summarized in tables and figures and are compared with data from the literature. A survey of studies dealing with spontaneous lesions and tumors in rats is given. A wide variety of tumor types and a relatively high tumor incidence were found in the Wistar SPF Tox rats. Since most of the tumors were found after 24 months, this high incidence was correlated with the life expectancy.

Animals↗
PubMed1977

Short-term toxicity of strontium chloride in rats.

A range-finding experiment with strontium chloride hexahydrate (0, 3, 30, 300 and 3000 ppm in the diet) and subsequently a 90-day test with the same compound at dose levels of 0, 75, 300, 1200 and 4800 ppm in a semipurified diet was carried out with SPF-derived Wistar-rats. The diet contained adequate levels of Ca, Mg, P and Vit.D3. Growth, food intake, behaviour and mortality were measured, extensive haematology and clinical biochemistry carried out, organ weights determined, X-ray photographs of the bones taken and complete histopathological examination was performed. In addition Sr-content of blood, bone and muscles was determined. Thyroid weights were significantly increased in the males of the 1200 and 4800 ppm group. Histological evidence for increased thyroid activity was noticed in the males of the 4800 ppm group. Pituitary weights were significantly decreased in the females of the 300 ppm and 4800 ppm group, but not of the 1200 ppm group. A histologically confirmed glycogen depletion of the liver was noted biochemically in the highest dose group (4800 ppm). Sr-content in bone was increased at all dose levels having a constant level from 4 weeks onwards, thus indicating that a no effect level cannot be established. If the increased Sr-concentration in the bone can be considered a non-toxic effect, the non-toxic effect level appears to be 309 ppm.

Animals↗
PubMed1976

Toxicity of methylmercury chloride in rats I. Short-term study.

In the range-finding test, 6 groups of 4 male and 4 female weanling rats were given dietary levels of 0, 0.1,0.5, 2.5, 12.5 and 250 ppm methylmercury chloride (MeHgCl) for 2 weeks. Signs of central nervous system toxicity, weight loss and high mortality appeared at 250 ppm but not at lower levels. No haematological changes were observed at 0.1-12.5 ppm. The relative weights of the liver in females on 2.5 and 12.5 ppm and of the kidneys in females on 12.5 ppm were significantly increased; the effects in males were less marked. Total mercury concentration in the kidneys increased proportionally with increasing dietary levels of MeHgCl. In the short-term test, 5 groups of 15 male and 10 female weanling rats were given dietary levels of 0, 0.1, 0.5, 2.5 and 25 ppm MeHgCl for 12 weeks. Toxic signs, weight loss and restricted food intake were observed at 25 ppm starting from week 9 onwards. Haematological, serum enzyme and urinalysis changes were seen at 25 ppm. Liver microsomal enzyme activity was increased non-significantly and liver glycogen was depressed at 25 ppm. Organ weight changes were evident at 25 ppm and histological changes seen in the spleen, kidneys, brain, spinal cord and peripheral nerves were confined to the 25 ppm level. Histochemical changes in kidney enzymes occured at 2.5 and 25 ppm. Hg concentrations in blood, hair, kidneys, liver and brain were higher at 12 weeks than 6 weeks and generally increased with increasing MeHgCl level in the diet.

Animals↗
PubMed1976

Toxicity of methylmercury chloride in rats. II. Reproduction study.

A reproduction study over 3 generations of rats was carried out in which groups of 20 female and 10 male rats received in the diet 0, 0.1, 0.5 and 2.5 ppm MeHgCl. The parameters studied included growth, food intake, haematology, serum and urinalysis, organ weights and reproductive performance, No effect was exerted on fertility index, lactation index or on the 21-day body weights of pups but the viability index was impaired at 2.5 ppm in the F1 and F2 generations. Weight gain reductions observed at 12 weeks for the 2.5 ppm level were not accompanied by reductions in food intake. At 6 months, Fla females on 2.5 ppm showed a reduced leucocyte count whilst P males on 0.5 and 2.5 ppm showed an increase in neutrophils and a decrease in lymphocytes. The relative weights of the kidneys, heart, spleen brain and thyroid were increased at 2.5 ppm and in some cases the increases of kidney weights were inconsistently seen at the 0.1 and 0.5 ppm levels. No significant histological changes were seen at any level. In a special 7-week study involving the F3a generation, weanling rats obtained from the four different F2a groups, each comprising 20 females and 10 males, were all transferred to diets containing 25 ppm MeHgCl. Toxicity signs were evident at 7 weeks. No evidence was obtained of increased susceptibility to the toxicity of MeHgCl in successive generations.

Abnormalities, Drug-Induced↗
PubMed1976

Toxicity of methylmercury chloride in rats. III. Long-term toxicity study.

Four groups, each of 25 male and 25 female weanling rats, were given dietary levels of 0, 0.1, 0.5 and 2.5 ppm MeHgCl for 2 years. Observations were made on behaviour, growth, food intake, haematology, serum enzymes, urinalysis, microsomal liver enzymes, organ weights and histology with special reference to the nervous system, histochemistry of the kidneys and cerebellum and on tissue Hg concentrations. Significant findings included a slight growth reduction in females at 2.5 ppm, increased relative kidney weight at 2.5 ppm and histochemical changes in kidney enzymes at 2.5 ppm. No effect was seen on the nature or incidence of pathological lesions or tumours at any level. From the results obtained in the short-term, reproduction and long-term studies, the no-toxic effect level for rats appears to be between 0.1 and 0.5 ppm MeHgCl in the diet. Exposure of the Dutch population does not appear to present a health hazard at the moment because the mean intake of total Hg is still far below the intake deemed to be safe.

Animals↗
PubMed1976

Short-term toxicity of 1-naphthaleneacetic acid in rats.

In a 90-day feeding study, 4 groups of 10 male and 10 female rats received in the diet 0,200, 1000 and 5000 ppm 1-naphthaleneacetic acid (1-NAA). Growth and food intake was reduced significantly only in males on 5000 ppm. Haematological examination yielded essentially negative results except for a non-significant reduction at the 1000 and 5000 ppn levels in the leucocyte count, mainly due to a reduction in neutrophils. No significant effects were observed in the renal concentration test, urinalysis, renal histochemistry or histology of a wide range of organs at any level of 1-NAA tested. Increased relative weights of thyroid, testes, brain and liver were confined to the 5000 ppm level. The increase in relative liver weight was not accompanied by histological liver damage and was associated with elevated liver microsomal enzyme activity. The loss of glucose 6-phosphatase (G6Pase) and increase in glucose 6-phosphate dehydrogenase (G6PDH) seen histochemically in the centrilobular region of the liver in males on 5000 ppm, accompanied by glycogen depletion in the liver, could however be indicative of liver damage. On the basis of conventional criteria, a no-effect level of 1000 ppm would have been indicated by this study but in view of liver glycogen depletion at all levels tested a no-effect level was not established.

Animals↗
PubMed1976

Methods for controlling the application of anabolics in farm animals.

In the use of anabolic agents, the most pronounced effect on growth is caused by estrogens. For this reason primarily attention will be given to the methods of detection of estrogen administration to fattening animals. The detection methods can mainly be divided in histological, biological, chemical, and immunological determinations and these will be briefly discussed in the light of the present situation in many countries, where the use of anabolic agents is prohibited. From the point of view of control, this prohibition is much easier to handle than a situation in which the application of some specified products is permitted. The possibilities and limitations of control, when certain anabolic agents are permitted for use, will be discussed and evaluated. The conclusion is drawn that in this latter case a sufficient control is very difficult if at all possible considering the methods of control available at the time.

Anabolic Agents↗
PubMed1975

Long-term toxicity and reproduction studies with metaldehyde in rats.

Rats received 0, 200, 1000 and 5000 ppm metaldehyde in the diet for 2 years. Reproduction studies over three generations using the same dietary levels were carried out. In the third litter of each generation attention was paid to possible embryotoxic or teratogenic effects. The parameters studied included growth, food intake, behaviour and survival, haematology, clinical biochemistry, organ weight, histopathology, reproductive performance and teratogenicity. At 5000 ppm the relative liver weight was increased and this was accompanied by an increase in liver microsomal enzyme activity. The most striking observation was a dose-related development of posterior paralysis in females due to a transverse lesion of the spinal cord. The latency period was more than 550 days. Three rats with posterior paralysis showed a transverse lesion of the spinal cord. No significant histological damage to other organs was seen. The tumour incidence was not increased in any of the metaldehyde dosage groups. The reproduction study confirmed the findings of the long-term test. Posterior paralysis appeared in at least 50% of the females on 5000 ppm metaldehyde in all 3 generations. Some were affected at 1000 ppm but none at 200 ppm. Histologically, a fracture or distortion of thoracic vertebrae and subsequent compression of the spinal cord was found. The onset of paralysis was related to the time of delivery. The reproductive performance was susceptibility in this respect to metaldehyde. Apart from one male rat on 200 ppm with clinical posterior paralysis without transverse lesions in the spinal cord, this level was without toxic effects both in the long-term and 3-generation reproduction study.

Acetaldehyde↗
PubMed1975

Short-term oral and dermal toxicity of MCPA and MCPP.

The herbicieds 2-methyl-4-chlorophenoxy acetic acid (MCPA) and 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP or mecoprop) were tested for 90 days in rats. The compounds were added to the diet at levels of 0, 50, 400, and 3200 ppm. Growth, food intake, mortality, haematology, blood and liver chemistry, organ weights and histopathology were used as criteria. The main effects of both compounds were growth retardation and elevated relative kidney weights at levels of 400 ppm and more. The 50 ppm dose level can be considered as a no-toxic-effect level in the 90-day study. In subacute dermal studies in rabbits during 3 weeks the dosages were 0, 0.5, 1.0 and 2 g MCPA or MCPP per kg body weight. Therafter followed a recovery period of 2 weeks. Growth, mortality, skin reaction, haematology, organ weights (MCPP) and histopathology were recorded and determined. Both compounds caused slight to moderate erythema at all dose levels, whereas elasticity of the skin was decreased. In both experiments the skin returned to normal during the recovery period. Weight loss was observed at all dose levels. In the MCPA experiment high mortality and histopathological changes in the liver, kidneys, spleen and thymus were recorded at the two highest dose levels. The cause of this could have been either the treatment with MCPA or a dysbacteria infection which developed during the experiment. Oral and intraperitoneal acute toxicity of MCPP for the rat were found to be 1210 and 402 mg/kg, respectively. After a single oral or dermal application of MCPA to the rabbit, the compound was excreted unchanged in the urine.

Administration, Oral↗