Search PubMed⌕ Search

Biomedical subjects

V J Feron

Publications and source records attributed to V J Feron.

At least 91 records · Page 5Linked to original sources
PubMed1988

Cytotoxic and adaptive effects in rat nasal epithelium after 3-day and 13-week exposure to low concentrations of formaldehyde vapour.

To study in detail possible effects of low concentrations of formaldehyde on the nasal epithelium, Wistar rats were exposed to 0, 0.3, 1 and 3 ppm formaldehyde vapour for 6 h/day, 5 days/week during 3 days or 13 weeks, using in vivo [3H]thymidine labeling for cell proliferation studies, and light and electron microscopy for detecting morphological effects. Compound related histopathological nasal changes varying from epithelial disarrangement to epithelial hyperplasia and squamous metaplasia were found in the 3 ppm group, and were restricted to a small area of the anterior part of the nose which is normally covered with respiratory epithelium. These changes were confirmed by electron microscopy and were not observed in the other groups. Increased cell turnover in the same anterior location confirmed high mitotic activity in the 3 ppm group after 3 days and 13 weeks of exposure. At a slightly more posterior level in the nose a transient response in cell turnover was observed. After 3 days of exposure a nearly log-linear relationship was found between cell turnover and exposure concentration reaching a 10-fold increase in the 3 ppm group, and suggesting challenge of the mucociliary and/or regenerative defence systems not only at 3 ppm but also at 0.3 and 1 ppm. After 13 weeks of exposure mean turnover rates in all exposed groups were markedly lower than after 3 days, and the mean rates of the formaldehyde-exposed groups tended to be below that of the controls. The variation in turnover rate after 13 weeks had increased in a concentration related way, suggesting individual variation in adaptation. The most likely adaptive mechanism at this more posterior level of the nose seemed to be the mucociliary defence apparatus.

Adaptation, Physiological↗
PubMed1988

Nasal tumours in rats after short-term exposure to a cytotoxic concentration of formaldehyde.

Male Wistar rats were exposed to 0, 10 or 20 ppm formaldehyde vapour for 4, 8 or 13 weeks (6 h/day; 5 days/week), and were then observed for periods up to 126 weeks. Transient growth retardation occurred in both test groups. Death rate was not noticeably affected by formaldehyde. Despite recovery periods of at most 126 weeks, the nasal respiratory and olfactory epithelium of many rats of the 20 ppm group exhibited non-neoplastic histopathological changes. Similar but much less severe changes of the respiratory epithelium were seen in a small number of rats of the 10 ppm group; the olfactory epithelium was not visibly affected in rats of this group. Nasal tumours considered to be induced by formaldehyde were seen only in the 20 ppm group and mainly in rats that had been exposed for 13 weeks, the incidence being 4.5% (6/132). These tumours comprised 3 squamous cell carcinomas, 1 carcinoma in situ and 2 polypoid adenomas, all originating from respiratory epithelium. It was concluded that rat nasal respiratory epithelium severely damaged by formaldehyde vapour often does not regenerate and in some cases develops tumours.

Animals↗
PubMed1987

Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure.

As part of a long-term inhalation toxicity study with acetaldehyde in rats, progression and regression of nasal lesions were studied in animals exposed to 0, 750, 1500 and 3000/1500 ppm of the test compound for 52 weeks and killed after recovery periods of 26 or 52 weeks. Major compound-related nasal lesions found at the end of the exposure period comprised: (a) thinning of the olfactory epithelium with loss of sensory and sustentacular cells at all concentrations; this condition was accompanied by focal basal cell hyperplasia in low- and mid-concentration animals; (b) hyper- and metaplasia of the respiratory epithelium frequently accompanied by keratinisation and occasionally by proliferations of atypical basal cells in the top-concentration group; and (c) rhinitis in several top-concentration rats. There was strong evidence on the one hand that the hyper- and metaplastic changes found in the respiratory epithelium and the basal cell hyperplasia seen in the olfactory epithelium after 52 weeks of exposure may progress to neoplasms despite discontinuation of the treatment. On the other hand these hyper- and metaplastic changes may regress during the recovery period. Regeneration of the olfactory epithelium was evident in several low- and mid-concentration animals, but not in top-concentration rats. The regenerated epithelium was seen as a layer of stratified undifferentiated epithelium containing small nerve bundles, tiny groups of sensory cells, and groups of epithelial cells resembling acinar cells of the glands of Bowman. Furthermore, replacement of olfactory epithelium by respiratory epithelium was a frequent finding. It was concluded that rat olfactory epithelium severely damaged by acetaldehyde may regenerate, most probably from basal cells, provided the olfactory epithelium has not been fully destroyed.

Acetaldehyde↗
PubMed1987

Subacute (4-week) inhalation toxicity study of formaldehyde in male rats: 8-hour intermittent versus 8-hour continuous exposures.

Male Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non-exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epithelium.

Animals↗
PubMed1987

Subchronic (13-week) inhalation toxicity study of formaldehyde in rats.

Male and female albino Wistar rats were exposed to concentrations of 0, 1, 10 or 20 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 weeks. Treatment-related changes observed at 20 ppm included in both sexes: stared coats, uncoordinated locomotion and excitation during the first 30 minutes of each exposure, yellowing of the fur, growth retardation, a decreased level of plasma protein, severe and extensive karatinized stratified squamous metaplasia of the nasal respiratory epithelium, and focal degeneration and squamous metaplasia occasionally accompanied by keratinization of the olfactory epithelium; in males only; increased activities of plasma aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and alkaline phosphatase (ALP) and squamous metaplasia of the laryngeal epithelium. Lesions seen at 10 ppm included yellowing of the fur and moderate squamous metaplasia of the nasal respiratory epithelium. The only change observed in three out of twenty 1 ppm exposed animals that might or might not be treatment-related was minimal focal epithelial hyperplasia and squamous metaplasia of the respiratory epithelium lining the nasal septum and maxillary turbinates. No histopathological evidence of hepatotoxicity was detected in any of the formaldehyde-treated groups. An in vivo/in vitro cell proliferation study showed an increase in [3H]-thymidine labeling index of the respiratory epithelium lining the nasoturbinates of rats exposed to 10 or 20 ppm formaldehyde on three successive days, whereas at the 1 ppm level the labeling index was similar to that of controls. It was concluded that under the conditions of the present 13-week inhalation study, formaldehyde at concentrations up to 10 ppm was not hepatotoxic to rats. At the 20 ppm formaldehyde level, a slight effect on the liver of male rats cannot be completely excluded. The study was inconclusive with respect to 1 ppm formaldehyde being a cytotoxic or a no-cytotoxic effect level for the nasal epithelium.

Animals↗
PubMed1987

Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats.

To examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCl4) two 4-week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6-hour exposures by 1.5 hours (2 X 3-hour exposures with a non-exposure interval of 1.5 hour), and peak loads of 5-7 times the basic concentration with or without 1.5-hour interruption of the daily 6-hour exposures. Adverse effects of CCl4 included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCl4 with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6-hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of CCl4 on the liver.

Alanine Transaminase↗
PubMed1986

Significance of the dog as 'second animal species' in toxicity testing for establishing the lowest 'no-toxic-effect level'.

The toxicity data of 66 compounds adequately tested in the rat (as 'prime animal species') and in the dog (as 'second animal species') were studied to find out for how many of these compounds the study in dogs led to a lower 'no-toxic-effect level' (NTEL) than that found in the rat. From a quantitative point of view such information would contribute to a better insight into the desirability of toxicity studies in dogs, because acceptable daily intakes and permissible exposure levels in man are generally based on the lowest NTEL. For 44% of the compounds the NTEL in the dog was lower than that in the rat. When rat NTEL was divided by the arbitrary factor of 10, the adjusted NTEL was lower than the dog NTEL for 86% of the compounds tested in sub-chronic studies, and for 80% of the compounds tested in chronic studies. Whether it is justifiable to substitute such an adjusted NTEL for a study in dogs should be judged from compound to compound. It mainly depends on the size of the margin between the NTEL in the rat (as 'prime animal species') and the (expected) actual exposure level in humans, and also on the acceptability of loosing additional qualitative toxicological information. When this margin is large enough (e.g. 1000 or more), a study in dogs might be superfluous, despite the loss of qualitative data. Such an approach could lead to a reduction of the number of animals in toxicity testing and also to a reduction of the costs.

Animals↗
PubMed1986

The long-term study in rodents for identifying carcinogens: some controversies and suggestions for improvements.

Despite increasing standardisation and international harmonization of the long-term carcinogenicity study in rodents there are still areas of controversy such as high-dose selection, duration of the test period, combining or not combining the chronic toxicity and the carcinogenicity study, the use of historical control data, conditions for redundancy of the study, and significance of studies of restricted design. It is discussed that the 'Maximum Tolerated Dose', or doses above and below the 'metabolic break-point' should be included. In general a test period of 24 months is adequate, but the protocol should be flexible enough to allow extension beyond 24 months. Major advantages of the combined chronic toxicity/carcinogenicity study are that the toxicity and carcinogenicity data are obtained with the same sample of the test compound using the same batch of animals kept on the same diet under the same environmental conditions. It is discussed that the use of historical control data will not lead to a final conclusion on carcinogenic or non-carcinogenic potential of a compound. A long-term carcinogenicity study is considered redundant when adequate (semi-chronic) toxicity studies including reproduction and mutagenicity tests and pre-screens for carcinogenicity, do not indicate mutagenic or carcinogenic activity, and when there is a wide margin (e.g. 1000) between the 'no-observed-adverse effect level' and the (presumed) exposure level in humans. Studies of restricted design and conduct may clearly demonstrate carcinogenicity but also may easily lead to inconclusive results.

Animals↗
PubMed1986

Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats.

The effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4-week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3-h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold. Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound-related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde or interruptedly exposed to 110 ppm with peak loads of 660 ppm. As a consequence 150 ppm acetaldehyde can be considered a 'no-toxic-effect level' in male rats exposed for 6 h/day, 5 days/week, during a 4-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1986

Chronic (89-week) feeding study with hydroxypropyl distarch phosphate, starch acetate, lactose and sodium alginate in mice.

A chronic feeding study was carried out in mice with two chemically modified potato starches, hydroxypropyl distarch phosphate (HP-starch) and starch acetate (AC-starch), and with lactose and sodium alginate. Each of the materials was fed to a group of 75 male and 75 female mice for 89 wk. The dietary level of the test products was gradually increased until the diets contained (by weight) 55% HP-starch, 55% AC-starch, 55% lactose or 25% alginate. The control diet contained 55% pregelatinized potato starch. Each of the four test materials caused increased water consumption, distinct caecal and colonic enlargement, a slightly increased incidence of intratubular nephrosis and, with the exception of AC-starch, also slightly lower body weights. An increased incidence of gastric trichobezoars was observed in mice fed either the modified starches or lactose. The occurrence of concrements in the renal pelvis along with slight urinary changes, such as increased amounts of amorphous material in the urine and increased urinary Ca content, in mice fed HP-starch, AC-starch or lactose was regarded as an effect of little, if any, toxicological significance. Alginate fed at 25% (w/w) of the diet was nephrotoxic to mice, as shown by extremely high water consumption, high urine production, urinary incontinence, high pH and low specific gravity of the urine, increased level of blood urea nitrogen, increased kidney weights, distension of the renal calyx and the high incidence of dilated distal tubules. Caecal and colonic enlargement and changes in urinalysis were found to be reversible and had completely or largely disappeared within 2-5 wk of the cessation of the treatment in wk 87. The incidence of intratubular calcinosis or of concrements in the pelvic space was not reduced during the recovery period. The study did not provide any evidence of carcinogenicity of the products tested.

Alginates↗
PubMed1986

Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study.

Male and female Wistar rats were exposed to acetaldehyde vapour at nominal concentrations of 0, 750, 1500 or 3000/1000 ppm during 6 h/day, 5 days/week for up to 28 months. Major compound-related effects included increased mortality, growth retardation, nasal tumours, and non-neoplastic nasal changes in each of the test groups. The treatment-related nasal changes comprised: (1) degeneration, hyperplasia, metaplasia and adenocarcinomas of the olfactory epithelium at all exposure levels; (2) squamous metaplasia accompanied by slight to severe keratinisation and squamous cell carcinomas of the respiratory epithelium at the 2 highest exposure levels; and (3) slight to severe rhinitis and sinusitis in top-concentration rats. In the larynx hyperplasia and keratinized squamous metaplasia of the epithelium in the vocal cord region were seen in many rats of the mid- and top-concentration groups. One female rat of the 1500 ppm group had developed a laryngeal carcinoma in situ. It was concluded that under the conditions of the present study acetaldehyde is both cytotoxic and carcinogenic to the nasal mucosa of rats. The effects of acetaldehyde on the nose were compared to those of formaldehyde.

Acetaldehyde↗
PubMed1986

Pulmonary response of hamsters to fibrous glass. Clearance and morphology after a single intratracheal instillation.

In a one-year serial sacrifice study 10 mg glass fibres (length, 95% alpha 20 microns, 89% alpha 12 microns, 58% alpha 5 microns and 25% alpha 2 microns; diameter, 88% alpha 1.0 micron, 60% alpha 0.5 micron and 31% alpha 0.25 micron) suspended in 0.2 ml saline solution were administered to Syrian golden hamsters by a single intratracheal instillation to determine the clearance of the glass fibres from the lungs and to examine their effects on the lungs using light and electron microscopy. The clearance was rather efficient with a half-time of about 3 months. Coating and corrosion of glass fibres were sporadic findings. A violent focal acute pneumonitis was evoked by the glass fibres and was followed by excessive accumulations of alveolar macrophages often loaded with glass fibres. Thereafter, "silicotic granulomas" developed which were seen as clusters of tightly packed iron-positive macrophages containing glass fibres. These granulomas were surrounded by a layer of alveolar epithelium, and were by the end of the study the predominant lesion in otherwise normal lungs.

Animals↗
PubMed1986

Spontaneous hyperplastic and metaplastic duct epithelium in the sublingual salivary glands of Wistar rats.

Focal epithelial hyperplasia and metaplasia were observed in the intralobular ducts of the sublingual salivary glands of 302 out of 1142 Wistar rats. These rats (aged 16-145 weeks) served as controls in toxicological experiments. The ductal changes varied from small groups of irregular cylindrical cells with basophilic cytoplasm and vesicular nuclei, with often prominent nucleoli, to large areas of non-keratinized stratified squamous epithelium with marked mitotic activity and necrotic superficial cells being released in the lumen. Mononuclear inflammatory cells were often present in fibrous tissue surrounding altered ducts. Within certain limits the degree and incidence of the changes increased with increasing age; their aetiology is unknown.

Aging↗