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Biomedical subjects

J Schlatter

Publications and source records attributed to J Schlatter.

51 records · Page 3Linked to original sources
PubMed1990

The carcinogenic potential of ethyl carbamate (urethane): risk assessment at human dietary exposure levels.

Ethyl carbamate is found in fermented foods: bread contains 3-15 ng/g, stone-fruit brandies 200-20,000 ng/g, and about one-third of table-wine samples analysed contained more than 10 ng/g. In animals, ethyl carbamate is degraded to CO2, H2O and NH3, with intermediate formation of ethanol. This degradation has been shown to be inhibited (postponed) in the mouse by ethanol concentrations in the blood of about 0.15% and higher. A quantitatively minor pathway involves a two-step oxidation of the ethyl group to vinyl carbamate and epoxyethyl carbamate, the postulated electrophilic moiety that reacts with DNA. This reaction is probably the mode of the mutagenic action observed in many cellular and animal systems. The fact that only vinyl carbamate, but not ethyl carbamate, is mutagenic in a standard Ames test is probably because there is insufficient production of the intermediate oxidation product in the standard test. Consistent with this metabolism is the carcinogenic activity of ethyl carbamate in various animal species and in different organs; this activity can be seen even after a single high dose in early life. Quantitative analysis of the total tumour incidences after chronic exposure of rats and mice to 0.1-12.5 mg ethyl carbamate/kg body weight/day in the drinking-water showed a dose-related increase. The main target organs were the mammary gland (female rats and mice having similar susceptibilities) and the lung (mice only). On the basis of sex- and organ-specific tumour data and with a linear extrapolation to a negligible increase of the lifetime tumour incidence by 0.0001% (one additional tumour in one million individuals exposed for life), a "virtually safe dose" of 20 to 80 ng/kg body weight/day was estimated. The daily burden reached under normal dietary habits without alcoholic beverages is in the range of about 20 ng/kg body weight/day. Regular table-wine consumption would increase the risk by a factor of up to five. Regular drinking of 20 to 40 ml stone-fruit brandy per day could raise the calculated lifetime tumour risk to near 0.01%.

Animals↗
PubMed1986

[Pollution of room air].

In the last decade the significance of indoor air pollution to human health has increased because of improved thermal insulation of buildings to save energy: air turnover is reduced and air quality is impaired. The most frequent air pollutants are tobacco smoke, radioactive radon gas emanating from the soil, formaldehyde from furniture and insulation material, nitrogen oxides from gas stoves, as well as solvents from cleaning agents. The most important pollutants leading to health hazards are tobacco smoke and air pollutants which are emitted continuously from building materials and furniture. Such pollutants have to be eliminated by reducing the emission rate. A fresh air supply is necessary to reduce the pollutants resulting from the inhabitants and their activities, the amount depending on the number of inhabitants and the usage of the room. The carbon dioxide level should not exceed 1500 ppm.

Air Pollution↗
PubMed1982

Heart rate- and ECG-recording in the rat by biotelemetry.

A method for 24 h recording of the heart rate (HR) in unrestrained, freely moving rats is described. Commercially available biotelemetry transmitters were used in combination with normal ranged FM-receivers. The data presented show a pronounced diurnal rhythm in the HR of the rat. When the rats are exposed to noise a large increase in the HR could be demonstrated. The system described is also suitable for analysis of the time parameters of the electro-cardiogram (ECG).

Animals↗
PubMed1979

Differential effects of nicotine and amphetamine on locomotor activity and maze exploration in two rat lines.

Separate groups of two different rat breeding lines, Roman High Avoidance (RHA/Verh.) and Roman Low Avoidance (RLA/Verh.), treated with either saline, nicotine (0.2 mg/kg), or amphetamine (0.4 mg/kg) were compared for exploratory efficiency and for exploratory locomotion by using two different mazes on alternate testing days. The RHA/Verh. rats generally showed more locomotion but less intermaze transfer of exploratory efficency than the RLA/Verh. rats. Nicotine did not alter exploratory efficiency but stimulated locomotor activity in the RHA/Verh. rats, while it did not significantly alter either category of behavior in the RLA/Verh. rats. Amphetamine stimulated locomotor activity in both rat lines but this stimulation was weaker in comparison with that of nicotine. In contrast to nicotine, amphetamine impaired exploratory efficiency in the RHA/Verh. rats. Like nicotine, amphetamine did not significantly affect exploratory efficiency in the RLA/Verh. rats. The results demonstrate that, when the two lines of rats are compared, there is a dissociation of the two categories of behavior and a further differentiation between nicotine and amphetamine effects.

Animals↗
PubMed1976

Effects of nicotine on the exploratory locomotion patterns of female Roman high- and low-avoidance rats.

Utilizing an automated, Dashiell-type hexagonal maze, it was demonstrated that RHA rats: 1) were more active, 2) reversed direction more often, 3) entered radial (blind) alleys less often, and 4) displayed shorter latencies than did RLA rats. Direction reversals (U-turns) tended to increase from day to day with the RHA rats, whereas the opposite was true for the RLA rats. Nicotine injections (0.2 mg/kg) increased activity and the number of U-turns, shortened the latencies and lessened the likelihood of entering radial alleys for both strains. The RHA rats were more sensitive to nicotine than were the RLA rats in all of these measurements, which varied, depending upon alley length and structural complexity, among the maze configurations.

Amines↗
PubMedDate not supplied

Rapid determination of O- and P-cresol isomers in urine from workers exposed to toluene by high-performance liquid chromatography using a graphitized carbon column.

A simple and rapid procedure is described that permits the simultaneous determination of o- and p-cresol in urine of workers of other individuals exposed to toluene. The urine samples are enzymatically hydrolysed and analysed by high-performance liquid-chromatography with a detection limit of 0.2 mg/L, one fifth of the biological threshold limit value for o-cresol (1 mg/g), a specific marker of toluene exposure. A graphitized carbon column Hybercarb-S, that exhibits an excellent selectivity for aromatic positional isomers, was used with 1% phosphoric acid-acetonitrile (70:30, v/v) as mobile phase and a detection wavelength of 271 nm. The overall accuracy for o-cresol determination was 4.5% at 5 mg/L and 8% at 0.5 mg/L. The cresol isomers were sufficiently resolved from endogenous materials to avoid the need for any extraction step, and the method appears suitable for monitoring workers accurately under the permissible level of exposure for occupational medicine purpose.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Ethyl carbamate: analytical methodology, occurrence, formation, biological activity and risk assessment.

Ethyl carbamate (EC) is a genotoxic compound in vitro and in vivo, it binds covalently to DNA and is an animal carcinogen. Today, EC is mainly found as a natural trace constituent in different alcoholic beverages and in fermented food items. Data on analytical methodology and the levels of EC in different food items are summarized and the daily burden of humans is estimated. Under normal dietary habits excluding alcoholic beverages, the unavoidable daily intake is 10-20 ng/kg b.w. On the basis of the evaluation of all toxicity data and its mode of action a conventional risk assessment of EC indicates that this level represents a negligible lifetime cancer risk (less than 0.0001%). Individual habits may greatly enhance the risk. Regular drinking of table wine (500 ml/day) would increase the risk up to 5 times, regular drinking of stone-fruit distillates (20-40 ml/day) would raise the calculated hypothetical tumor risk to near 0.01%. Human exposure to carcinogenic compounds should be as low as reasonably achievable. In order to take reliable measures to reduce EC levels in beverages and foods, it is crucial to know the mode of its formation. For its natural formation the presence of ethanol is absolutely required. In stone-fruit distillates hydrogen cyanide together with photochemically active substances are crucial to form EC. The main part of EC is formed after the distillation involving photochemical reactions. In wine (and probably bread) significant EC formation seems to depend on heat treatment. While in distillates hydrogen cyanide is the most important single precursor, in wine different carbamyl compounds, mainly urea, seem to be involved in EC formation. Despite this apparent difference a common EC formation pathway is discussed for all alcoholic beverages by assuming cyanic-/isocyanic acid as an important ultimate reactant with ethanol. Some ideas are presented as to the possible course of future work.

Carcinogens↗
PubMedDate not supplied

Hazard characterisation of chemicals in food and diet. dose response, mechanisms and extrapolation issues.

Hazard characterisation of low molecular weight chemicals in food and diet generally use a no-observed-adverse-effect level (NOAEL) or a benchmark dose as the starting point. For hazards that are considered not to have thresholds for their mode of action, low-dose extrapolation and other modelling approaches may be applied. The default position is that rodents are good models for humans. However, some chemicals cause species-specific toxicity syndromes. Information on quantitative species differences is used to modify the default uncertainty factors applied to extrapolate from experimental animals to humans. A central theme for extrapolation is unravelling the mode of action for the critical effects observed. Food can be considered as an extremely complex and variable chemical mixture. Interactions among low molecular weight chemicals are expected to be rare given that the exposure levels generally are far below their NOAELs. Hazard characterisation of micronutrients must consider that adverse effects may arise from intakes that are too low (deficiency) as well as too high (toxicity). Interactions between different nutrients may complicate such hazard characterisations. The principle of substantial equivalence can be applied to guide the hazard identification and hazard characterisation of macronutrients and whole foods. Macronutrients and whole foods must be evaluated on a case-by-case basis and cannot follow a routine assessment protocol.

Animals↗
PubMedDate not supplied

[Fast diagnostic tests in the management of group A beta-heamolytic streptococcal pharyngitis].

OBJECTIVE: Routine clinical diagnosis of Streptococcus pyogenes in pharyngitis is not always easy. The use in common practice of rapid diagnosis test (RDT), might offer a best control of the antibiotic treatments. The aim of this study is to present seven rapid diagnosis tests, to assess their feasibility and finally to determine the bacteriological correlation. METHOD: We propose to compare the results obtained with seven RDT, and to assess their interest in medical diagnosis for group A streptococcus pharyngitis. A prospective study was conducted for three months, a RDT was performed for children (n=75) between eight and fourteen years old presenting acute pharyngitis. Several throat sampling were performed to order cultures. RESULTS: The group A streptococcus was isolated in 33% (n=25) of throat sampling. Comparing cultures results, and for all studied tests, we obtained comparable performances with manufacturer data, specificity upper than 94% and sensitivity upper than 88%. CONCLUSION: All assessed RDT may offer to physicians a decision-making tool for rapid diagnosis. However, because of its complexity, the agglutination test can be used only in pathology laboratories.

Adolescent↗
PubMedDate not supplied

Correlation of telemetered heart rate and locomotor behavior in cyclazocine treated rats.

Two experiments were performed to verify the validity of a biotelemetry system for 24 hour recording of heart rate (HR) of rats in behavioral toxicology. As test substance the hallucinogenic drug cyclazocine was used at various dose levels (0.1, 0.75, 1.5 and 3.0 mg/kg SC). In a first experiment, female rats were tested in their home cage. It was found that HR was altered by cyclazocine during the four hours following drug injection. This alteration was biphasic: immediately after injection, when control HR was high, cyclazocine lowered HR. In contrast, one hour after the injection, when control HR was low, cyclazocine increased HR. The duration of this increase of HR was dose-dependent, while the magnitude was not. In a second experiment male rats were tested in a residential maze: simultaneously to the rat's HR, locomotor activity was recorded. The results of the first experiment were confirmed and extended to males as well as to a different environmental situation. The additional behavioral data showed a different aspect of cyclazocine action: 0.75 mg/kg initially decreased and later increased activity while 3.0 mg/kg first did not alter activity and later increased it, leading to a dissociation between HR and activity. The findings demonstrate that recording of HR adds a new dimension to the data obtained in conventional behavioral tests. The results are discussed with regard to behavioral and neurochemical effects of the drug.

Animals↗