Exposure to polycyclic aromatic hydrocarbons among Dutch children.

We determined the urinary 1-hydroxypyrene (1-HP) concentration and the creatinine-adjusted 1-HP concentration in 644 randomly selected Dutch children, aged 1-6 years and living in five areas with roughly different levels of polycyclic aromatic hydrocarbons (PAHs) in soil and ambient air. The presence of other factors that might influence the exposure to PAHs was studied using a questionnaire. To evaluate the reliability of a single urinary 1-HP determination, measurements were repeated after 3 weeks for approximately 200 children. The mean urinary 1-HP content of the total study population was 2.06 nmol/l. This varied from 1.58 nmol/l in the reference area (Flevoland) to 2.71 nmol/l in the valley of the Geul. Only indoor sources of PAHs showed a small, positive association with urinary 1-HP. The urinary 1-HP concentrations of children from the valley of the Geul were higher (p < 0.01) and those of children from a suburb of Amsterdam were lower (p < 0.01) than those of children from the reference area. The possible ambient environment-related differences were probably too small to be detected in the variations of the intake of PAHs from the daily diet. The reliability of a single 1-HP measurement was low. Similar results were obtained with the creatinine-adjusted data. In one neighborhood built on coal-mine tailings, the urinary 1-HP content in children was weakly but positively associated with the PAH content in the upper soil layer of the garden of their homes. However, this association was not found for the children from the other neighborhood built on coal-mine tailings and with similar PAH levels in soil.

Discriminative stimulus properties of midazolam: comparison with other benzodiazepines.

Rats (N = 12) were trained to discriminate midazolam (1 mg/kg, IP) from vehicle in a food reinforced operant conditioning procedure. Midazolam, flunitrazepam, diazepam, chlordiazepoxide and pentobarbital showed dose-dependent substitution for midazolam. Buspirone and Ro 15-1788 did not substitute for midazolam. The midazolam cue was dose-dependently antagonized by Ro 15-1788. In rats (N = 12) trained to discriminate chlordiazepoxide (3 mg/kg, IP) from vehicle midazolam, flunitrazepam, diazepam and chlordiazepoxide substituted completely and dose dependently for chlordiazepoxide. The relative potency of chlordiazepoxide and diazepam was three times less in the midazolam-trained animals than in the chlordiazepoxide-trained animals. Response rate and latency data further support the main finding that the midazolam cue is similar, but not identical to the cue of classical benzodiazepines.

Characterisation of the discriminative stimulus properties of flumazenil.

Rats were trained to discriminate flumazenil (15 mg/kg i.p.) from vehicle in a two-lever, food-reinforced, operant conditioning procedure. Substitution tests were performed with a wide dose range of flumazenil and of several benzodiazepines and non-benzodiazepine compounds possessing behavioural effects similar to or opposite to those of benzodiazepine agonists. The results indicate that low doses of flumazenil have behavioural effects, that the flumazenil cue has a low degree of specificity and is most strongly related to the stimulus properties of benzodiazepines.

Discriminated taste aversion with chlordiazepoxide.

Discriminative stimulus effects have been studied extensively with the two-response, food-reinforced operant procedure and more recently also with discriminated taste aversion (DTA) procedures. DTA procedures have the advantage of a more rapid discrimination training. However, the test phase, i.e., drug substitution, of the DTA procedure is more time consuming (1 test per 4 days) than the test phase of the two-response procedure (2 tests per 5 days). The present study investigated whether a DTA procedure with 2 tests per 5 days could be implemented. In addition, the specificity of the DTA procedure was investigated. Rats were trained to discriminate chlordiazepoxide (CDP, 20 mg/kg, IP) from vehicle using a discriminated taste aversion procedure. Selective suppression of saccharin consumption after CDP injections was maximal after seven CDP-LiCl pairings. In subsequent substitution tests, with 2 tests per 5 days, CDP-mimicking effects were found only for another benzodiazepine, diazepam, and for a barbiturate, pentobarbital. The results indicate that rats can be rapidly trained to discriminate CDP from vehicle in the discriminated taste aversion procedure and that the CDP-cue so produced has the same specificity as in a two-response, food-reinforced operant procedure. However, the DTA procedure has a number of drawbacks that make its advantage over the two-response procedure questionable.

Ethanol suppression of schedule-controlled responding: interactions with Ro 15-4513, Ro 15-1788 and CGS 8216.

Rats (N = 14) were trained to respond under a five seconds differential reinforcement of low rate (DRL 5'') schedule and under a fixed ratio 10 (FR10) schedule of reinforcement. Ro 15-1788 did not influence the number of responses in the DRL 5'' schedule, but increased responding in the FR10 schedule. Ethanol (ETOH, 1250 mg/kg) and CGS 8216 (5 mg/kg) suppressed responding in both schedules and these effects were not antagonized by Ro 15-1788. The response suppressing effects of ETOH in both schedules were not influenced by CGS 8216. These results indicate that the response suppressing effects of ETOH and CGS 8216 are not mediated by the BDZ receptor. Ro 15-4513 suppressed responding strongly in the FR10 schedule. The response suppressing effects of Ro 15-4513 were additive with the response suppressing effects of ETOH. In rats (N = 11) trained to respond under a variable interval 40 seconds-fixed ratio 10 (VI 40''-FR10) schedule Ro 15-4513 dose-dependently suppressed responding. These results indicate that Ro 15-4513 has sedative effects and is not able to antagonize all the behavioral actions of ETOH.

The long-term effects of diazepam and pentylenetetrazol on the potentiated startle response.

Stress desensitization is observed as a decrease in the disruptive effects of a stressor on behavior when the organism is repeatedly exposed to the stressor. For instrumental behavior, stress desensitization was also reported for rats preexposed to anxiogenic drugs; stress sensitization was reported for rats preexposed to an anxiolytic compound. The present study investigated whether similar effects are found in a noninstrumental task situation. First, rats received 12 daily injections of pentylenetetrazol (PTZ, 20 mg/kg, IP), diazepam (DZP, 5 mg/kg, IP) or saline. After each injection the effect of the drugs on the acoustic startle reflex was measured. No drugs were given during the remainder of the experiment. Eight days later rats were given 5 days of Pavlovian fear conditioning to establish a light as a shock signal. During the next 3 days, potentiation of the startle response by the light was measured. None of the drug treatments had an effect on startle potentiation, indicating that stress sensitivity is not affected by previous administration of PTZ and DZP in a noninstrumental task. An explanation for the different effects found for instrumental and noninstrumental tasks is suggested.

Perceptual differences regarding health and environmental problems and their remedies in two states of the former Czechoslovakia.

In the framework of the Central European Study on Air pollution and Respiratory Health (CESAR), a risk perception and risk communication study was carried out in a total of 25 areas in Bulgaria, the Czech Republic, Hungary, Poland, Romania and the Slovak Republic. This paper is focused on the differences of perception between the Czech (CR) and the Slovak Republic (SR), and the other involved countries. The analysis is based on the data of a structured risk perception questionnaire survey of a random population sample. 6,043 completed questionnaires were collected from the total number of 14,400 distributed ones in 25 areas of the 6 countries. The risk perception was different in the CR and the SR, mainly concerning local environment and health of children in the CR and drug abuse including alcohol consumption and AIDS in the SR. In both countries environmental and health problems were seen as important, but the perceived responsibility for finding a solution was placed with different kinds of institutions.

[Blood lead levels in young children in The Netherlands]. / Concentraties lood in het bloed van jonge kinderen in Nederland.

OBJECTIVE: Determination of lead content in blood (Pb-B) of young children in the Netherlands, to assess the influence on Pb-B of the ambient environment and to verify a surmised decrease of Pb-B. DESIGN: Cross-sectional study. SETTING: Centres and suburbs of Rotterdam and Amsterdam villages in the Geul Valley (Limburg), neighbourhoods in urban areas in Limburg and Flevoland. METHOD: Randomly selected children aged 1-6 years, residing for at least 2 months in the aforementioned areas, provided a venous blood sample, in which Pb-B was determined. RESULTS: Pb-B of 559 children investigated, varied from 20 micrograms/l through 224 micrograms/l and showed no clear association with age. Mean Pb-B of girls (48.5 micrograms/l) was slightly lower than that of boys (52.5 micrograms/l). Mean Pb-B was highest in children from the centre of Rotterdam, followed by that in children from the centre of Amsterdam, the suburbs of Rotterdam and Amsterdam, the Geul Valley and Lelystad, while children from Flevoland and the neighbourhoods in urban areas in Limburg had the lowest Pb-B. In children from the city centres Pb-B had decreased since 1979 by 62% (Amsterdam) and since 1981 by 52% (Rotterdam). In children from the suburbs of these cities these decreases amounted to 57% and 39% respectively. CONCLUSION: Pb-B of young children in the Netherlands has decreased to a mean of 64 micrograms/l in children from the city centres and to a mean of 45 micrograms/l in children living outside the city centres. Among the children from the inner cities, 2.7% had a Pb-B higher than 150 micrograms/l and 6.7% a Pb-B higher than 100 micrograms/l.

Cluster management and the role of concerned communities and the media.

Public health services often have to deal with reported clusters of adverse health events. An important characteristic of disease clusters is that the involved community often is concerned about environmental factors influencing health. To facilitate cluster investigations, a stepwise protocol was developed in the Netherlands, based on international literature. Essential is the two-way approach, consisting of a disease-track and an environment-track. Attention to potential environmental exposures is as important as attention to the reported diseases, not only because environmental pollution often is the reason of public concern and thus relevant for risk communication, but also for deciding about the boundaries of the population at risk. Moreover, environmental information is necessary for judgement of the plausibility of a causal relation and for advising measures to prevent exposure. Within this two-way approach, three stages are distinguished: orientation stage, verification stage and quantification stage. Only if an increased risk as well as an elevated exposure is verified, under certain conditions a case-control study may be useful to study causality between exposure and adverse health events. During all stages of the investigation, good risk communication strategies have to be taken into account. However, even then it might be difficult to prevent conflicts, because of the differing interests between experts and the community involved. One of the most important aspects that determine judgements about risks by threatened people, is controllability; that is why community participation is essential. Therefore it can be concluded that cluster management is a mutual endeavour for experts, public and media, where experts are judged on three characteristics: expertise, credibility and empathy.

Emergency exposure limits: a guide to quality assurance and safety.

Emergency exposure limits (EELs) are necessary in disaster prevention, preparation, and repression. Occupational EELs are available for many chemicals, but are of low toxicological adequacy. An animal experimental EEL of high toxicological adequacy available for many irritant chemicals is the concentration causing a 50% decrease in respiratory rate (RD50). The most outstanding EELs for the general population are the emergency response planning guidelines (ERPGs). A theoretical framework for a three-limit system is developed by the European Chemical Industry Ecology and Toxicology Center (ECETOC). ECETOC found over one order of magnitude variation between assessments of several companies. Nine selected EELs were classified in three clusters of increasing degrees of seriousness of health effects. There was little consistency within clusters, making it impossible to combine EELs. It is recommended to develop a toxicologically adequate EEL in an intercontinental context with cooperation of industry and (supra)national regulatory bodies. ERPGs can be taken as a start. The framework developed by ECETOC can be used to improve the limit setting procedure. A 5- to 10-year update should become part of the procedure. Attention should be devoted to the use of expert judgment. The minimal uncertainty in EELs should be expressed by presenting ranges instead of single values.