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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.

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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.