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Notes: Summary From 1979 to 1981, several medical surveys were carried out among a population living in the vicinity of a cement plant that emitted dust containing thallium until August, 1979. Air, soil, plants, and domestic animals in the area were contaminated by thallium and this led to an increased intake of thallium in the population, mainly due to the consumption of home-grown vegetables and fruit. In order to assess the degree of the individuals' exposure to thallium, thallium levels in 24-h urine samples (TIU) were determined. Three surveys were carried out from September to December, 1979 to assess the degree of thallium exposure of different parts of the general population. Subjects with relatively high exposure, as indicated by the results of the above mentioned population surveys, or those suffering from health disorders that might be related to an increased intake of thallium, were reexamined several times from 1979–1981. Special attention was also given to children attending a kindergarten situated about 0.5 km from the cement plant. As compared to an “unexposed” reference population (mean TIU: 0.3 μg/1), the majority of the population living in the cement plant area had significantly elevated urinary thallium levels (range: 〈 0.1–76.5 μg/1) indicating a substantially increased environmental exposure. A reduction of the intake of thallium was mainly achieved by the fact that the population, as advised by the authorities, largely avoided the consumption of home-grown, potentially contaminated food-stuffs. Reports on the teratogenicity of thallium in certain animal species caused great concern that thallium might have exerted teratogenic effects on the newborn of women exposed to thallium during pregnancy. Therefore, an investigation of children born between January, 1978 and August, 1979 (n = 297) was carried out. Although the number of congenital malformations was greater than expected, we conclude, considering carefully all data available, that there is likely no causal relationship between thallium and the occurrence of congenital malformations in the children investigated.

Notes: Summary In order to assess the degree of thallium exposure in a population living around a thallium emitting cement plant in a small city in North-West Germany thallium levels in 24 h urine samples of 1,265 subjects and in hair samples of 1,163 subjects were determined. Urinary thallium levels in two groups of subjects living in an urban and a rural area of West Germany were determined for reference. As compared to these subjects the population living around the cement plant exhibited obvious signs of increased thallium intake. The mean urinary thallium concentration was 2.6 μg/1 and ranged up to 76.5 pg/1. In contrast, the mean urinary thallium levels of the two reference groups were 0.2 and 0.4 μg/1, respectively. Hair thallium levels of the population living around the cement plant were also markedly increased (mean: 9.5 ng/g). The major route of the population's increased intake of thallium was found to be the consumption of vegetables and fruit grown in private gardens in the vicinity of the cement plant. As was shown by chemical analyses vegetables and fruit grown in these gardens were contaminated by thallium-containing atmospheric dust fall-out caused by emissions of the cement plant. The pulmonary route of uptake as well as other sources did not seem to play a significant role in the population's exposure to thallium. Polyneuritic symptoms, sleep disorders, headache, fatigue and other signs of psychasthenia were found to be the major health effects associated with increased thallium levels in urine and hair. No positive correlation was found between the thallium levels in hair and urine and the prevalence of skin alterations, hair-loss and gastro-intestinal dysfunctions.

Notes: Abstract Only weak oestrogenic activity has been reported for p-alkylphenols compared with the physiological hormone 17β-estradiol. Despite the low potency, there is concern that due to bioaccumulation oestrogenically efficient blood levels could be reached in humans exposed to trace levels of p-alkylphenols. To address these concerns, toxicokinetic studies with p-tert-octylphenol [OP; p-(1,1,3,3-tetramethylbutyl)-phenol] as a model compound have been conducted in male Wistar rats. OP blood concentrations were determined by GC-MS in rats receiving either single oral (gavage) applications of 50 or 200mg OP/kg body wt or a single intravenous injection of 5mg/kg body wt. The OP blood concentration was ∼1970ng/ml immediately after a single intravenous application, decreased rapidly within 30 min, and was no longer detectable 6–8h after application. The curve of blood concentration vs time was used to calculate an elimination half-life of 310min. OP was detected in blood as early as 10min after gavage administration, indicating rapid initial uptake from the gastrointestinal tract; maximal blood levels reached 40 and 130ng/ml after applications of 50 and 200mg/kg, respectively. Using the area under the curve (AUC) of blood concentration vs time, low oral bioavailabilities of 2 and 10% were calculated for the 50 and 200mg/kg groups, respectively. OP toxicokinetics after repeated administration was investigated in male Wistar rats receiving daily gavage administrations of 50 or 200mg OP/kg body wt for 14 consecutive days. Profiles of OP blood concentration vs time determined on day 1 and day 14 were similar, indicating that repeated oral gavage administration did not lead to increased blood concentrations. Another group of rats received OP via drinking water saturated with OP (∼8mg/l, corresponding to a mean daily dose of ∼800μg/kg) over a period of up to 28 days. OP was not detected in any blood sample from animals treated via drinking water (detection limit was 1–5ng/ml blood). OP concentrations were also analysed in tissues obtained from the repeated gavage (14 days) and drinking water groups (14 and 28 days). In the 50mg/kg group, low OP concentrations were detected in fat and liver from some animals at average concentrations of 10 and 7ng/g tissue, respectively. OP was not detected in the other tissues analysed from this group. In the 200mg/kg group, OP was found in all tissues analysed except testes (fat, liver, kidney, muscle, brain and lung had average concentrations of 1285, 87, 71, 43, 9 and 7ng/g tissue, respectively). OP was not detected in tissues of animals receiving OP via drinking water for 14 or 28 days, except in muscle and kidney tissue of one single animal receiving OP for 14 days. Using rat liver fractions it was demonstrated that OP was conjugated via glucuronidation and sulphation in vitro. A V max of 11.24 nmol/(min * mg microsomal protein) and a K m of 8.77μmol/l were calculated for enzyme-catalysed OP glucuronidation. For enzyme-catalysed sulphation, a V max of 2.85nmol/(minT15*mg protein) and a K m of 11.35μmol/l were calculated. The results indicate that OP does not bioaccumulate in rats receiving low oral doses, in agreement with the hypothesis of a rapid first-pass elimination of OP by the liver after oral ingestion, via glucuronidation and sulphation. Only if these detoxification pathways are saturated may excessive doses lead to bioaccumulation.