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Notes: Abstract Fast transport kinetics of 51Cr (VI) into red blood cells (RBCs) in vitro were studied. No significant species differences were found between RBCs of man and rat. The uptake of 51Cr (VI) by RBCs in whole blood was composed of two different first order processes of different velocities (apparent t1/2 of 22.7 s and 10.4 min for man and 6.9 s and 10.1 min for rat, respectively). However, even after longer time periods a fixed portion of approximately 15% of the administered dose remained in the plasma and did not penetrate into RBCs Over the entire concentration range studied (10 μM–50 mM), the fast initial uptake followed Michaelis-Menten kinetics. The maximal capacity of this Cr(VI) transport into RBCs of man and rat was 3.1×108 CrO4 2− ions × cell−1 × min−1 and 2.5×108 CrO4 −2 ions × cell−1 × min−1, respectively. It is likely that Cr(VI) is transported into RBCs via a physiological anion carrier (“band-3-protein”).

Notes: Abstract Inhalation pharmacokinetics of dichlorofluoromethane (CFC 21) and chlorodifluoromethane (CFC 22) were studied in male Wistar rats by use of a closed inhalation chamber system. CFC 21 was readily eliminated via metabolism. However, CFC 22 underwent no detectable metabolism; pretreatment of the rats with DDT or phenobarbital did not stimulate metabolic transformation of the compound. Hence, formation of biologically relevant amounts of reactive intermediates from CFC 22 as a mechanism of toxicity seems unlikely.

Notes: Abstract Acrylic acid (AA), ethyl acrylate (EA) and n-butyl acrylate (BA) are widely used in the production of plastics, coatings and acrylic fibres. Occupational exposure occurs primarily via inhalation and/or skin contact. In chronic inhalation experiments EA and BA did not induce neoplastic changes in rats and mice (Klimisch and Reininghaus 1984; Miller et al. 1985). Additional investigations showed that AA and BA were not carcinogenic in mice after chronic dermal application (De Pass et al. 1984). However, recently other authors reported a weak carcinogenic potential of AA and BA after chronic dermal administration to mice (Cote et al. 1986). The conditions of the latter study lead to the suggestion that the observed tumours had developed secondarily due to the local irritating and corrosive properties of AA and BA. This view is supported by the negative results of AA, EA and BA in the conventional Ames test (Waegemaekers and Bensink 1984). Mutagenicity data in mammalian cell systems of EA were equivocal (Henschler 1986) and were lacking for AA and BA. For this reason the mutagenic potential of AA and BA was investigated in Syrian hamster embryo fibroblasts (SHE cells). DNA repair (UDS assay), chromosomal changes (micronucleus assay) and morphological transformation were chosen as biological endpoints.

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.

Notes: Abstract We report on a 30-month-old previously healthy Turkish boy who presented with fever, hepatosplenomegaly and generalized lymphadenopathy. He died 4 months after admission in spite of treatment with steroids, acycloguanosine and cyclophosphamide. Epstein-Barr virus (EBV) DNA was detected in the patient's bone marrow and in a lymph node biopsy. Cells from the lymph node biopsy showed monoclonal rearrangements of immunoglobulin heavy chain genes but no rearrangements of T-cell receptor β-chain genes or immunoglobulin kappa chain genes. Serological data indicated chronic active EBV infection. There was a slight increase of CD8 positive cells in peripheral blood and a normal response to T-cell mitogens. However, T-cell lines established with interleukin 2 from lymph node biopsy completely failed to kill autologous EBV-transformed B-cells and K 562 target cells. Moreover, in regression tests the patient's peripheral blood mononuclear cells completely failed to limit outgrowth of autologous EBV infected B-cells. We conclude that the patient's selective immunodeficiency had led to the rapid development of EBV-associated monoclonal lymphoproliferation.

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.