bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Alveolar Phospholipoproteinosis Induced by Orasol Navy Blue Dust
Authors: Ballantyne Bryan 
Published: December 2008

1 Orasol Navy Blue (ONB) is a water-insoluble nitroaromatic dye to which workers may be exposed to the dust. 2 Rats and guinea pigs exposed for 30 min to 173 mg m-3 did not show toxic signs or respiratory tract histopathology. 3 Rats, mice and guinea pigs were exposed 6 h a day for 20 or 100 days to 2.05 mg m-3 ONB dust (particle size, 33.6% < 5 μm). Except for decreased body weight of guinea pigs during the exposure period, no adverse signs were seen over a 1-year period from the first exposure. Respiratory tract histopathology was not seen in mice or guinea pigs. Rats showed scattered alveolar lesions characterized by aggregations of macrophages, PAS-positive debris, cholesterol, sudanophilia and birefringence, with preservation of the interstitium and no fibrogenic response. The number and size of these lesions was related to the duration of exposure. 4 The similarity of the lesions seen in the rat following exposure to ONB dust and those seen in humans from other exogenous causes of pulmonary alveolar phospholipoproteinosis suggests that overexposure of humans to a respirable dust of ONB may produce this lesion. 5 The rat is a convenient model to investigate pulmonary alveolar phospholipoproteinosis by exposure to respirable dusts.
Current Perspectives on Particulate Induced Pulmonary Tumours
Authors: Hext P.M. 
Published: December 2008

1 Chronic exposure to insoluble particulates can lead to the development of pulmonary tumours. These have been classified as broncho-alveolar or squamous/epidermoid according to their histopathological characteristics and have been reported in inhalation studies in rats of materials ranging from diesel exhaust and silica to titanium dioxide. 2 The sequence of changes within the rat lung leading to tumours has been characterised. It is apparent that one prerequisite is that the lung load of the particulate matter must exceed the normal clearance capacity, either by overloading the normal alveolar macrophage mediated mechanism or by induction of toxicity with materials such as silica. This results in inflammatory responses, including, or resulting in, epithelial hypertrophy and/or hyperplasia and squamous metaplasia. The persistence of these tissue responses over chronic time periods can lead to tumorigenesis. 3 Research into the mechanisms involved in the initiation and progression of both the inflammatory response and subsequent tumorigenic response to lung particulate loading is in progress. Impairment of macrophage function and mobility by inert particles constitutes one route by which this can arise, as does toxicity to this cell type by biologically reactive particles. At the molecular level, the role of inflammatory mediators, especially the cytokines, has received much attention. 4 Particulate induced lung tumours are perceived to be a phenomenon specific to the rat and their relevance to man is questionable.
Redtide in the Philippines
Authors: Hartigan-Go K. , Bateman D.N. 
Published: December 2008

1 Redtide is a marine phenomenon that poses great risk to the health and economic livelihood of people in coastal areas. Paralytic shellfish poisoning develops when a person consumes molluscs containing toxic dinoflagellates and suffers neurological and/or gastrointestinal manifestations. 2 Four redtide incidents in the Philippines are presented. The manner in which the problems were managed are described. 3 The clinical features of redtide poisoning in the Philippines included gastro-intestinal and neurological features with deaths secondary to ventilatory failure. Mortality ranged from 0% to 12% in the different redtide episodes. 4 There are many lessons to be learned in handling this kind of natural disaster. For an effective toxicovigilance programme, there must be a central co-ordinating responsible organization, a clear definition of roles and functions and good inter-agency co-operation. Appropriate surveillance procedures, resources to intensify surveillance at times of risks, prompt warning system, and the ability to impose bans on consumption are also necessary. 5 Poisons centres can play an important role during times of redtide. This may include toxicovigilant activities, such as early warning and educational campaigns to consumers, and seminars in the recognition and management of paralytic shellfish poisoning. 6 The contribution of the epidemiologists in investigating and monitoring the extent of public health damage and patterns of poisoning in a coastal community is emphasized.
Elemental Mercury Vapour Toxicity: Treatment and Levels in Plasma and Urine
Authors: Houeto P. , Sandouk P. , Baud F.J. , Levillain P. 
Published: December 2008

1 We report two cases of acute mercury vapour intoxication in humans. The mercury vapour was released from smelting alloys (gold-mercury amalgam). The alloy was apparently contaminated with an unknown amount of mercury. 2 Within half an hour of the incident, the victims began having moderate headache, nausea, lumbar pain and shortness of breath at rest. The patients were treated with BAL (2,3 dimercaptopropanol), followed by DMSA (2,3 dimercaptosuccinic acid). 3 Serial measurements of mercury metal in plasma and in urine were made for ten days. 4 The results suggest that in spite of the treatment, relatively high concentrations of mercury remain in the plasma for a very long time, and this could be explained by the progressive release of mercury from red blood cells and tissues after oxidation. However, BAL and DMSA did not seem to be the most efficient antidotes. They reduce the piasma inorganic mercury uptake at concentrations of <50 μg l-1.
Metabolism and Genotoxicity of the Halogenated Alkyl Compound Tris(2,3-Dibromopropyl)phosphate
Authors: van Beerendonk G.J.M. , Nelson S.D. , Meerman J.H.N. 
Published: December 2008

1 The genotoxicity of the flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) was studied in vivo. Results showed that Tris-BP was highly clasfogenic, but it could only initiate a low number of preneoplastic foci in the rat liver in vivo. In Drosophila, Tris-BP could be classified as a cross-linking agent, because it was more clastogenic than mutagenic. The use of completely deuterated Tris-BP as a metabolic probe revealed that cytochrome P450 and most likely the formation of 2-bromoacrolein (2BA) from Tris-BP is important for the observed genotoxic effects. 2 In contrast to the high mutagenicity of Tris-BP and 2BA in Salmonella typhimurium, we were unable to detect an increase in mutation frequency of 2BA on the hprt locus of human TK6 cell line. In another system, using a shuttle vector modified with 2BA:DNA-adducts, also no increase in mutation frequency could be detected in human cells. This low mutagenicity of 2BA corresponds with its low mutagenicity in Drosophila and its low induction of preneoplastic foci in the rat liver. 3 Several DNA adducts of 2BA have been identified, including an unstable 3-(bromooxypropyl)thymidine adduct which has the potential to form cross-links and a cyclic 3,N 4-(bromo)propeno-deoxycytidine adduct which can possibly be involved in the clastogenicity of Tris-BP. 4 Taken together, these data indicate that Tris-BP and 2BA may not effectively induce gene mutations in eukaryotic systems, but rather be potent clastogens. Risk assessment of these and related compounds should therefore be based on the knowledge of clastogens rather than mutagens.
Molecular Dosimetry of DNA Damage Induced by Polycyclic Aromatic Hydrocarbons; Relevance for Exposure Monitoring and Risk Assessment
Authors: Baan R.A. , Steenwinkel M.-J.S.T. , van den Berg P.T.M. , Roggeband R. , van Delft J.H.M. 
Published: December 2008

Polycyclic aromatic hydrocarbons (PAH) form a large group of organic chemicals that are widely distributed in our environment as pollutants of air, water and soil. Several PAH are carcinogenic in rodents, while exposure to these compounds has been associated with various types of human cancer. Upon entering the body, PAH may be converted into reactive electrophilic species, which can give rise to the formation of DNA adducts. DNA adduct formation is considered to be the initial event in chemical carcinogenesis. In this paper, two methods are illustrated that are widely used to determine PAH-DNA adduct formation, namely 32P-postlabelling, and immunochemical analysis with specific antibodies. The applications of the 32P-postlabelling assay comprise the following: - A study of interspecies differences in PAH bioactivation in vitro, with microsomal preparations isolated from liver tissue of various rodent species and of human origin; the results indicate that there are considerable qualitative differences between the adduct patterns obtained, which is relevant with respect to extrapolation from animal to man. - The analysis of DNA adduct formation in fish retrieved from marine environments polluted to various extents with PAH; results of these studies show a correlation between liver-DNA adduct levels in these fish and the degree of PAH contamination in the aquatic environment. - Biomonitoring of PAH exposure through analysis of adducts in blood cells obtained from heavy and light smokers; the data show a fair correlation between PAH-DNA adduct levels in white blood cells and cotinine content in blood plasma, the latter being used as a marker for exposure to cigarette smoke. The activity of the detoxifying enzyme glutathione S-transferase M (GSTM1) was also determined in these individuals. Immunochemical analysis with a benzo(a)pyrene(BP)-DNA-specific antiserum was used to investigate BP-adduct induction in situ, in different epithelial cell types—basal/non—basal cells—of hamster trachea exposed to BP in vitro, Histochemical staining of cell-specific cytokeratins was combined with adduct-specific immunostaining. The latter was quantified by immunofluorescence microscopy. The results show that removal of DNA adducts from the basal cells is more rapid during the first 24 h following exposure than from the non-basal cells. The sensitive methods for molecular dosimetry of DNA damage, as illustrated in this paper, appear suitable for determining exposure of animals and humans to PAH. Further animal experiments and in vitro model studies will provide useful additional information that will help evaluate the relevance of biomonitoring data with respect to the health risk that may be associated with the exposure.
Chemical gastro-oesophagitis, upper gastrointestinal haemorrhage and gastroscopic findings following Dettol poisoning
Authors: Chan Thomas Y.K. , Sung Joseph J.Y. , Critchley Julian A.J.H. 
Published: December 2008

1 Dettol liquid (chloroxylenol 4.8%, pine oil, isopropyl alcohol), a household disinfectant, has a corrosive action on the gastrointestinal mucosa when swallowed. The inci dence of upper gastrointestinal haemorrhage and gastro scopic findings following Dettol poisoning was studied in 89 patients. 2 Five patients (5.6%) developed minor haematemesis, in the form of coffee-coloured or blood-stained vomitus. One patient had a gastroscopy performed on the day after admission, showing signs of chemical burns in the oesoph agus and stomach. Gastroscopy was performed in one other patient on day 11 to rule out oesophageal stricture; the patient was normal. All patients completely recovered. 3 The data from this study suggest that upper gastroin testinal haemorrhage following Dettol poisoning tends to be mild and self-limiting. Gastroscopy, which may increase the risk of aspiration in patients with impaired consciousness, is not required unless other causes of gas trointestinal bleeding are suspected.
Therapeutic efficacy of sodium nitrite and 4-dimethylaminophenol or hydroxylamine co-administration against cyanide poisoning in rats
Authors: Bhattacharya R. 
Published: December 2008

1 The therapeutic efficacy of combined treatment of sodium nitrite (NaNO2) and 4-dimethylaminophenol (DMAP) or hydroxylamine (H2NOH) was investigated in potassium cyanide (KCN) intoxication in male rats.2 Therapy with NaNO2(0.27 mmol kg-1) + DMAP (0.09 mmol kg-1) or NaNO2+ H2NOH (0.09 mmol kg-1, produced a protection index (ratio of LD50of KCN in rats receiving therapy to an LD50of KCN in rats given only 0.9% saline) of 2.5 and 2.0 respectively.3 Both the regimens exhibited a beneficial effect in terms of improving the survival time and postural defects in rats exposed to 2 LD50KCN.4 NaNO2+ DMAP showed a significant protective effect in the disposition of the plasma cyanide level at different time intervals.5 The NaNO2+ DMAP regimen was superior to NaNO2+ H2NOH in terms of reactivating the inhibited brain cytochrome oxidase enzyme.6 The addition of sodium thiosulphate (Na2S2O3) in both the regimens increased the degree of protection.7 The results suggest that combined therapy with NaNO2+ DMAP could significantly reduce the toxic effects of cyanide, compared with NaNO2+H2NOH treatment.
High performance liquid chromatography with ultraviolet detection used for laboratory routine determination of fluvoxamine in human plasma
Authors: Belmadani A. , Combourieu I. , Bonini M. , Creppy E.E. 
Published: December 2008

Fluvoxamine is an antidepressant drug introduced into the clinic in 1986. It acts by selectively inhibiting neuronal serotonin recapture. It can be quantified by several meth ods, including high performance liquid chromatography. The HPLC method used so far needs special equipment and has poor sensitivity. The technique is difficult and time consuming. An easier, quicker and more sensitive HPLC assay for the routine determination of fluvoxamine in human plasma has therefore been developed. After alkalinisation and direct extraction by a mixture of n-hexane-isoamylic alcohol 985: 15 (v/v) of plasma samples, the organic phases were further extracted by HCl 0.1 N. Thirty μL of the final extract (with loxapine as internal standard) were injected directly into a C-8 column with a mobile phase consisting of 370 mL acetonitrile, 0.4 mL diethylamine, 630 mL of distilled water, 25 mL pic B5. UV detection at 254 nm was used. The whole process was completed in 40 min. The detec tion limit was 10 ng mL-1. No interference was found either with several benzodiazepines or with antidepres sant drugs commonly associated during treatments.
Preliminary in vitro investigation into the use of alkaline elution assay for the biomonitoring of humans exposed to genotoxic agents
Authors: Leroy Therese , Lison Dominique , Lauwerys Robert 
Published: December 2008

1 This in vitro study was undertaken as a preliminary approach before assessing whether the alkaline elution assay can be applied to peripheral blood lymphocytes (PBL) for the monitoring of humans exposed to genotoxic agents such as polycyclic aromatic hydrocarbons (PAH). We have compared in vitro, with the aid of the alkaline elution assay, the formation and the repair of DNA single- strand breaks (ssb) induced by different genotoxic agents [gamma-irradiation, ethyl methanesulfonate (EMS), benzo<a>pyrene diol epoxide (BPDE)] on quiescent and PHA-stimulated human lymphocytes and on a fibroblast cell line. 2 Gamma-irradiation (4 Gy) induced an equivalent amount of DNA ssb in the three cell types. On the other hand, after treatment with EMS (10mM) and BPDE (50μM), a higher production of DNA ssb was observed in replicat ing cells (PHA-stimulated lymphocytes and fibroblasts) when compared with quiescent lymphocytes. 3 After gamma-irradiation, all cell types repaired more than 65% of ssb within 1 h. After treatment with EMS, we noted a deficient DNA repair capacity in quiescent lym phocytes in comparison with replicating cells. In all cell types treated with BPDE, more breaks were observed after a 2 h repair period than immediately after treatment, demonstrating the involvement of a slow repair mecha nism after BPDE treatment. 4 Several conclusions can be drawn from this pilot study, (i) when assessing in vitro the induction and the repair of DNA lesions induced by chemicals, it seems rea sonable to test both non-replicating and replicating cells since their response may be different; (ii) in view of the relative persistence of DNA damage induced in vitro by BPDE in resting lymphocytes, chronic exposure to PAH could give rise to a certain accumulation of DNA damage in coke oven workers lymphocytes. Further studies will be necessary to determine whether these damages could be detected by alkaline elution.
Decorporation of thorium-228 from the rat by 3,4,3-LIHOPO and DTPA after simulated wound contamination
Authors: Stradling G.N. , Gray S.A. , Pearce M.J. , Wilson I. , Moody J.C. , Burgada R. , Durbin P.W. , Raymond K.N. 
Published: December 2008

1 With DTPA as a comparison, the siderophore analogue 3,4,3-LIHOPO has been examined for its ability to remove 228Th nitrate from the rat after subcutaneous (sc) and intramuscular (im) injection to simulate wound contamination. The commencement of treat ment was delayed 30 min, 6 h or 1 d and the animals killed at 7 d. 2 In all cases 3,4,3-LIHOPO was appreciably more effec tive than DTPA although the efficacy of treatment and the relative effectiveness of the ligands decreased rapidly with their delay in administration. 3 Optimum removal with both ligands occurred when initial local administration at 30 min after exposure was followed by repeated intraperitoneal injection at 6 h, 1, 2 and 3 d. Under these conditions the body con tent of 228Th was reduced to 20% of controls after sc injection and 15% after im injection. The correspond ing values using repeated DTPA administration were 80% and 54%. 4 It is concluded that 3,4,3-LIHOPO represents, poten tially, a considerable advance on DTPA, the current agent of choice for the treatment of wounds contami nated by 228Th.
Setting air quality standards for carcinogens: an alternative to mathematical quantitative risk assessment — discussion paper
Authors: Maynard R.L. , Cameron K.M. , Fielder R. , McDonald A. , Wadge A. 
Published: December 2008

1 It has been accepted in many countries that the regula tion of ambient air quality should involve the use of health-based air quality standards. 2 Setting standards for air pollutants which are genotox ic carcinogens presents difficult problems to the regu lator, in that the prediction of the effects on health of low levels of exposure is suspected to be inaccurate, and is not presently amenable to either experimental or epidemiological verification. 3 In some countries, techniques of Mathematical Quantitative Risk Assessment (MQRA) have been adopted to calculate acceptable levels of exposure to, or the unit risk factors for, genotoxic carcinogens. We regard these approaches as unsatisfactory. 4 An alternative approach, based upon a number of argued premises, a strategy which identifies decision points and the cautious application of uncertainty fac tors, is described.
Effects of variation in detoxification rate on dose monitoring through adducts
Authors: Föst U. , Törnqvist M. , Leutbecher M. , Granath F. , Hallier E. , Ehrenberg L. 
Published: December 2008

1 Föst et al. ( Human & Experimental Toxicology 1991; 10: 25) have shown that ethylene oxide (EO) added to human blood gave rise to a higher level of adducts to haemoglobin (Hb) when the donors were deficient in an erythrocytic glutathione S-transferase (GST, later found to be GST-theta) than in blood from persons pos sessing this enzyme, and drew the conclusion that this polymorphism in detoxification rendered Hb adducts less suitable for biological monitoring. 2 By fitting a kinetic model to the data, the present study shows that the Hb adduct level gives a correct measure of the dose (concentration integrated over time) rele vant to risk estimation. 3 It does illustrate, however, the importance of knowing an individual's detoxification efficiency, when Hb adduct measurements are used to assess environmen tal exposure, for example in occupational surveillance.
A stepwise procedure for evaluating irritant materials in normal volunteer subjects
Authors: Dykes P.J. , Black D.R. , York M. , Dickens A.D. , Marks R. 
Published: December 2008

1 The cutaneous response to a known irritant has been assessed in human volunteer subjects using both clini cal scoring and two non-invasive instrumental meth ods ; erythema measurement using an erythema meter and capillary blood flow using a laser Doppler device.2 Aqueous solutions (0.5% and 1%) of sodium hydroxide were applied to back skin for 3, 15 and 60 min with assessments immediately after removal and at 1, 24 and 48 hours.3 Increased erythema was seen with increasing duration of exposure and an increase was also seen at 1 h, 24 h and 48 h after removal of the patch. The results obtained with the erythema meter paralleled the clini cal erythema scores. However, the laser Doppler device showed the greatest changes immediately after removal of the patch with subsequent readings show ing a gradual decrease.4 Statistical analysis of the data has been carried out to determine the accuracy and precision of the assess ment procedures and to determine the minimum test panel size for detecting irritant reactions.5 Comparison between back and forearm skin indicated a greater sensitivity to sodium hydroxide on the back.6 The results of this study define an ethical approach to testing irritant materials in human subjects and pro vide the basis for the development of a classification system for cutaneous irritants.
Persistence of sodium monofluoroacetate in rabbits and risk to non-target species
Authors: Gooneratne S.R. , Eason C.T. , Dickson C.J. , Fitzgerald H. , Wright G. 
Published: December 2008

1 Sodium monofluoroacetate (1080), a vertebrate pesti cide used in New Zealand, was administered orally to rabbits at two dose levels (sub-lethal and lethal) to determine how long 1080 would persist in plasma, liver, kidney, and muscle so that the risk of consump tion of meat from lethally or sub-lethally poisoned rab bits by non-target species could be assessed.2 The plasma elimination half-life in rabbits receiving a sub-lethal dose was 1.1 h. Retention of 1080 in tissue was greater in rabbits dosed with a lethal dose than in those that received a sub-lethal dose. Irrespective of the dose level, concentration of 1080 in muscle, kidney, and liver was substantially lower than in the plasma.3 Poisoning of dogs is possible because of their extreme susceptibility to 1080. Poisoning of birds is less likely. The risk of secondary poisoning is reduced as the con centration of 1080 declines in putrefying carcasses.
Effects of a protein kinase C inhibitor, Ro 31-7549, on the activation of human leuko cytes by particulate stimuli
Authors: Ruotsalainen Marjo , Savolainen Kai M 
Published: December 2008

1 A new specific protein kinase C (PKC) inhibitor, Ro 31- 7549, was used to explore the mechanisms by which particulate stimuli, quartz and chrysotile, stimulate human polymorphonuclear leukocytes (PMNL) to pro duce reactive oxygen metabolites (ROM). Also soluble stimuli, formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and phorbol myristate acetate (PMA) were used. 2 Ro 31-7549 inhibited chrysotile-induced free intracellu lar calcium ([Ca2+]i) elevations but did not have an effect on quartz-induced elevations of [Ca2+] i. Both quartz and chrysotile induced production of ROM were partially inhibited by Ro 31-7549. fMLP-induced elevation of [Ca2+]i was inhibited by Ro 31-7549 whereas PMA did not affect [Ca2+]i. Ro 31-7549 strongly inhibited fMLP- induced ROM production, and completely abolished that induced by PMA. 3 These results suggest that PKC may have an important role in the activation of PMNL to produce ROM by par ticulate and soluble stimuli. However, the inhibition of chrysotile-, but not of quartz-induced [Ca2+]i elevations by Ro 31-7549 provides evidence that both PKC-depen dent and -independent mechanisms may play a role in the activation of human leukocytes to produce ROM.