bluuebunny/crossref_metadata_2025 huggingface dataset:
In-Vitro Mechanisms of 1,2-Dichloropropane Nephrotoxicity using the Renal Cortical Slice Model
Authors: Trevisan Andrea , Meneghetti Paola , Maso Stefano , Troso Ornella
Published: December 2008

1 Renal cortical slices isolated from the kidneys of male Wistar rats were used as an experimental model for studying the nephrotoxicity induced by 1,2-dichloropropane.

2 The solvent causes a depletion of renal reduced glutathione content and slight, but significant, lipid peroxidation. The block of the oxidative pathway with carbon monoxide prevents glutathione content depletion, and shows that this conjugation is the major step in 1,2-dichloropropane metabolism.

3 Loss of organic anion accumulation and release into the incubation medium of tubular enzymes, mainly from the soluble fraction, are the toxic effects of the solvent. The brush border is only slightly affected.

4 The mechanism of nephrotoxicity appears to occur via mercapturic acid metabolism. Acivicin and aminooxyacetic acid, inhibitors of gammaglutamyltransferase and β-lyase activity, respectively, partially but significantly prevent the loss of organic anion accumulation induced by 1,2-dichloropropane. Furthermore, α-ketobutyrate, an activator of β-lyase, enhances the effects of 1,2-dichloropropane on the target, but is itself toxic for organic anion accumulation.
Effect of Ingestion and Inhalation of Lead on the Reproductive System and Fertility of Adult Male Rats and their Progeny
Authors: Pinon-Lataillade G. , Thoreux-Manlay A. , Coffigny H. , Monchaux G. , Masse R. , Soufir J-C.
Published: December 2008

Ninety-day-old Sprague-Dawley rats were intoxicated for 70 d with lead, given either as 0.3% lead acetate in drinking water or by inhalation as 5 mg m-3 lead oxide. Direct or transmitted lead toxicity for the male reproductive system was assessed in the rats and their offspring from pituitary and genital organ weights after exposure, the numbers of Sertoli and germ cells, the number, motility and morphology of epididymal spermatozoa, the levels of plasma testosterone, LH and FSH and fertility tests. Whole blood lead levels were similar after lead ingestion and after inhalation (58.0 ± 1.7 μg dl-1 vs. 51.1 ± 1.8 μg dl-1). Lead acetate ingestion did not affect the reproductive system or fertility of rats. Inhalation of lead oxide did not affect fertility either, but seminal vesicle weight dropped significantly, which might suggest an alteration in the pattern of testosterone secretion. In the male progeny of sires that inhaled lead, the number of epididymal spermatozoa decreased but this did not interfere with fertility. Our results show that for the doses studied, lead inhalation and lead ingestion do not produce strikingly different effects on the male rat's reproductive system. Differences between the present findings and those of others might be due to difference of rat strain or of age at exposure.
Selective Inhibition of Gastrointestinal β-Glucuronidase by Polyvinylbenzyl D-glucaro(1,4)lactonate: Attachment of D-Glucaro(1,4)lactone to Polyvinylbenzyl Chloride
Authors: Sacco C. , McEwen W.E. , Calabrese E.J.
Published: December 2008

D-Glucaro(1,4)lactone, a potent β-glucuronidase inhibitor was attached via the carboxylic acid moiety to polyvinylbenzyl chloride (PVBC) using a bimolecular nucleophilic displacement reaction, First, the caesium salt of D-glucaro(1,4)lactone was prepared by titrating the carboxylic acid to neutrality with aqueous caesium bicarbonate. The polyvinylbenzyl D-glucaro(1,4)lactonate was obtained in maximum yields of between 50 and 60% when caesium D-glucaro(1,4)lactonate was incubated with PVBC in DMF at 50°C for 7 d in the presence of a catalyst, caesium iodide.
Efficacy of Dimercapto Chelatin Agents for the Treatment of Poisoning by Percutaneously Applied Dichloro(2-chlorovinyl)arsine in Rabbits
Authors: Inns R.H. , Rice P.
Published: December 2008

The efficacy of three chelating agents, BAL, DMPS and DMSA has been evaluated in rabbits as treatments for systemic dichloro(2-chlorovinyl)arsine [lewisite] poisoning by the percutaneous route. Chelating agent treatment reduced the incidence and severity of pathological liver changes following lewisite poisoning. There was no marked difference between the three chelating agents for protection against lethality when screened at an equimolar dose of 40 μmol kg-1. The results indicated DMPS and DMSA may prolong survival time compared with BAL.

The low toxicity of DMPS and DMSA compared to BAL enabled doses of 160 μmol kg-1 on a more prolonged dosing schedule to be used for DMPS and DMSA. This schedule showed DMPS and DMSA to give a significant improvement in protection against the lethal effects of percutaneous lewisite compared to that of BAL.

It was concluded that DMPS and DMSA have significant advantages over BAL for use as treatment for systemic lewisite poisoning.
Evaluation of a New Chelating Agent for Cadmium: A Preliminary Report
Authors: Gulumian M. , Casimiro E. , Linder P.W. , Rama D.B.K. , Hancock R.D.
Published: December 2008

The Plasma Mobilizing Index parameters of the newly synthesized chelating agent THP-12-ane N4, determined by computer simulation studies, have indicated that this chelating agent might be a good antagonist for cadmium intoxication. Experiments conducted on rats confirmed this observation and showed that THP-12-ane N4 might have the ability to chelate and mobilize cadmium in vivo.
Modulation of Biochemical and Cytological Profile of Bronchoalveolar Lavage Constituents in Rats Following Split-Dose Multiple Inhalation Exposure to Methyl Isocyanate
Authors: Gupta G.S.D. , Bajpai R. , Kaw J.L. , Dutta K.K. , Ray P.K.
Published: December 2008

1 Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l -1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure.

2 In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride. The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity.

3 In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF. The phagocytic potential of macrophages was, however, also decreased under this regime.
In Vitro and In Vivo Adsorption Stud ies of Diazinon
Authors: Orisakwe O.E. , Obi N.
Published: December 2008

The in vitro and in vivo adsorption of diazinon to two brands of activated charcoal and locally produced carbon black (N220) has been studied. Solutions of diazinon 10, 20 and 40 μg ml-1 were prepared in distilled water and different quantities of adsorbent added. Diazinon-adsorbent slurries were vortex mixed, centrifuged and analysed for free diazinon spectrophotometrically at 241 nm. Small quantities of activated charcoal (AC) and carbon black (CB) showed little or no adsorption of diazinon, while 1000 mg of either AC or CB was able to take up more than 70% at all concentrations of diazinon tested. In acute toxicity tests in mice the optimal adsorbent: diazinon ratio was 8:1 when the animals were treated with 45 mg kg-1 diazinon after immediate, 1, and 3 h post administration of the adsorbent.
Assessment of the Haemolytic Activity of 2-Butoxyethanol and its Major Metabolite, Butoxyacetic Acid, in Various Mammals Including Humans
Authors: Ghanayem Burhan I. , Sullivan Chantal A.
Published: December 2008

2-Butoxyethanol (BE) is a glycol ether produced in volumes exceeding 335 million pounds/year for industrial and domestic uses. BE causes acute haemolytic anaemia in rats and some other mammals. While BE is inactive in vitro, 2-butoxyacetic acid (BAA) is a potent haemolytic agent in vivo and in vitro. This finding suggests that metabolic activation of BE to BAA is required for haemolysis of erythrocytes to occur in vivo. Haemolysis of red blood cells (RBC) by BAA is preceded by swelling (increased mean cell volume [MCV] and haematocrit [HCT]). In an attempt to assess the potential risk to humans exposed to BE, studies were designed to determine the in vitro effect of BAA on RBCs from 10 mammalian species including humans. Blood samples from each mammalian species (n=3-5) were incubated with BAA at a final concentration of 0 (vehicle), 1 or 2 mM and kept at 37°C in a gently shaking water bath. Complete blood counts (CBCs) were measured at 0, 1, 2 and 4 h. BAA caused a time- and concentration-dependent increase in MCV and HCT of blood from rats, mice and hamsters (rodents), rabbits (lagomorphs), and baboons (primates). In contrast, blood from pigs (artiodactyis), dogs and cats (carnivores), guinea pigs (rodents/marsupials), and humans (primates), was minimally affected by BAA. These results were confirmed in guinea pigs and rats in vivo. Gavage administration of BE (250 mg kg-1) to rats resulted in increased MCV and HCT followd by haemolysis (decreased RBCs). Identical treatment with BE resulted in no significant change in these parameters in guinea pigs. These data clearly demonstrated that BE-induced haemolytic anaemia is species-dependent. This information may prove important for selecting appropriate animal models for use in the assessment of the health risk to humans exposed to BE. Future studies will focus on the cellular basis of the differential sensitivity of RBCs from various mammals to BAA.
The Biokinetics of Plutonium-239 and Americium-241 in the Rat After Subcutaneous Deposition of Contaminated Particles from the Former Nuclear Weapons Site at Maralinga: Implications for Human Exposure
Authors: Harrison J.D. , Hodgson A. , Haines J.W. , Stather J.W.
Published: December 2008

As an input to dose assessments, measurements have been made of the clearance of Pu and Am after subcutaneous implantation in rats for six particulate materials and one dust from the Maralinga test sites. The tissue distribution of Pu and Am were measured in groups of six animals at one month and 6 months after implantation. In addition, in vitro solubility tests were carried out on eight different particulate materials. Histological examination of the subcutaneous implantation site was undertaken after one year for selected materials. Autoradiographs of tissue sections showed that particles were surrounded by fibrotic tissue with macrophage and polymorphonuclear cell infiltration, the normal tissue response to foreign materials. The clearance data have been used to make estimates of the likely range in potential radiation doses in humans. To calculate the dose from dissolved 239Pu and 241Am, four different situations have been considered. For the dust, the results suggest that dissolution essentially ceases after the removal of Pu and Am from the surfaces of dust particles. From the values obtained, the acute release of a fraction of 10-2 of both nuclides from a dust contaminated wound was assumed. For a number of particles the results suggested continued dissolution and the clearance of 10-3 per year of both nuclides, continuing for a number of years, has therefore been considered. For the least soluble particles, there was no clear evidence of continued clearance and the acute release of 10-4 has therefore been taken as a lower estimate for dose calculations. To calculate radiation doses to lymphatic tissue the data were taken to suggest that, in general, a fraction of between 10 -2 and 10-4 may be translocated to the lymphatic system each year.
Effect of Aggressive Haemoperfiusion on the Clinical Course of Patients with Paraquat Poisonin
Authors: Suzuki Kouichiro , Takasu Nobukatsu , Okabe Toru , Ishimatsu Shinichi , Ueda Akinori , Tanaka Shigeru , Fukuda Atsuhiro , Arita Seizaburo , Kohama Akitsugu
Published: December 2008

The effect of aggressive haemoperfusion; i.e. haemoperfusion of 10 h or more during the first 24 h after ingestion, on the clinical course of paraquat poisoning was studied. Among 40 patients admitted within 15 h after ingestion of paraquat with an SIPP of less than 100 (h x μg ml-1), 21 received aggressive haemoperfusion and 19 received conventional haemoperfusion; i.e. haemoperfusion of less than 10 h during the same period. Survival rates of patients with severity between an SIPP of 100 and Proudfoof's curve in the two groups were compared by the log-rank test. Aggressive haemoperfusion did not improve the outcome but did improve the survival rates; that is, the number of patients surviving at particulalr points in time (P<0,05). The length of haemoperfusion for the aggressive haemoperfusion group was longer than that for the conventional group on the first day (P<0.001 ), but the difference was insignificant during the following two days. Neither the time from ingestion to haemoperfusion, urine volume from the first to third day, nor initial plasma-paraquat concentrations and SIPP were significant between groups. These findings imply that aggressive haemoperfusion reduces the severity of paraquat poisoning and elongates survival time. We, therefore, propose that the efficacy of more aggressive haemoperfusion, such as the 'continuous haemoperfusion' proposed by Okonek et al., should be further studied.
Cysteine Conjugate Toxicity in a Human Cell Line: Correlation with C-S Lyase Activity in Human Hepatic Tissue
Authors: Buckberry Lorraine D. , Blagbrough Ian S. , Nicholas Shaw P.
Published: December 2008

C-S lyase enzymes catalyse the generation of mutagenic and/or cytotoxic thiols from cysteine conjugated xenobiotics. These cysteine conjugates are produced subsequent to glutathione conjugations as a metabolic step in the mercapturic acid pathway, traditionally thought of as a pathway solely associated with detoxification. Human Chang liver (HCL) cells were challenged with a range of cysteine conjugates demonstrated to be substrates for human hepatic C-S lyases. The cellular toxicity of these compounds was determined and it was observed that the rank order of substrate toxicity obtained for the HCL cells followed the rank order of C-S lyase activity of the substrates in a freshly isolated mitochondrial fraction of human tissue. The presence of C-S lyase activity was also established in this cell line.
Monitoring of Total Chromium in Rat Fluids and Lymphocytes Following Intratracheal Administration of Soluble Trivalent or Hexavalent Chromium Compounds
Authors: Gao M. , Levy L.S. , Braithwaite R.A. , Brown S.S.
Published: December 2008

1 Intratracheal instillation of sodium dichromate (CrVI) and chromium acetate hydroxide (CrIII) to male Wistar rats gave rise to increased chromium concentrations in whole blood, plasma and urine up to 72 h post exposure; peak concentrations were reached at 6 h after exposure.

2 The ratio of whole blood chromium to plasma chromium concentrations was significantly different for Cr(VI) and CR(III) treatments. Both blood chromium and plasma chromium assays should therefore be used for the assessment of chromium exposure.

3 Chromium was also detected in peripheral lymphocytes. Cr(VI), but not Cr(lll) accumulated significantly in the lymphocytes after treatment. These cells have potential to be used for biomarkers of the assessment of exposure to chromium compounds.
A Study of Self Poisoning with Oral Salbutamol - Laboratory and Clinical Features
Authors: Lewis L.D. , Essex E. , Volans G.N. , Cochrane G.M.
Published: December 2008

1 The recent increase in asthma mortality coupledwith reports of fatal asthma associated with beta- 2-agonist therapy, has stimulated interest in the plasma concentrations of beta-2-agonists that produce systemic toxicity.

2 We prospectively studied 17 patients (9 male),mean age 23 years (range 2-72), who attendedthe emergency departments of hospitalsthroughout the United Kingdom having recently ingested an overdose of salbutamol.

3 Clinical, laboratory, ECG data, plasma and urine samples were obtained from each patient. Plasmawas assayed for salbutamol concentration using ahigh performance TLC-photodensitometric method.

4 The mean (± s.d.) salbutamol dose reported to have been ingested was 89(+83)mg and the mean plasma salbutamol concentration was 166 (range 18-449) ng ml potassium was 2.9 (s.d.±0.6) mM (n=16). None of-1. The mean plasma the patients in this study developed serious cardiac dysrrhythmias.

5 There were significant correlations between the plasma salbutamol concentration and plasma potassium concentration (r=-0.85; P<0.00005) and between plasma salbutamol concentration and pulse rate ( r=0,66; P<0.005).

6 We conclude that in these patients, without respiratory decompensation, suprapharmacological plasma concentrations ofsalbutamol were tolerated without serious cardiac arrhythmias or any fatalities.
Aging and Spontaneous Reactivation of Human Plasma Cholinesterase Activity After Inhibition by Organophosphorus Pesticides
Authors: Mason H.J. , Waine E. , Stevenson A. , Wilson H.K.
Published: December 2008

The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reactivation are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37°C and 22°C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37°C and 22°C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37°C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37°C.
In Vitro Studies on the Metabolism of Antipyrine in the Pig and Rat: with Special Refierence to Veterinary Medicine Licensing
Authors: Sainz-Pardo Clares Luis A. , Shaw Ian C.
Published: December 2008

Preparation of product licence applications for veterinary medicines requires metabolic studies in the target species. This experimental procedure uses animals and is costly. In the present report of preliminary studies it is demonstrated that pig liver homogenates prepared from abattoir material and homogenates of rat liver show the interspecies metabolic differences that would be expected in vivo. The results therefore support the use of abattoir-derived liver homogenates in preliminary studies to investigate target species metabolism in veterinary drug development.
Omeprazole overdose
Authors: Ferner R.E. , Allison T.R.
Published: December 2008

The clinical features and pharmacokinetics of omeprazole in overdose have not previously been described. We report 2 cases. The major clinical features were flushing, tachycardia and headache. Omeprazole pharmacokinetics remained unchanged in overdose.
Increased Incidence of DNA Double-strand Breaks and Anti-ds DNA Antibodies in Blood of Workers Occupationally Exposed to Asbestos
Authors: Marczynski B. , Czuppon A.B. , Marek W. , Reichel G. , Baur X.
Published: December 2008

Asbestos, proven to be carcinogenic in humans and animals, is reported to have no genotoxic effect. Asbestos workers have an increased risk of lung cancer, mesothelioma, and other tumours. Earlier findings showed that crocidolite can induce DNA strand breaks in cultured rat embryo cells as assessed by nick translation.

We investigated DNA double-strand breaks in white blood cells (WBC) of ten workers occupationally exposed to asbestos. According to our results, obtained with neutral filter elution, individuals who had been exposed to asbestos fibres showed two to four times more DNA double-strand breaks (dsb) in white blood cells than ten non-exposed persons. The induced DNA fragments are of about 250 kb (compared to chromosomal DNA of Saccharomyces cerevisiae standard marker).

Using additionally the chromosomal DNA protective method of agarose-plugs, DNA fragments in the range of 200 to 1000 kb have been found in the white blood cells of the same ten workers occupationally exposed to asbestos. In the white blood cells of non-exposed subjects no DNA fragments could be detected with this method.

Compared to 51 non-exposed persons, elevated anti-ds DNA antibody concentrations were found in ten workers occupationally exposed to asbestos. The fact that workers occupationally exposed to asbestos have distinctly more double-strand breaks and anti-ds DNA antibodies could mean that an increased incidence of DNA-fragments may be an important indicator in the chronic effect of asbestos-associated carcinogenesis. Apparently, the chronic effects of asbestos observed here do not seem to be identical with that of previously reported acute in vitro effects.
Mercury Kinetics in a Case of Severe Mercuric Chloride Poisoning Treated with Dimercapto-1-propane Sulphonate (DMPS)
Authors: Toet A.E. , van Dijk A. , Savelkoul T.J.F. , Meulenbelt J.
Published: December 2008

1 A case of severe mercuric chloride poisoning with clinical signs of mucosal damage of the gastrointestinal tract and anuric renal failure, is presented. The initial whole blood mercury concentration was 14,300 ?g 1-1. This concentration is supposed to be associated with fatal outcome due to multiple organ failure.

2 Because of anuric renal failure, haemodialysis was necessary. Kidney function returned to normal within 10 days. Haemodialysis proved to be ineffective with regard to total mercury elimination.

3 Treatment with DMPS was started because of very severe poisoning, anuric renal failure and optimistic reports on the 'new' chelating agent 2,3-dimercapto-1-propanesulphonic acid (DMPS) in mercury poisoning. DMPS was administered by parenteral route initially and was continued thereafter by oral route, until whole blood and urine mercury concentrations had decreased below a level considered as toxic. Except for a temporary pruritic erythema of the skin, no side effects of DMPS treatment were observed.

4 The clinical course was mild, despite continuing high whole blood mercury concentrations, Recovery was uneventful and complete. DMPS treatment, administered by intravenous and oral route, was shown to be an effective alternative for BAL in life-threatening mercuric chloride intoxication.

5 The pharmacokinetic data presented in this case report suggest that non-renal mercury clearance may considerably exceed renal mercury clearance.
Household Chemicals Poisoning Admissions in Zimbabwe's Main Urban Centres
Authors: Nhachi C.F.B. , Kasilo O.M.J.
Published: December 2008

1 A retrospective analysis to evaluate the epidemiology of poisoning by household chemicals based on admissions at Zimbabwe's six main urban hospitals over a 10-year period (1980-1989) was performed.

2 A total of 1192 household chemicals poisoning cases were recorded, and this constituted 20% of all poisoning cases (6018) recorded during the study period.

3 The 0-5 year age group constituted the majority of cases (61.3%), then the 16-25 and 26-30 year age groups accounting for 11 % and 5.2% respectively.

4 The sex distribution showed that 43.7% were females.

5 Most incidences were accidental (66.8%). Suicides and/or parasuicides accounted for 19%.

6 Mortality was recorded at 13% and most of the deaths were suicides.

7 Paraffin (Kerosene) was the most common poisoning agent accounting for 68% of the cases. This was followed by rat poisons (5.8%), bleaches (5.1 %) and caustic soda (3.3%).

8 The incidence of poisoning with household chemicals could be reduced by health education directed to parents emphasising the importance of safe storage of paraffin and other household chemicals, and by legislation to stop retailers selling paraffin for domestic use in second-hand containers.
Food Poisoning Admissions in Referral Hospitals in Zimbabwe: A Retrospective Study
Authors: Kasilo Ossy M.J. , Nhachi Charles F.B.
Published: December 2008

1 A ten-year (1980-1989) retrospective study of poisoning admissions due to food poisoning at six referral hospitals in urban Zimbabwe revealed 487 cases. This constituted 8.1 % of all poisoning admission cases (6018).

2 The majority of patients were among the 2.1-5 (20%), 5.1-10 (16%) and 21-30 (15%) year age groups in that descending order.

3 The agents implicated in food poisoning were mushrooms (47%), food-borne and other food-related toxins (37%), Elephants Ear (10%), alcohol (7%) and cassava (1 %).

4 The majority of poisoning cases were accidental, accounting for 99% of the total.

5 The treatment regimens mostly used included agents for correcting fluid and electrolyte imbalance (22.1 %), antibiotics (16.7%) and supportive measures (15.5%).

6 Mortality was recorded at 2.5% and the main agents associated with fatality were food-related toxins (5 cases), mushrooms (4 cases) and alcohol (4 cases).

7 The prevention and treatment of poisoning caused by food poisoning is mandatory in the effort to reduce poisoning caused by these agents.
Persistence of Sodium Monofluoroacetate in Livestock Animals and Risk to Humans
Authors: Eason C.T. , Gooneratnel R. , Fitzgerald H. , Wright G. , Frampton C.
Published: December 2008

1 Sodium monofluoroacetate (1080), a vertebrate pesticide widely used in New Zealand, was administered orally to sheep and goats at a dose level of 0.1 mg kg-1 body weight to assess risk to humans of secondary poisoning from meat. Blood, muscle, liver, and kidney were analysed for 1080 residues.

2 The plasma elimination half-life was 10.8 h in sheep and 5.4 h in goats. Concentrations of 1080 in muscle (0.042 ?g g-1), kidney (0.057 ?g g-1), and liver (0.021 ?g g-1) were substantially lower than those in plasma (0.098 ?g m-1) at 2.5 h after dosing.

3 Only traces of 1080 (<0.002 to 0.008 ?g g-1) were found in sheep tissues after 96 hours.

4 Livestock are normally excluded from areas where 1080 is being used for pest control, reducing the risk of secondary poisoning. Even with accidental exposure to a sublethal dose 1080 would not persist in tissues for more than a few days because it is cleared rapidly from the body. Therefore the occurrence of 1080 in meat intended for human consumption is highly unlikely.
Interaction between Ethanol and Opioids in a Protozoan Assay
Authors: Changhao Wu  , Henry J.A.
Published: December 2008

Ethanol excess combined with opioids can be fatal due to their toxic interaction, yet the nature of the interaction is little documented. Since ethanol and some opioids have membrane stabilizing activity, the present study used a protozoan motility model to test the possibility that ethanol may interact with some opioids on this basis. The EC50in motility reduction for ethanol, dextropropoxyphene, methadone and pethidine was 522.0± 36.7 mM, 0.59± 0.08 mM, 0.40± 0.09 mM and 4.57± 0.36 mM, respectively. When ethanol was combined with one of the three drugs in equitoxic doses at a ratio of 0.5:0.5, the predicted/observed EC50values for ethanol-dextropropoxyphene, ethanol-methadone and ethanol-pethidine were 1.37, 1,11 and 1.00, each being close to unity, indicating an additive interaction. The interaction between ethanol and dextropropoxyphene was further explored at 0.25:0.75 and 0.75:0.25 equitoxic dose ratios, with the predicted/observed EC50values of 0.98 and 0.97, also showing an additive interaction. This suggests that a non-specific interaction between ethanol and opioids may also take place in vivo, which could cause increased toxicity over and above the involvement of opioid receptors, Information from this study should aid understanding of the mechanism of interactions in human poisoning by agents with membrane stabilizing activity.
The Mechanism of Fluoride-Induced Hypocalcaemia
Authors: Boink A.B.T.J. , Wemer J. , Meulenbelt J. , Vaessen H.A.M.G. , de Wildt D.J.
Published: December 2008

1 Fluoride intoxication leads to sudden cardiac death which has been assumed to result from the accompanying severe hypocalcaemia. The aim of this study has been to investigate the suggestion that fluorapatite formation rather than CaF2 precipitation is responsible for this low calcium.

2 Measurements of free Ca2+ and F- ion concentrations in HEPES buffered solutions containing F-, Ca2+, and phosphate ions at different concentrations in the absence and presence of hydroxyapatite showed that the presence of hydroxyapatite enhanced the decrease of Ca2+ and F- concentration.

3 The ratio of Ca2+:F- clearance was 5:1 which is consistent with formation of fluorapatite. These results support the hypothesis that hydroxyapatite acts as a nucleation catalyst for fluorapatite formation and this process is responsible for the hypocalcaemia induced by fluoride intoxication.

4 The proposed mechanism explains also the metabolic acidosis which is frequently seen in cases of fluoride intoxication.
Phenyl Valerate and Choline Ester Hydrolases in the Platelets of Human, Hen, Rat and Mouse
Authors: Husain Kazim
Published: December 2008

1 The levels of phenyl valerate and choline ester hydrolases in the platelets of human and certain laboratory animals have been determined for comparison.

2 The activities of total phenyl valerate hydrolase (PVase), paraoxon insensitive phenyl valerate hydrolase (PI-PVase), paraoxon and mipafox resistant esterase (PMRE) and propionylcholinesterase (PChE) were maximal in hen followed by mouse, rat and human.

3 Neurotoxicesterase (NTE) and acetylcholinesterase (AChE) activities were concentrated in the platelets of hens followed by humans, rats and mice in order.

4 Maximum concentration of butyrylcholinesterase (BChE) was found in the platelets of hens followed by mice, humans and rats.

5 It is concluded that the normal levels of enzyme activities in the platelets of humans and various species of animals may help to evaluate the exposure risk to neurotoxic organophosphorous compounds.
Phagolysosomal pH in Alveolar Macrophages from Smokers and Nonsmokers
Authors: Nyberg K. , Johansson A. , Camner P. , Johard U. , Eklund A.
Published: December 2008

1 Alveolar macrophages efficiently phagocytize particles deposited in the alveolar part of the lung. Phagolysosomal pH in alveolar macrophages from rabbits, dogs, baboons and guinea pigs is around 5 pH units. A low pH is of importance for clearance of inorganic particles and probably also for defence against bacteria and fungi.

2 Phagolysosomal pH in alveolar macrophages from smokers and non-smokers was measured using fluorescein-conjugated amorphous silica particles as a probe. pH was the same in both groups and similar to earlier studies on alveolar macrophages from animals.

3 The morphological picture between alveolar macrophages from smokers and non-smokers differed clearly with a high number of dense inclusions of great variation in size and shape in macrophages from smokers. Ingested test particles were located in all types of inclusions.

4 We conclude that phagolysosomal pH in human alveolar macrophages is similar to that in several animal species and that it is rather insensitive to influence from the environment.
A Critical Review of the Optimum Duration of Chronic Rodent Testing for the Determination of Non-Tumourigenic Toxic Potential: A Report by the BTS Working Party on Duration of Toxicity Testing
Authors: Betton G. , Cockburn A. , Harpur E. , Hopkins J. , Illing P. , Lumley C. , Connors T.
Published: December 2008

This review indicates that for the detection of non-neoplastic toxic effects:

1 Four decades of accumulated literature provide no lead as to the optimum duration of repeat dose toxicity testing required for all classes of chemicals, although 6 months repeated administration appears adequate for pharmaceuticals.

2 Three month studies predicted the 2 year outcome for 70% of the compounds evaluated in this pilot study using data published by the US National Toxicology Program.

3 In spite of the limitations of this pilot study, this finding is considered encouraging as it is close to that generated previously on more detailed confidential pharmaceutical data.1,2This suggests that the exercise should now be expanded using confidential surveys of industrial data to determine the concordance resulting from the evaluation of a larger group of chemicals.
Organochlorine Pesticide Residues in Human Milk in Kayseri
Authors: Basri üstünbas H. , Adnan Öztürk M. , Hasanoglu E. , Dogan M.
Published: December 2008

In this study: dichlorodiphenyltrichloroethane (DDT) and its metabolites [DDT + dichlorodiphenyl-dichloroethylene (DDE)], BHC (HCH) and their main isomers such as alpha, beta, gamma BHC, aldrin and its metabolite dieldrin, heptachloride, heptachloride epoxide, were investigated in 51 samples of breast milk of 51 lactating women during 1988.

The ages of the mothers, who were working in agriculture, ranged from 17 to 33 y (mean 24.2 y). The concentrations of hexachlorobenzene (HCB), alpha BHC, beta BHC, gamma BHC, heptachloride, aldrin, heptachloride epoxide, pp'DDE, dieldrin, op'DDT, pp'DDT were found as 84± 23, 96± 20, 522± 120, 156± 20, 198± 130, 47± 9, 11 ± 4, 2389± 280, 6.7± 3, 70± 12, 410± 60 ?g kg-1 milk, fat, respectively, measured by gas chromatography (GC) method. The concentrations of chlorinated pesticides in human milk samples from Kayseri were compared with similar data obtained from other countries. The amounts of total BHC and aldrin derivatives were below the acceptable daily intake (ADI), whereas the amount of total DDT derivates was above, of the World Health Organization (WHO).
Clinical and Pathological Findings in Fatal 1,3-Dichioropropene Intoxication
Authors: Hernandez A.F. , Martin-Rubi J.C. , Ballesteros J.L. , Oliver M. , Pla A. , Villanueva E.
Published: December 2008

1 A 27-year-old, previously healthy, worker accidentally drank a solution containing 1,3-dichloropropene.

2 He developed gastrointestinal distress, adult respiratory distress syndrome, haematological and hepatorenal functional impairment and died after 40 h.

3 Damage to the pancreas was also thought to have been caused by the chemical as part of a multiorgan disorder.
Methaemoglobinaemia due to Amyl Nitrite Inhalation: A Case Report
Authors: Machabert Régine , Testud François , Descotes Jacques
Published: December 2008

Methaemoglobinaemia is a potential toxic effect of aliphatic nitrites which are increasingly abused by male homosexuals and drug addicts because of marked vasodilating properties ('poppers'). In most instances, severe complications were described following the ingestion of large quantities of amyl, butyl or isobutyl nitrites. A deficiency in NADHdependent haemoglobin reductase in some patients has been noted. This is the first report of symptomatic methaemoglobinaemia following the inhalation of amyl nitrite.
Study of Lithium Absorption by Users of Spas Treated with Lithium lon
Authors: McCarty J.D. , Carter S.P. , Fletcher M.J. , Reape M.J.
Published: December 2008

This study examines the possible dermal absorption of lithium ion into the blood serum of spa/hot tub bathers.

Fifty-three participants (28 males and 25 females) spent 20 minutes per day, 4 days per week for 2 consecutive weeks in one of two assigned spas. The participants were randomly assigned to one of the two spas after matching based on sex, age, and use of oral contraceptives. The test spa contained 40 ± 5 ppm lithium ion, while the control spa contained no additional lithium ion above the background levels of approximately 0.02 ppm. The exposure in the spa treated with lithium ion (from lithium chloride) simulated the maximum exposure that would be expected in a spa sanitized with lithium hypochlorite. The two spas were maintained at 101 ± 2°F. Serum lithium ion levels before and after spa use were determined using graphite-furnace atomic absorption spectroscopy with a minimum detectable level of lithium ion in serum of 2 ?g l-1 (ppb).

There was no statistically significant difference in serum lithium levels between the control and treatment group at any stage. We conclude that dermal exposure to lithium ion (as would be present after treatment of a spa with lithium hypochlorite) did not result in a detectable increase in the serum lithium ion level.
Effects on Operant Learning and Brain Acetylcholine Esterase Activity in Rats following Chronic Inorganic Arsenic Intake
Authors: Nagaraja T.N. , Desiraju T.
Published: December 2008

1 Very young and adult Wistar rats were given As5+, 5 mg arsenic kg-1body weight day-1(sodium arsenate).

2 Operant learning was tested in a Skinner box at the end of exposure and, in the case of developing animals, also after a recovery period.

3 Acetylcholine esterase (AChE) activity was estimated in discrete brain regions of these animals.

4 The animals exposed to arsenic took longer to acquire the learned behaviour and to extinguish the operant. AChE activity was inhibited in some regions of the brain.
Toxicity of a Novel HMG-CoA Reductase Inhibitor in the Common Marmoset (Callithrix jacchus)
Authors: Owen K. , Pick C.R. , Libretto S.E. , Adams M.J.
Published: December 2008

1 GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1day-1were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7,5 and 20 mg kg-1day-1for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days,

2 Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes, There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1day-1and above.

3 Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment.

4 Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity.

5 Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function.

6 HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.
Interindividual Variation in Biotransformation and Cytotoxicity of Bromobenzene as Determined in Primary Hepatocyte Cultures Derived from Monkey and Human Liver
Authors: Mennes W.C. , van Holsteijn C.W.M. , van Iersel A.A.J. , Yap S.H. , Noordhoek J. , Blaauboer B.J.
Published: December 2008

1 Bromobenzene-evoked hepatotoxicity resulting from cytochrome P450-mediated epoxidation has been studied extensively in rodents in vivo and in rodent hepatocytes. In this paper we present data concerning the formation of bromphenols, glutathione (GSH) depletion and cytotoxicity observed in primate hepatocytes in primary culture after exposure to bromobenzene (BrB).

2 After pre-incubation for 2 or 24 h, hepatocytes were exposed to BrB in concentrations up to 2 mM for 4 or 24 h.

3 In both human and cynomolgus monkey hepatocytes BrB cytotoxicity and GSH depletion were found after exposure to 2 mM BrB. The degree of the observed effects was not influenced by the duration of pre-incubation and/or exposure periods.

4 Major inter-individual differences were observed, which could not be attributed to differences in cytochrome P450-mediated bioactivation rates. This suggests that the variation in individual susceptibility to BrB may be related to interindividual differences in the activity of de-activating (metabolic) pathways.

5 The study of the background of these interindividual differences may contribute to a more complete understanding of the factors ruling sensitivity to BrB or related chemicals.
Expression of Liver Functions in Imrnortalised Rot Hepotocyte Cell Lines
Authors: MacDonald Caroline , Vass Maureen , Willett Brian , Scott Alexander , Grant Helen
Published: December 2008

The differentiated hepatic function of two rat liver cell lines, P9 and SV40RH1, immortalised by transfection with SV40 DNA has been investigated in terms of the glutathione synthesis, and the activities of γ-glutamyltransferase, glutathione-S-transferase and UDP-glucuronosyltransferase. SV40RH1 is a highly differentiated cell line at early passage, but the expression of some aspects of its differentiated phenotype is unstable and some functions are lost by passage 12-13. P9 is a less-well differentiated cell line, with relatively stable expression of functions between passages 4 and 13. In terms of differentiated function both cell lines represent a marked improvement over primary cultures of rat hepatocytes which de-differentiate rapidly within 24-48 h in culture. This retention of liver function in proliferating cell lines offers the opportunity to use such cells in in vitro toxicological studies.
Infiluence of Lindane and Paraquat on Oxidative Stress-Related Parameters of Erythrocytes In Vitro
Authors: Bainy Afonso C.D. , Silva Marcia A.S. , Kogake Mariza , Videlal Luis A. , Junqueira V.B.C.
Published: December 2008

1 The influence of lindane and paraquat on oxidative stress-related parameters of the red blood cell was studied in vitro.

2 Lindane addition did not modify either the t-butyl hydroperoxide-induced oxygen uptake of the erythrocytes and the induction time preceding it, or the activity of catalase, superoxide dismutase, glutathione peroxidase and glucose 6-phosphate dehydrogenase, in conditions of comparable levels of haemoglobin and methaemoglobin.

3 Red blood cells exposed to paraquat exhibited a concentration-dependent decrease in the t-butyl hydroperoxide-induced oxygen consumption and increments in either the induction period or in the activity of catalase and glucose 6-phosphate dehydrogenase, with no changes in superoxide dismutase activity and a small decrement in that of glutathione peroxidase.

4 These data indicate that lindane does not interfere with the oxidant status of the erythrocyte, while paraquat addition leads to an increment in the anti-oxidant capacity of the red blood cell.
No Beneficial Effect of N-acetylcysteine Treatment on Broncho-alveolar Lavage Fluid Variables in Acute Nitrogen Dioxide Intoxicated Rats
Authors: Meulenbelt J. , van Bree L. , Dormans J.A.M.A. , Sangster B.
Published: December 2008

1 In previous studies a rat inhalation model was developed to investigate the efficacy of treatment in acute NO2 intoxication.

2 N-acetylcysteine (NAC) was administered intravenously to study its effect on biochemical variables in broncho-alveolar lavage fluid in acute NO2 intoxicated rats. It was decided to start the intravenous administration of NAC 24 h before the exposure to NO2 to induce higher intracellular glutathione (GSH) levels in lung cells of NAC-treated rats compared to not NAC-treated rats. Because, on theoretical grounds, the therapeutic effect of NAC may be expected to be especially marked during the first 24 h after exposure, the rats were observed for a period of 24 h and were then killed for investigation. A loading dose of 85 mg kg-1 h-1 or 170 mg kg -1 h-1 was followed by a continuous infusion (until autopsy) with a dose of 225 mg kg-1 24 h-1 or 450 mg kg -1 24 h-1 respectively.

3 Twenty four hours after exposure to 175 ppm NO2 (1 ppm is 1.88 mg m-3) for 10 min, NAC did not reduce the increase of variables in bronchoalveolar lavage fluid which reflect the severity of lung damage.

4 The protein and albumin concentration and the activities of angiotensin converting enzyme and alkaline phosphatase in broncho-alveolar lavage fluid after NO 2 exposure were even more increased in the NAC-treated than in the saline-treated rats, but none of the differences was statistically significant.

5 In sham exposed rats no effect of NAC was observed.
Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure
Authors: Groth G. , Freundt K.J.
Published: December 2008

1 A continuous 5 h-exposure to approximately 440 ppm tert-butyl acetate in air (via a tracheal canule) resulted in continuously increasing concentrations of tert-butyl acetate and tert-butyl alcohol (metabolite of tert-butyl acetate) in the blood of rats.

2 This accumulation of tert-butyl acetate and tert-butyl alcohol was reproduced during a continuous exposure to about 900 ppm tert-butyl acetate in air over a period of 4 h and 15 min. After the inhalation approximately 50% of the blood level of tert-butyl acetate decreased within 45 min, but that of tert-butyl alcohol remained unchanged at a high level.

3 The accumulation of tert-butyl acetate and tert-butyl alcohol should be relevant for the health risk assessment at the workside.
Amalgam Tooth Fillings and Man's Mercury Burden
Authors: Halbach Stefan
Published: December 2008

Next to nutrition, amalgam fillings represent the main source for exposure of the general population to mercury. Toxicological considerations focus on the dose of mercury resulting from such exposure. Various approaches to estimate this dose are reviewed. Introducing the dose into the known toxicokinetic model for mercury, tissue and blood and urine concentrations related to mercury release from the fillings can be predicted. These agree well with autopsy and in vivo observations. An assessment of the health hazard for individuals with amalgam fillings shows that the combined mercury intake from food and amalgam does not exceed the acceptable daily intake. In addition, blood and urine mercury concentrations of amalgam bearers are below one tenth of the critical values associated with the onset of early symptoms or of subclinical effects attributable to mercury.