scispace - formally typeset
Search or ask a question

Showing papers in "Journal of Applied Toxicology in 1982"


Journal ArticleDOI
TL;DR: It appears that smokers have less sensitivity to nasal irritants, the first instance of a substantial chemosensory difference between smokers and non‐smokers.
Abstract: Carbon dioxide inhaled through the nose in concentrations above 10% evokes nasal irritation. As concentration is increased, a non-systemic, reflexive interruption of inhalation eventually occurs in most persons. This study revealed that smokers have a considerably higher threshold for the reflex. The elevation of threshold occurred to a comparable degree in both male and female smokers, although females generally had a lower threshold than males. It therefore appears that smokers have less sensitivity to nasal irritants. This marks the first instance of a substantial chemosensory difference between smokers and nonsmokers.

53 citations


Journal ArticleDOI
Henry E. Holden1
TL;DR: It is suggested that a negative somatic‐cell response can be taken as highly predictive of negative results in a germ cell assessment and an inherent relative insensitivity of germ cells themselves to mutagenic chemicals is suggested.
Abstract: A variety of in vivo mammalian test models are available for screening of chemicals for mutagenicity at the chromosomal level. These models have been grouped into those focusing on somatic cell effects and those dealing with germ cell effects. An analysis of available literature indicates that 76 compounds have been tested from chromosome effects in both somatic and germ cells. Of these, concordant results (positive-positive or negative-negative) were obtained with 58 compounds. Of the remaining 18 compounds with discordant results, all were positive in somatic cells, but negative in germ cell assays. These results suggest an inherent relative insensitivity of germ cells themselves to mutagenic chemicals. In the context of screening for safety evaluation purposes, this analysis suggests that a negative somatic-cell response can be taken as highly predictive of negative results in a germ cell assessment.

49 citations


Journal ArticleDOI
TL;DR: Analysis of the forms of arsenic in portal blood after administration of arsenite via the small intestine revealed a rapid reduction of arsenate to arsenite, followed by linear rates of production of methylarsonic acid and dimethylarsinic acid.
Abstract: After a single oral dose of sodium [74As] arsenate to male Wistar rats, arsenic was rapidly absorbed and accumulated in the blood and to a lesser extent in the liver, kidneys, lungs and spleen. Within 1 h of dosing, arsenic was present in the blood, liver and spleen predominantly in the methylated forms (methylarsonic acid and dimethylarsinic acid), whereas in the lung and kidneys, approximately 50% was in the inorganic form. Intravenous injection of sodium [74As] arsenate resulted in a pattern of arsenic species in the blood and kidneys similar to that seen after oral administration, suggesting that the gut flora does not contribute significantly to biotransformation of arsenic in vivo. Analysis of the forms of arsenic in portal blood after administration of arsenate via the small intestine revealed a rapid reduction of arsenate to arsenite, followed by linear rates of production of methylarsonic acid and dimethylarsinic acid.

43 citations


Journal ArticleDOI
TL;DR: The obtained results indicate that cadmium‐induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.
Abstract: Cadmium chloride was administered by gavage to pregnant rats from day 7 to day 16 of gestation. Cadmium, when administered at a dose of 40 mg Cd per kg per day, was associated with significant maternal toxicity, placental injury and an increased fetal burden of cadmium. At lower dose levels (2–20 mg Cd per kg per day), fetal development was retarded. Teratogenic effects were not observed and the fetal cadmium concentrations did not differ significantly from the controls, despite the marked cadmium accumulation in the placenta and maternal tissues. The body-weight gain during gestation of all cadmium-treated females was reduced and an absolute weight of adrenals in females given cadmium at doses 4 mg kg−1 and higher was significantly increased. The obtained results indicate that cadmium-induced fetal toxicity is associated with concomitant maternal toxicity and alteration in placental function.

39 citations


Journal ArticleDOI
TL;DR: A comparison of autopsy results from both groups indicated that resorptions were increased when compared with rats that did not receive caffeine; this effect was more marked in the gavage group than in the ad libitum sipping group.
Abstract: Pregnant FDA-strain Osborne-Mendel rats were administered repeated doses of caffeine by oral intubation (gavage) and by administration in the drinking water (ad libitum sipping). When [1-methyl-14C]caffeine was administered at a dosage of 80 mg per kg per day by ad libitum sipping on days 12 to 15 of gestation, the amounts of radioactivity in blood were variable; the highest level on day 12 was 0.2% of the dose per ml of blood. The highest blood level of caffeine observed during a 24-h sampling period averaged 5.7 micrograms ml-1. When [14C]caffeine was administered by gavage at a dosage of 80 mg kg-1 on day 12, the blood level of radioactivity reached a peak of 0.4% of the dose per ml of blood and declined rapidly thereafter. The highest amount of caffeine observed in blood averaged 63.1 micrograms ml-1, 1 h after gavage. The overall blood elimination half-life of radioactivity in pregnant rats treated by gavage was 2.6 h, and the half-life of caffeine in blood was 1.7 h. The levels of radioactivity in the fetus and maternal muscle per unit weight were comparable after each method of administration. A comparison of autopsy results from both groups indicated that resorptions were increased when compared with rats that did not receive caffeine; this effect was more marked in the gavage group than in the ad libitum sipping group. Ectrodactyly was observed only in offspring of the gavage group. The incidences of ectrodactyly or resorptions did not appear to be directly related to nutrition or fluid intake.

38 citations


Journal ArticleDOI
TL;DR: In this article, the use of oysters and mussels as indicators of heavy metal contamination in the Derwent River and adjacent coastal waters has been investigated using field accumulation and depuration experiments, variation of metal content with size and prediction of water movements.
Abstract: The contamination of an estuary with heavy metals by a single large ore processing plant provided a unique opportunity to assess the use of mussels and oysters as indicators of heavy metal contamination. Field accumulation and depuration experiments, variation of metal content with size and prediction of water movements are described from shellfish surveys covering the Derwent River and adjacent coastal waters. Oysters were found to be suitable for monitoring zinc, cadmium, lead and copper contamination. Mussels were also suitable for monitoring zinc, cadmium and lead, but in this instance were found unsuitable for monitoring copper as the surveys indicate that copper accumulation is suppressed in mussels in a contaminated environment. The rate of accumulation and depuration of metals by oysters and mussels in field trials has been related to the anatomy of the animals and the sequestering of some metals in granulocytes. Uneven metal distribution between gonad and other tissues has been found to cause seasonal variation of heavy metals in oysters.

37 citations


Journal ArticleDOI
TL;DR: The effects of lifetime dietary administration of zearalenone, a fungal estrogen produced by Fusarium spp.
Abstract: The effects of lifetime dietary administration of zearalenone, a fungal estrogen produced by Fusarium spp., were studied in FDRL Wistar rats. Animals were fed a control diet or a diet supplemented with zearalenone at levels of 0.1, 1.0 or 3.0 mg per kg body weight per day. The animals used were derived from F0 parents fed equivalent levels of zearalenone for 5 weeks before mating, and throughout mating and gestation, but not during lactation. Feeding of zearalenone at 1.0 and 3.0 mg kg−1 to male rats caused a significant decrease in body weight gain compared with controls. During the study, sporadic depressions in body weights occurred in females fed 1.0 and 3.0 mg per kg. However, no differences were noted at the end of the study. No significant differences among groups were found in the hematology, clinical chemistry or urine analysis data measured during or at the termination of the study. At the end of the study, significantly increased liver weights at the 3.0 mg kg−1 dose level and uterine weights at 1.0 and 3.0 mg kg−1 were noted in female rats. These weight differences did not correlate with any clinical or morphological finding. In rats receiving the high dose level of zearalenone, a greater incidence of increased medullary trabeculation of the femur was noted. The degree of medullary trabeculation was scored on a scale from 0 to 4; statistically significant increased scores were found in male and female rats at the high dose level compared to control rats. Other microscopic findings were unremarkable; no tumorigenic effect of zearalenone was noted.

34 citations


Journal ArticleDOI
TL;DR: In the results reported here, MS/MS (tandem mass spectrometry) was found to detect nitroaromatic compounds in fractionated and unfractionated diesel soot extracts, and ranged from two‐ to four‐ring polynuclear aromatic hydrocarbon derivatives and were primarily mono‐nitroderivatives.
Abstract: Correlations between direct-acting mutagens in diesel emissions and the activity of nitroaromatic compounds have been noted, but detection and identification of nitro-compounds in diesel particulates has remained an elusive problem. In the results reported here, MS/MS (tandem mass spectrometry) was found to detect nitroaromatic compounds in fractionated and unfractionated diesel soot extracts. The nitro-compounds detected ranged from two- to four-ring polynuclear aromatic hydrocarbon derivatives and were primarily mono-nitro derivatives. An aromatic fraction from diesel fuel reacted with NO2 resembled diesel exhaust extracts from an engine operating on the same fuel. Therefore, it is possible that nitroaromatic derivatives in diesel exhaust may be in part due to unburned fuel residues reacting with NO chi formed in the combustion process. The utility of MS/MS in comparing complex mixtures from different sources or subfractions thereof is discussed.

34 citations


Journal ArticleDOI
TL;DR: Feeding of zearalenone caused decreases in fertility, number of viable offspring per litter and numbers of corpora lutea, implantations and resorptions per dam, and a dose‐related increase in absolute and relative thyroid, pituitary and adrenal gland weights occurred in male and female rats of both the F1 and F1A generation.
Abstract: The toxicity of zearalenone was studied in two generations of Wistar rats over approximately 10 months. Zearalenone was administered in the diet; the dose levels used were 0, 0.1, 1.0 and 10.0 mg per kg body weight per day in all generations. Animals in the F0 generation were bred twice to produce F1A and F1B generations. The F1A generation was bred to produce the F2A generation. The only lesion found at necropsy that could be attributed to zearalenone administration was increased medullary trabeculation of the femur in animals given the high dose. A dose-related increase in absolute and relative thyroid, pituitary and adrenal gland weights occurred in male and female rats of both the F1 and F1A generation. The alteration in the weights of these endocrine organs is probably a result of the estrogenic activity of zearalenone. Feeding of zearalenone caused decreases in fertility, number of viable offspring per litter and numbers of corpora lutea, implantations and resorptions per dam. Statistically significant differences were noted in the incidences of a number of skeletal and soft tissue abnormalities in both the F1B and F2A1 fetuses, especially at doses of 1.0 and 10.0 mg kg-1. These lesions most likely indicate a delay in fetal development. Unequivocal teratogenic effects could not be defined.

30 citations


Journal ArticleDOI
TL;DR: It is demonstrated that dietary T‐2 toxin at levels up to 20 ppm cause similar effects attributable to food refusal and alimentary irritation in both species, however, mice and rats were relatively resistant to hematopoietic suppression.
Abstract: The subacute toxic effects of dietary T-2 toxin were compared in young male Wistar rats, young male Swiss mice and juvenile Swiss mice. Purified T-2 toxin was fed in the diet at levels of 10 or 20 ppm for 2 or 4 weeks. Dose-related depressions in food consumption and weight gain consistently occurred in all animals fed T-2 toxin. Hyperkeratosis of the squamous gastric mucosa, atrophy of the thymus and thymus-dependent lymphoid tissues, and lymphopenia occurred in all animals exposed to T-2 toxin. These effects were most severe in juvenile mice, and least severe in rats. In addition, juvenile mice fed the 20-ppm level developed erythroid hypoplasia and became severely anemic by 4 weeks. These results demonstrate that dietary T-2 toxin at levels up to 20 ppm cause similar effects attributable to food refusal and alimentary irritation in both species. However, mice and rats were relatively resistant to hematopoietic suppression. Only the juvenile mice fed 20 ppm developed this potentially lethal toxic effect.

29 citations


Journal ArticleDOI
TL;DR: The results of this investigation show that, as already observed in experimental animals, commercial mixtures of PCBs have a porphyrinogenic activity in man, as well.
Abstract: Urinary porphyrin excretion was investigated in 67 workers occupationally exposed to commercial mixtures of polychlorinated biphenyls (PCBs) by determining the concentration of uro-, hepta-, hexa-, penta-, and coproporphyrin homologues. The workers had a mean blood PCB concentration of 386 ± 257 ppb (mean ± SD; range 162–1319 ppb). These values are at least ten-fold higher than that expected in a population not occupationally exposed to PCBs. No qualitative alterations of the urinary porphyrin excretion were found and the uroporphyrin: coproporphyrin ratio remained normal. There was a definite increase in the excretion of all the porphyrinic homologues, so that the average concentration of total porphyrins in urine was 94.5 μg 1−1 in the exposed group versus 48.3 μg 1−1 in the control group. This excretory pattern of porphyrins corresponds to that usually observed in the first stage of chemical porphyria induced by polyhalogenated aromatic hydrocarbons. In accordance with current knowledge, this should be interpreted as a consequence of the specific inductive properties of PCBs on liver microsomal enzymes. The results of this investigation show that, as already observed in experimental animals, commercial mixtures of PCBs have a porphyrinogenic activity in man, as well.

Journal ArticleDOI
TL;DR: The data indicate that the absorption of fluoride through this keratinized epithelium occurs mainly by the diffusion of non‐ionic HF.
Abstract: The fractional absorptions of fluoride, 3H2O, 125I and 14C-DMO from the hamster cheek pouch were determined as functions of solution pH. When the pH was less than 5, fluoride absorption rate was inversely related to pH. The absorption rates of the other substances were not influenced by pH. The fractional absorptions of fluoride and 3H2O were independent of fluoride concentrations over the range 1-53 mM. The data indicate that the absorption of fluoride through this keratinized epithelium occurs mainly by the diffusion of non-ionic HF.

Journal ArticleDOI
TL;DR: Pregnant rats in the high‐exposure group gained less weight than controls during gestation and the reduced weight gain was accounted for by the reduced size of the fetuses and placentas, even though maternal body weight was unaffected by the exposure.
Abstract: On days 12-16 of gestation pregnant rats were exposed to heavy distillate (HD), the highest-boiling material derived from the solvent refined coal-II (SRC-II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg 1-1 [1.8 microgram, mass medium aerodynamic diameter (MMAD)]; groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg 1-1) were largely unaffected. Embryo lethality during mid- and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high-exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.

Journal ArticleDOI
TL;DR: The content, chemical form and distribution of mercury and selenium were determined for several samples of canned tuna, and there was no apparent correlation between the total levels of both elements.
Abstract: The content, chemical form and distribution of mercury and selenium were determined for several samples of canned tuna Samples represented albacore, bluefin, skipjack and yellowfin species, and were packed in either water or vegetable oil Recently-processed samples (less than one year old) and much older samples (8-29 years old) were examined Methylmercury was the predominant mercury form in all samples, comprising 574-947% of the total mercury content For these samples, 76-448% of the total selenium content was present as selenate There was no apparent effect of packing medium, species or sample age on the methylmercury and selenate percentages Although the total selenium content exceeded that of total mercury, there was no apparent correlation between the total levels of both elements Sample age influenced the level of water-extractable mercury and selenium in canned tuna For recently canned samples, an average of 270% of the total mercury and 556% of the total selenium content were water-extractable However, for the older samples, the corresponding respective average extractable levels were 464 and 482% For both categories, inorganic mercury and selenate were more extractable, on an average percentage basis In addition, an average of 72% of the total mercury content was benzene-extractable

Journal ArticleDOI
TL;DR: Adult male rats receiving styrene by gavage for 100 days exhibited a significant dose‐dependent increase in hepatic benzo[a]pyrene hydroxylase and ammopyrine‐N‐demethylase, a decrease in glutathione‐S‐transferase and no change in glucose‐6‐phosphatase.
Abstract: Adult male rats receiving styrene by gavage (200 or 400 mg kg-1, 6 days a week) for 100 days exhibited a significant dose-dependent increase in hepatic benzo[a]pyrene hydroxylase and aminopyrine-N-demethylase, a decrease in glutathione-S-transferase and no change in glucose-6-phosphatase. A decrease in the activity of mitochondrial succinic dehydrogenase and beta-glucuronidase was also observed. Activity of acid phosphatase was decreased only at the higher dose level. Levels of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated only at the higher dose level. The absolute and relative weights of the liver of control and treated animals showed no significant difference. Histopathological studies of the liver tissue revealed tiny areas of focal necrosis, consisting of few degenerated hepatocytes and inflammatory cells at the higher dose level only.

Journal ArticleDOI
TL;DR: Cadmium plays no useful role in the organism and its intake should be limited as much as possible, although being ubiquitous it cannot be completely eliminated.
Abstract: The health hazards of cadmium have attracted increased attention since the rock-soil-plant-animal-man relationship became better known, and when it was realized that low doses are cumulative over a very long time and that increasing industrial pollution may endanger the general population. Major sources are mining and smelting, metal coating, welding, incineration of refuse, fossil fuels and use of sewage sludge as fertilizer. Intoxication usually results from ingestion or inhalation, but the pathogenesis is not well understood. With chronic intoxication, the critical organ is the kidney, where one third of the body cadmium may accumulate. Apart from diseases so far recognized in man, a large number of pathological conditions have been produced in experimental animals, including congenital abnormalities, ovarian, testicular and brain lesions, as well as interference with the immune system. Their full significance for man is not yet known. Cadmium plays no useful role in the organism and its intake should be limited as much as possible, although being ubiquitous it cannot be completely eliminated. Legislation for maximum permissible levels in different food items was attempted, but is not workable and is not in the best interest of the consumer. Instead, the whole food basket of the consumer should be monitored to limit weekly intake to prescribed levels. In addition, hygienic measures should be encouraged, including cleaning, peeling or blanching of fruit and vegetables, removal of outer leaves of cabbage and lettuce to eliminate the effects of aerial pollution, discretion in using sewage sludge as fertilizer, washing hands and possibly avoiding excessive consumption of kidneys and livers.

Journal ArticleDOI
TL;DR: The percentage of total defects was increased significantly over control in the 100 mg l−1 HOCl group; however, monochloramine did not produce any significant changes in rat fetuses at any dose level.
Abstract: Chlorine dioxide (ClO2) or monochloramine (NH2Cl) may be considered as an alternative to chlorine (HOCl) as a disinfectant in public water supplies, since chlorination produces trihalomethanes. This study was conducted to determine the effect of chlorine and monochloramine on rat fetuses. Female rats were administered 0, 1, 10 or 100 mg l−1 NH2Cl or HOCl daily in the drinking water for 2 1/2 months prior to and throughout gestation. Rats were sacrificed on Day 20 of gestation and fetuses were preserved for soft-tissue and skeletal examination. No significant increase in fetal resorptions was found in any treated group. A slight increase in skeletal variants (such as incompletely ossified or missing sternebrae, or rudimentary ribs) was seen in 10 and 100 mg l−1 HOCl groups. Soft-tissue defects, mainly improper orientation of the heart or adrenal agenesis, were observed in the 100 mg l−1 HOCl group. The percentage of total defects (skeletal and soft-tissue) was increased significantly over control in the 100 mg l−1 HOCl group; however, monochloramine did not produce any significant changes in rat fetuses at any dose level.

Journal ArticleDOI
TL;DR: Studies on the binding spectra of certain alkaloids with rat liver microsomes revealed that brucine, scopolamine and strychnine are type I compounds, whereas boldine, emetine, nicotine, reserpine and sanguinarine show type II binding, while colchicine and solanine failed to produce any measurable binding spectRA.
Abstract: Studies on the binding spectra of certain alkaloids with rat liver microsomes revealed that brucine, scopolamine and strychnine are type I compounds, whereas boldine, emetine, nicotine, reserpine and sanguinarine show type II binding. In contrast, colchicine and solanine failed to produce any measurable binding spectra. In vitro incubation of colchicine, nicotine or scopolamine with microsomal suspensions and NADPH resulted in demethylation of these alkaloids, while the incubation of boldine, brucine, emetine, reserpine, sanguinarine or solanine showed little or no dealkylation reaction. Furthermore, the effect of these alkaloids on the in vitro microsomal metabolism of a drug, benzphetamine, has also been studied.

Journal ArticleDOI
TL;DR: The dose–response relationship between the number of cigarettes smoked versus urine mutagenic activity and the persistence of mutagens in the urine after the cessation of smoking have been examined.
Abstract: Cigarette smoke is a complex chemical mixture which displays a number of biological activities including mutagenesis. The absorption of smoke components by the lungs results in their systemic distribution, which then leads to the presence of mutagens in the urine. The detection of mutagenic substances in the urine by short-term bioassays has been suggested for use in monitoring human exposure to various carcinogenic/mutagenic substances. In this connection, we felt that further studies on the mutagenic activity present in cigarette smokers' urine were needed. In the present studies, the dose-response relationship between the number of cigarettes smoked versus urine mutagenic activity and the persistence of mutagens in the urine after the cessation of smoking have been examined. The studies were carried out on a group of smokers and non-smokers in Lexington, Kentucky. Although a dose-response relationship (urine mutagenicity versus the number of cigarettes smoked per day) was not observed in the group of smokers assayed, a linear dose-response relationship was detected in an individual smoker who smoked a varying number of cigarettes over eight successive days. In another smoker who ceased smoking, mutagens were detected in the urine for one week. The urine mutagenicity data from a group of smokers and non-smokers should prove useful in extending this technique to the monitoring of other environmental exposure.

Journal ArticleDOI
TL;DR: It is concluded that lantana poisoning can be treated by removing the residual toxin from the rumen and re‐establishing rumen fermentation.
Abstract: Lantana poisoning was induced in sheep by giving 4 g kg−1 Lantana camara orally. When the contents of the rumen were removed from sheep three or six days after giving them lantana and placed into the empty rumens of normal sheep, the recipient sheep became intoxicated. Administration of purgatives such as raw linseed oil or Glauber's salts orally, or administration of bethanechol subcutaneously failed to stimulate rumen motility in lantana poisoned sheep and are therefore unlikely to be effective in eliminating residual toxin from the rumen. Intravenous administration of a multiple electrolyte solution to lantana poisoned sheep improved rumen motility, and motility was increased even more when 2–3 1 of freshly collected rumen liquid was given orally to rehydrated animals. However, these treatments did not restore motility to normal and animals treated by these methods did not survive the intoxications. The effect of manually removing the rumen contents from sheep with lantana poisoning was studied in sheep with chronically‐implanted rumen cannulae. When the rumen contents were removed from sheep three days after lantana was given and replaced with fresh rumen contents or a multiple electrolyte solution, there was a significant increase in survival compared with untreated sheep. Removal of rumen contents at six days and replacement with fresh rumen contents or simulated rumen contents containing a buffered mixture (pH 6.7, ‐ 330 mV) of lucerne and rumen liquid, also significantly increased survival, but replacement with a multiple electrolyte solution did not. It is concluded that lantana poisoning can be treated by removing the residual toxin from the rumen and re‐establishing rumen fermentation. Copyright

Journal ArticleDOI
TL;DR: It is suggested that HCBD or a metabolite causes disruption of mitochondria and this results in an influx of water into the cells, and normal concentrations of Na+ and K+ are maintained by an intact Na+ pump.
Abstract: The effect of a single i.p. dose of 200 or 300 mg kg-1 hexachloro-1:3-butadiene (HCBD) on liver morphology, water, sodium and potassium ion content, cation movement and non-protein sulphydryl (NP-SH) content has been studied in rats. There was a rapid, dose-related increase in liver water which reached a maximum between 16 and 24 h after HCBD administration and then returned to control values by day 4. Associated with the increased water, there was an increase in the Na+ and K+ ions when related to the dry weight of the liver. However, the actual concentration of both cations in total liver water did not alter. The total liver DNA, protein or cytochrome P-450 concentration did not change, at a time when there was a maximal increase in liver water. There was a rapid decrease in liver NP-SH, which reached a nadir (50% of control) 8 h after HCBD administration, then increased to 150% of normal on day 5 and returned to normal by day 10. On histopathological examination, the liver appeared essentially normal, apart from a slight fatty change. Ultrastructural changes were, however, observed 8 h after dosing, when periportal hepatocytes contained occasional swollen mitochondria, whereas centrilobular hepatocytes appeared normal. By 16-24 h, mitochondrial swelling was marked in most periportal hepatocytes and some alteration in smooth endoplasmic reticulum was seen. It is suggested that HCBD or a metabolite causes disruption of mitochondria and this results in an influx of water into the cells. Normal concentrations of Na+ and K+ are, however, maintained by an intact Na+ pump.

Journal ArticleDOI
J. G. Miller1
TL;DR: In this article, a substantial body of diverse and largely uncoordinated information on the effects of petroleum discharges in marine environments is available in the scientific literature and the application of an ecotoxicological approach, however, allows the development of critical evaluation models and frameworks which attempt to integrate and apply general principles of toxicology and ecology to a synthesis of the available information on effects induced by petroleum hydrocarbons in the marine environment.
Abstract: The utilization of petroleum resources as an energy source for society results in the global discharge of significant quantities of petroleum hydrocarbons into the marine environment (about 6 × 106 tonnes per year). Consequently, there is a need to evaluate the ecological impacts of petroleum in the marine environment and to identify the scope and dimensions of resultant impacts. Currently, a substantial body of diverse and largely unco-ordinated information on the effects of petroleum discharges in marine environments is available in the scientific literature. The application of an ecotoxicological approach, however, allows the development of critical evaluation models and frameworks which attempt to integrate and apply general principles of toxicology and ecology to a synthesis of the available information on effects induced by petroleum hydrocarbons in the marine environment. These aspects are discussed in relation to the significance of sub-lethal and lethal concentrations of petroleum hydrocarbons (e.g. aromatic fractions) within marine ecosystems.

Journal ArticleDOI
M. Emura1, H.-B. Richter-Reichhelm1, P. Schneider1, C. Schoch1, Ulrich Mohr1 
TL;DR: In this article, the toxic and transforming effects of ten environment-related polycyclic aromatic hydrocarbons (PAH's) using early passage mixed cultures of fetal Syrian golden hamster lung cells were evaluated by applying a linear regression to the relative number of surviving colonies.
Abstract: Standardized procedures were developed to compare quantitatively the toxic and transforming effects of ten environment-related polycyclic aromatic hydrocarbons (PAH's) using early passage mixed cultures of fetal Syrian golden hamster lung cells. Evaluation of toxicity was attempted by applying a linear regression to the relative number of surviving colonies. Transformation data were fitted satisfactorily to the one-hit model. Used as a monitor compound in each subexperiment, benzo[a]pyrene (BaP) showed dose-related colony reduction (0.01–0.5 μg ml−1). Benzo[b]fluoranthene (BbF), indeno[1,2,3-cd]pyrene (IcdP), benzo[k]fluoranthene (BkF) and benzo[e]pyrene (BeP) were generally colony enhancing at dose ranges up to 1.0 μg ml−1. Fluoranthene (FLT), pyrene (PYR), chrysene (CHR), benzo[ghi]perylene (BghiPL) and benz[a]anthracene (BaA) were neither stimulatory nor inhibitory to colony formation. For transformation induction, BaP was over 14-fold more effective than BbF, IcdP or BaA. The other PAH's showed no transformation.

Journal ArticleDOI
TL;DR: It is suggested that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.
Abstract: Comparative effects of aldrin, dieldrin, endrin, isodrin and telodrin, on different ATPase activities in beef heart mitochondrial and rat brain synaptosomal fractions were determined in vitro. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method and the rat brain synaptosomes were prepared by Ficoll-sucrose gradient centrifugation method. Na+-K+-ATPase, oligomycin-sensitive and -insensitive Mg2+-ATPases, and K+-paranitrophenylphosphatase were determined in rat brain synaptosomes. In beef heart mitochondria, only the Mg2+-ATPase activities were determined. Concentration response curves were determined by assaying the enzyme activities in the absence and presence of 10-120 microM concentrations of each test chemical. Beef heart mitochondrial (oligomycin-sensitive) Mg2+-ATPase activity was inhibited by all five chemicals at all the concentrations tested. Aldrin and telodrin were the most potent inhibitors with an IC50 of 40 and 80 microM, respectively. About 30% was observed with dieldrin, endrin and isodrin, and the inhibition was not concentration-dependent. Oligomycin-insensitive Mg2+-ATPase was not significantly inhibited by any chemical except aldrin. Rat brain synaptosomal ATPases were also sensitive to these compounds. Aldrin and telodrin were more effective than other compounds. A 50% inhibition of oligomycin-sensitive Mg2+-ATPase activity was obtained at 80 microM of aldrin and telodrin. Na+-K+-ATPase and oligomycin-insensitive Mg2+-ATPase activities showed a maximum inhibition of 40% at the highest concentration tested for aldrin and telodrin. K+-paranitrophenylphosphatase was not inhibited significantly by any compound tested. These results suggest that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.

Journal ArticleDOI
R.M. Stern1, E. Thomsen, M. Anderson, Pauli Kiel, Henry Larsen 
TL;DR: The origin of mutagenicity in S. typhimurium in response to exposure to welding fumes, a complex mixture of metallic oxides and other inorganic compounds, was studied through the quantitative use of the histidine revertant Salmonella microsome test of Ames as mentioned in this paper.
Abstract: The origin of mutagenicity in S. typhimurium in response to exposure to welding fumes, a complex mixture of metallic oxides and other inorganic compounds, was studied through the quantitative use of the histidine revertant Salmonella microsome test of Ames. Dose-response experiments and factorial design studies independently showed the mutagenic activity to be due to the presence of soluble Cr(VI). A rate of 65 ± 15 revertants per plate per μg Cr(VI) was found for all fumes produced by the metal inert gas welding of stainless steel. A significantly reduced rate was found for manual metal arc welding fumes. The presence of other metals in low oxidation states (e.g. Fe(0), Fe(II), Al(0)), results in a significant reduction of the Cr(VI), accompanied by a corresponding decrease of the absolute revertant rate per unit fume mass.

Journal ArticleDOI
TL;DR: Both ethanol and acetaldehyde were toxic to the mouse embryos at this stage of their development, and reasonably close correlation was found between morphological abnormalities and reduction in DNA synthesis.
Abstract: C3H mouse embryos were supported in an in vitro culture system over 28-h periods between 8 and 10 days post-conception. Morphological development over this critical period of organogenesis was monitored in the following respects: somite count; presence or absence of heart beat; central nervous system size and symmetry; neural tube fusion. Total embryo DNA synthesis, determined by 3H-thymidine uptake of the embryo over the last 4 h of the culture period, was compared with morphological findings. The effects of varying concentrations of ethanol and acetaldehyde, respectively, on morphology and DNA synthesis were determined at the dose levels tested. Both ethanol and acetaldehyde were toxic to the mouse embryos at this stage of their development, and reasonably close correlation was found between morphological abnormalities and reduction in DNA synthesis.

Journal ArticleDOI
TL;DR: In this paper, the authors conducted a study to determine the quantity and quality of trihalomethanes in the soft drinks and found that the trihomethane concentration was highest in the Colas and lowest in Sprite and 7 Up.
Abstract: When chlorine is employed as a surface disinfectant, the chlorinated organic compounds ‘trihalomethanes’ are formed from the interaction of chlorine with various organic substances in the water. Epidemiological studies have demonstrated the association between increased cancer mortality and high concentrations of trihalomethanes. The soft drink industry has been using granular activated carbon (GAC) to eliminate chlorine and trihalomethanes in water processing for many years. Studies were conducted to determine the quantity and quality of trihalomethanes in the soft drinks. The total trihalomethanes concentration was highest in the Colas and lowest in Sprite and 7 Up. It is hypothesized that this variation is due to the method of Coca extraction and the presence of caramel.

Journal ArticleDOI
TL;DR: Skin on the forearms of male human volunteers exposed to aqueous HgCl2 solutions was exposed to ensure that loss of mercury from the test solution was equivalent to percutaneous absorption to indicate that the absorption rate is a directlyrelated function of concentration and an indirectly related function of time of exposure.
Abstract: Skin on the forearms of male human volunteers was exposed to aqueous HgCl2 solutions. It was assumed that loss of mercury from the test solution was equivalent to percutaneous absorption. Two parameters important for influencing uptake considered as the rate of absorption were investigated: the concentration of HgCl2 solutions (0.01, 0.1 and 0.2 M) and the time of exposure (5, 10, 15, 30 and 60 min). The absorption rate from 0.1 M HgCl2 solution decreased from 9.3 micrograms cm-2 min-1 during a 5 min exposure to 2.5 micrograms cm-2 min-1 during a 1 h exposure. A ten-fold decrease of HgCl2 concentration resulted in an approximately ten-fold decrease of the absorption rate, from 4.6 to 0.4 microgram cm-2 min-1 during a 30 min exposure. The results indicate that the absorption rate is a directly related function of concentration and an indirectly related function of time of exposure.

Journal ArticleDOI
TL;DR: In this article, a method for the measurement of total platinum in plasma and urine, using flameless atomic absorption spectrophotometry, which is sensitive and reproducible enough to permit pharmacokinetic studies on cis-dichlorodiammineplatinum(II), was described.
Abstract: A method is described for the measurement of total platinum in plasma and urine, using flameless atomic absorption spectrophotometry, which is sensitive and reproducible enough to permit pharmacokinetic studies on cis-dichlorodiammineplatinum(II). The plasma platinum concentrations are determined after ten-fold dilution in 0.5% nitric acid, and urine is analysed after twenty-fold dilution in distilled water. The use of tantalized-treated graphite furnaces prior to each dosing series allows one to increase the sensitivity and reproducibility of measurements. A comparative study made on the classic method, which consists of introducing samples manually, and an original automatic one, confirms the latter's superiority. By taking ten measurements, the reproducibility of the injections is 1.89% for calibration points containing 100 ng ml−1 of platinum and is 2.47% for those containing 35 ng ml−1 of platinum. The reproducibility of the method was determined on plasma samples to which cis-DPP had been added, using an automatic sample injection system. It varies between 4.73% and 2.93% for platinum concentrations between 0.32 μg ml−1 and 2.61 μg ml−1. This represents the range of the concentrations observed in the kinetic studies. The absolute detection limit of platinum is 10 ng ml−1.

Journal ArticleDOI
TL;DR: Some of the more interesting and significant recent Australian studies of plant toxins are those dealing with furanosesquiterpenoid essential oils, irritant diterpene esters, thiaminase I, trihydroxyindolizidine, carboxyatractyloside and oxalates.
Abstract: Some of the more interesting and significant recent Australian studies of plant toxins are those dealing with furanosesquiterpenoid essential oils, irritant diterpene esters, thiaminase I, trihydroxyindolizidine, carboxyatractyloside and oxalates Furanosesquiterpenes, found mainly in Myoporum spp, require activation by microsomal mixed-function oxygenases in order to produce injury in the tissues in which they accumulate One such compound isolated from M deserti, deisopropylngaione, causes necrotizing lesions in the liver, kidney and lung The native pteridophyte Marsilea drummondii contains thiaminase I at such a high level of activity that it can cause clinical thiamine deficiency in adult sheep which graze it at times of the year when it is growing profusely Potent diterpene esters (which have been found to be potent cocarcinogens in mice) are to be found in thymelaeaceous plants such as Pimelea spp One such compound, simplexin, also causes marked contraction of vascular smooth muscle, giving rise to the cardiopulmonary and hepatic circulatory disorder in cattle, known as St George Disease Carboxyatractyloside has recently been found to be the toxin in Xanthium spp The compound is a hypoglycaemic agent, an inhibitor of mitochondrial oxidative phosphorylation and causes acute liver necrosis Swainsona spp contain the a-mannosidase inhibitor trihydroxyindolizidine Consumption of the plants by animals results in the typical lysosomal storage disease a-mannosidosis Oxalate or acid oxalate ions in plants normally cause toxicity per se in grazing animals, but when present in low levels in various native and introduced grasses eaten by horses, they can produce negative calcium balance and secondary nutritional hyperparathyroidism within several months