bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydropic change in rat liver induced by hexachloro‐1 : 3–butadiene
Authors: Lock Edward A. , Ishmael John , Pratt Iona
Published: October 2006

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.
Effect of chlorine dioxide and its metabolites in drinking water on fetal development in rats
Authors: Suh Duck H. , Abdel‐Rahman Mohamed S. , Bull Richard J.
Published: October 2006

The chlorination of surface waters is known to form trihalomethanes. Therefore, chlorine dioxide (ClO2) is being considered as an alternative disinfectant. This study was designed to determine the effect of chlorine dioxide and its metabolites, chlorite (ClO) and chlorate (ClO), on rat fetuses exposed in utero. Female rats were administered ClO2 at 0, 1, 10 and 100 mg 1−1 and ClO or ClO at 1 and 10 mg 1−1 daily in the drinking water for 2 1/2 months prior to and throughout gestation. Rats were killed on day 20 and fetuses examined for external, skeletal and visceral malformations. Slight decreases in weight gain during pregnancy were seen in the ClO2 administered groups. A significant dose‐response relationship in the decreases of the numbers of implants and live fetuses were observed in the ClO2 groups. Although there were increased incidences of resorptions in the ClO and ClO groups, no statistically significant increase was found in the groups. Fetal weight was significantly increased in the 100 mg 1−1 ClO2 group. Also, fetal length was increased in the 10 mg 1−1 ClO and ClO treatment groups. Skeletal defects, such as incompletely ossified or missing sternebrae, rudimentary ribs and incompletely ossified skull bones were increased in all treatment groups, but none were significantly different from the control group. A few cases of hypoplastic kidney, hydronephrosis and dextrocardia were observed in the treatment groups.
Subchronic feeding study in beagle dogs of N‐methylpyrrolidone
Authors: Becci Peter J. , Gephart Larry A. , Koschier Francis J. , Johnson William D. , Burnette Llewellyn W.
Published: October 2006

The potential toxicity of N‐methylpyrrolidone was evaluated following dietary administration for 13 weeks to male and female beagle dogs at dosage levels of 25, 79 and 250 mg per kg body weight per day. Body weight gain and food consumption, hematological and clinical chemical data, and ophthalmic, gross and histopathological examinations were used to study possible toxicological or pathological effects. No statistically significant treatment‐related effects that were judged to be biologically meaningful were seen in any parameters of either male or female animals exposed to N‐methylpyrrolidone at any dose level. However, a dose‐dependent decrease in body weight and increase in platelet count that correlated with increased megakaryocytes was observed. Serum cholesterol in males decreased with increasing doses.
The health hazards of formaldehyde
Authors: Wartew G. A.
Published: October 2006

Formaldehyde is ubiquitous in the environment. As an aqueous solution, it causes burns on contact with the skin and eyes, and the vapour is irritating to the eyes and respiratory system. It is a sensitizing agent and may affect susceptible individuals at levels below the current British TLV of 2 ppm. It has been tested for teratogenicity in several animal species by a variety of routes, but was not positive in any of the studies. Inhalation of the vapour has been shown to cause nasal cancer in rats and mice. However, epidemiological studies have failed to confirm whether or not the compound is carcinogenic in humans.
The possibility of food contamination with cadmium by means of coloured plastics
Authors: Preda N. , Popa Letitia , Ariesan Maria
Published: October 2006

By using spectrophotometric atomic absorption, the release of cadmium from some plastic materials (polyethylenes, PVC, polystyrene) used for manufacturing containers, wraps and household objects (which are coloured with pigments derived from cadmium compounds) was studied. Subchronic experiments (45 days) were carried out in white Wistar rats with extracts from cadmium—containing plastic in comparison with the pigment alone. The excreted cadmium in urine and the activity of some serum enzymes were determined. Histopathological changes of the main internal organs were observed. It was found that some pigments of the Papion type have the property of releasing cadmium in amounts exceeding the admitted sanitary levels, amounts which proved to be toxic, producing enzymic and histopathological changes in kidneys and testes.
Percutaneous absorption of an antimicrobial organosilicon quarternary ammonium chloride in rabbits
Authors: Siddiqui Waheed H. , Malek James R. , Stanton E. , Hobbs E. J.
Published: October 2006

The percutaneous absorption of an organosilicon quaternary ammonium chloride (14C)‐3‐(trimethoxysilyl)‐propyldimethyloctadecyl ammonium chloride (14C‐Si‐QAC) was studied in rabbits. Aqueous solution of 14C‐Si‐QAC was either applied to the intact, clipped back of animals for 10 days or administered by a single intravenous dose. Urine and feces were collected at 24‐h intervals and tissue concentration of radioactivity was determined at the end of the 10‐day study period. Elimination of 14C‐Si‐QAC after parenteral administration was slow and occurred by both urine and feces (13.5% in urine and 20% in feces). No radioactivity was found in the urine of dermally treated animals. Tissue concentrations of 14C were highest in the liver, lung and kidneys after i.v. administration. None was detected in tissues of dermally treated animals. The results showed that the absorption of 14C‐Si‐QAC through the skin of the rabbit was essentially zero. The potential absorption hazard of the use of this antimicrobial agent in contact with the skin is therefore considered to be insignificant.
Pharmacokinetics of Alcide®, a germicidal compound in rat
Authors: Scatina Joann , Abdel‐Rahman Mohamed S. , Gerges Samy E. , Alliger Howard
Published: October 2006

Alcide® is a germicidal compound which is currently being used as a liquid sterilizer. This agent has the ability to kill a wide range of bacteria, viruses and fungi in vitro within 1 min. The active ingredients in this sterilizer are sodium chlorite and lactic acid. The kinetics of 36Cl‐labelled liquid Alcide® were studied in rats. After oral administration, the peak plasma level was obtained in 8 h. The half life for 36Cl absorption from plasma was 8.03 h, corresponding to a rate constant of 0.086 h−1, while the half life for 36Cl elimination from plasma was 48.02 h, corresponding to a rate constant of 0.014 h−1. At 144 h, radioactivity was highest in plasma followed by lung, kidney, skin, bone marrow, stomach, ovary, duodenum, ileum, spleen, fat, brain, liver and carcass. The greatest amount of activity in whole blood was present in plasma. Subcellular distribution revealed that 85% of the activity in the liver homogenate resided in the cytosol. Seventy per cent of total activity in plasma was located in the trichloroacetic acid (TCA) supernant, with 30% bound to the precipitated protein fraction. Urinary excretion accounted for most of the 36CI eliminated. Radioactivity was excreted as chloride and chlorite in urine.
Carbon monoxide‐induced brain injury: Neurochemical studies after single and repeated exposures
Authors: Elovaara E. , Rantanen J.
Published: October 2006

Biochemical effects of a single and once‐repeated exposure to carbon monoxide (0.2% CO, 30 min) were studied in mouse brain. The effect of the severity of the first exposure on the brain reaction to the second exposure (0.2% CO, 30 min) was also studied after exposure to four different CO doses (0.2% CO for 0, 2 or 5 h, and 0.3% CO for 2 h). 1. The DNA content of brain decreased after single and once‐repeated CO exposures. The effect of the second exposure was greater than that of the first. 2. The changes in the glycosphingolipid synthesis of brain were measured as the specific rate of precursor incorporation into the two isolated galactolipid fractions, i.e., cerebrosides and gangliosides following a 2‐h pulse‐labelling with 3H‐galactose in vivo. The synthesis of cerebrosides was substantially inhibited for a short period after the first and the second exposures. A late compensatory over‐ecovery of synthesis was found only after the second exposure. The rate of galactose incorporation into gangliosides was not immediately depressed after CO exposure, but otherwise the changes were similar to those of cerebrosides. 3. The protein, phospholipid and cerebroside contents of brain were also affected in parallel fashion with the changes of DNA content. The content of gangliosides was increased after the first, but not after the second exposure. The enhanced reaction of brain to the second CO poisoning suggests the existence of sublethal brain cell injury which is produced by the first CO exposure and manifested by altered reactions to the second exposure.
Toxicology studies with a stable intravenous formulation of nitroglycerin
Authors: Anderson J. A. , McGuire E. J. , Watkins J. R. , Fitzgerald J. E. , de la Iglesia F. A.
Published: October 2006

The preclinical toxicologic profile of Nitrostat, a stable parenteral formulation of nitroglycerin, was determined in mice, rats, rabbits and dogs. Single‐dose i.v. studies in rodents yielded LD50 values of 17.3 and 18.2 mg kg−1 in male and female mice, and 24.4 and 23.2 mg kg−1 in male and female rats, respectively. Subacute i.v. studies in rats at doses of 2.5, 5.0 and 10.0 mg per kg per day, and in dogs at doses 1.0 and 3.0 mg per kg per day for two weeks, elicited minimal reactions. In rats, suppression of body‐weight gain and food consumption occurred among treated and vehicle‐control animals. Mild tissue irritation at injection sites was noted in treated and vehicle‐control groups. There were no clearly drug‐related clinical or pathological findings in dogs. In rabbits, repeated intravenous administration of Nitrostat did not induce significant local venous irritation. The results of these studies indicated that the stabilized parenteral formulation of nitroglycerin did not elicit unusual toxic properties in intravenous infusion studies.
Genetic toxicology association—Fall Meeting 1982
Authors: Skinner Michael J. , Sega Gary A. , Butterworth Byron E.
Published: October 2006

The Fall Meeting of GTA was held on 4 November 1982 at Cherry Hill, New Jersey. The theme of the program was in vivo/in vitro assays for unscheduled DNA synthesis (UDS) detection. The meeting was attended by about 100 members who heard three invited speakers, Gary Sega, Byron Butterworth and Michael Skinner, give talks on various aspects of UDS. These were complimented in the afternoon by a series of four contributed papers. The following are abstracts of the talks given by the main speakers.
Rapid high‐performance liquid chromatographic method for the estimation of toxicological levels of 25‐hydroxycholecalciferol (25‐OH D3) in human serum
Authors: Łukaszkiewicz Jacek , Kozłowski Kazimierz , Lorenc Roman
Published: October 2006

A reversed‐phase HPLC method for determination of 25‐hydroxycholecalciferol (25‐OH D3) in serum samples is described. The method involves extraction of 25‐OH D3 with hexane, followed by differential resolubilization in acetonitrile. The sample is then applied directly on the C18 bonded phase column of the liquid chromatograph, and developed in a acetonitrile‐water solvent system. In the range 12.5–400 ng, a linear relationship was observed between detector response and the amount of 25‐OH D3 placed on the column. Also, a very good correlation was observed between the amounts of 25‐OH D3 added to serum samples, and the calculated amounts. The method can be used for screening for toxicological levels of 25‐OH D3 in patients treated with high doses of vitamin D3.
The effect of chronic exposure to 100 ppm carbon monoxide on brain biomines, serum corticosterone and organ weights in rats
Authors: Vyskočil Adolf , Tušl Miloslav , Zaydlar Karel
Published: October 2006

The effect of chronic exposure to 100 ppm (0.01%) CO on pituitary‐adrenal activity was evaluated by measuring serum corticosterone and brain bioamine levels in the rat. Exposure to CO for 1 month induced a decrease in the brain serotonin levels. Serum corticosterone, brain dopamine and noradrenaline as well as the weight of the adrenal glands, lungs, spleen and liver were unchanged. After two months of exposure, serum corticosterone and brain serotonin levels were elevated and the liver weight was significantly lower. This suggests that at this chronic low concentration CO acts as a stressor, and the organism initiates a general defensive reaction. The effect of CO on the pituitary‐adrenal axis could be mediated by a central neuronal pathway.
Urinary excretion products after the administration of 14C‐acetaldehyde to rats
Authors: Kallama Seija , Hemminki Kari
Published: October 2006

Rats were injected with 120 μCi of 14C‐acetaldehyde containing carrier acetaldehyde, and the urinary excretion products were assayed by cation exchange chromatography, resolving five main peaks of radioactivity. Urine contained 6% of the dose of 14C‐acetaldehyde administered. The main urinary product of acetaldehyde, fraction 5, was produced via acetate. Acetate was also identified in the urine. Two cysteine adducts, probably isomeric metabolites of 2‐methylthiazolidine‐4‐carboxylic acid, were detected. They constituted about 2% of the radioactivity in the urine collected 48 h after the administration of 14C‐acetaldehyde. They appeared to retain a carboxylic group. When the reaction mixture of 14C‐cysteine and acetaldehyde was injected into a rat, the half‐lives of the two tiazolidine derivatives was 10 h. Only 13.6% of the radioactivity was detected in the urine suggesting ready metabolism of 2‐methylthiazolidine‐4‐carboxylic acid.
Regulation of a S(trans‐1,2‐dichlorovinyl)‐L‐cysteine‐induced renal tubular toxicity by glutathione
Authors: Hassall C. D. , Brendel K. , Gandolfi A. J.
Published: October 2006

The nephrotoxin S‐(1,2‐dichlorovinyl)‐L‐cysteine (DCVC) is cleaved in the renal tubules to produce a reactive electrophilic intermediate. If this intermediate is responsible for the toxicity, addition of the nucleophilic scavenger glutathione (GSH) should decrease toxicity, and depletion of tubular GSH should enhance toxicity. GSH was added to isolated rabbit renal tubules simultaneously with, 15 min before, and 15 min after the addition of DCVC. The active accumulation of the organic anion para‐aminohippuric acid (PAH) and organic cation tetraethylammonium bromide (TEA) was used as an index of renal toxicity. Incubation of renal tubules with 0.01–1 mM DCVC for 15 min decreased active transport, with complete inhibition at 1 mM. This was accompanied by a 50% decrease in non‐protein sulfhydryl concentration. The addition of GSH (6 mM) simultaneously with DCVC completely prevented any decrease in active transport. The addition of GSH (6 mM) to tubules in which active transport was inhibited by DCVC reversed the inhibition to 80% of control. Similar enhancement of active transport occurred when tubules isolated 1 h after in vivo exposure to DCVC at 20‐100 mg kg−1 were incubated with GSH (6 mM). Preincubation of renal tubules with GSH (5‐15 mM) made them more refractory to the DCVC‐induced decreased PAH and TEA transport. The inhibition of active transport by DCVC is enhanced if the tubular non‐protein sulfhydryl is first lowered by diethyl maleate or glycidol. Thus, the tubular GSH concentration appears to be an integral component in regulating the alterations in active transport caused by DCVC.
Concurrent exposure of lead and manganese to iron‐deficent rats: Effect on lipid peroxidation and contents of some metals in the brain
Authors: Malhotra Kiran M. , Murthy R. C. , Srivastava R. S. , Chandra Satya V.
Published: October 2006

Iron‐deficient rats were co‐exposed to manganese and lead to study lipid peroxide formation and contents of lead, manganese, copper, iron, zinc and calcium in the brain. Concurrent exposure to lead and manganese increased the lipid peroxidation potential of brain in iron‐deficient rats. The concentration of lead, manganese and copper in the brain of iron‐deficient rats increased to a greater magnitude after concurrent exposure to manganese and lead, compared with that observed after the exposure of either of the metals alone. Since copper is a potent inhibitor of transport ATPase in the brain, its significant increase, coupled with increased lipid peroxidation in the brain of iron‐deficient rats, may be responsible for enhanced susceptibility of iron‐deficient rats to the neurotoxic effects after the combined exposure to lead and manganese.
Induction of electrophysiological and morphological changes in sprague‐dawley rats fed tributoxyethyl phosphate
Authors: Laham S. , Long G. , Schrader K. , Szabo J.
Published: October 2006

The effects of a widely used trialkyl phosphate (TP), tributoxyethyl phosphate (TBOP), on the peripheral nervous system of Sprague‐Dawley (SD) rats were investigated. Male and female SD rats were administered this chemical by gavage over a period of 18 weeks (low dose: 0.25 ml kg−1; high dose: 0.50 ml kg−1). Electrophysiological changes observed at 18 weeks in all test animals included a significant reduction (P<0.001) in nerve conduction velocity and an important increase (P<0.001) of both relative (RRP) and absolute refractory period (ARP). Light and electron microscopic examination of sciatic nerve from all test animals showed the presence of degenerating myelin sheaths accompanied by axonal swelling. An advanced stage of degeneration was indicated by the presence of lamellated electron dense inclusions in unmyelinated nerve fibres.
Lead in cerebrospinal fluid and its relationship to plasma lead in humans
Authors: Cavalleri A. , Minoia C. , Ceroni M. , Poloni M.
Published: October 2006

Lead levels in whole blood, plasma and cerebrospinal fluid (CSF) were determined in 18 patients suffering from Amyotrophic Lateral Sclerosis (ALS) and in 21 subjects hospitalized for neurological investigations. No significant differences were found for blood, plasma and CSF lead concentration between the ALS group and the other patient group. The plasma lead‐CSF lead mean ratio was greater than 1 in both groups, while in subjects with a slight degree of blood‐CSF barrier impairment a significant decrease of the ratio was demonstrated. A significant relationship between plasma lead and CSF lead levels (r=0.405; p<0.01), but not between whole blood lead and CSF lead levels, was established. Lead levels in CSF were also age‐related (r=0.485; p < 0.05) in the group of patients not suffering from ALS. In subjects with normal blood‐brain barrier permeability, lead in plasma is a good indicator of CSF lead concentration.
Toxicity of hexachlorocyclopentadiene: Subchronic (13‐week) administration by gavage to F344 rats and B6C3F1, mice
Authors: Abdo K. M. , Montgomery C. A. , Kluwe W. M. , Farnell D. R. , Prejean J. D.
Published: October 2006

A 13‐week subchronic study was conducted by administering hexachlorocyclopentadiene (HCCP) in corn oil by gavage to groups of ten male and ten female F344 rats at doses of 150, 75, 38, 19, 10 or 0 mg kg−1, and to groups of ten male and ten female B6C3F1 mice at doses of 300, 150, 75, 38, 19 or 0 mg kg−1. The doses were administered once a day, five days per week for 13 weeks. Chemically induced deaths occurred at 150 and 300 mg kg−1 in rats and at 300 mg kg−1 in mice. A significant (P<0.05) depression in mean body‐weight change relative to controls was observed in male and female rats receiving ≥ 38 and ≥ 75 mg kg−1, respectively, and in male and female mice receiving 150 and 300 mg kg−1, respectively. There was a significant (P<0.05) increase in liver and kidney weight: brain weight ratios in the high‐dose female rats (75 and 150 mg kg−1) and female mice at all doses (19–300 mg kg−1). HCCP caused proliferative and inflammatory changes of the epithelia in the forestomach of male rats, and male and female mice receiving ≥ 38 mg kg−1 and in female rats receiving ≥ 19 mg kg dose level. Nephrosis characterized by proximal tubular dilation, cytoplasmic vacuolization, cytomegaly, karyomegaly and anisokaryosis occurred in male and female rats and female mice receiving ≥ 38 mg kg−1.
Pharmacodynamics and toxicity of chlorine in drinking water in the rat
Authors: Abdel‐Rahman Mohamed S. , Suh Duck H. , Bull Richard J.
Published: October 2006

Chlorine interacts with organic materials in surface water, leading to the formation of trihalomethanes, that may be carcinogenic. Studies were conducted to investigate the pharmacodynamics and toxicity of chlorine (0, 1, 10, 100 mg 1−1) in drinking water in rats. Blood glutathione (GSH) was significantly decreased after 6 months of treatment and this effect persisted after 1 year treatment in the 10 and 100 mg 1−1 groups. Treatment groups showed an increase in blood osmotic fragility. The acute study revealed that GSH was significantly decreased as early as 30 min after the administration of 30 and 120 μg chlorine. The effect was maintained up to 1 h. However, the GSH level returned to control value by 2 h. Blood osmotic fragility of the acute exposure was increased after 15 min and was without change after 30 min. Of the hematological parameters only the red blood cell count and hematocrit were significantly decreased in the 100 mg 1−1 group after 3 months of treatment. An examination of blood chloroform content in all the groups after 4, 6, 9 and 12 months showed no significant difference compared with the control. Chlorine administered chronically in drinking water for 3 months increased the incorporation of 3H‐thymidine into nuclei of rat kidney and testes in the 100 mg 1−1 group.
Mutagen formation in browning model systems
Authors: Shibamoto T.
Published: October 2006

A browning model system, consisting of diacetyl and ammonia, produced frameshift and base‐pair substitution mutagens when the system was heated over 20 min and 120 min, respectively. The major product was 2,4,5‐trimethylimidazole, which showed no mutagenicity toward Salmonella typhimurium strains TA98 and TA100 with or without metabolic activation. When furfural was reacted with nitrate under mild conditions (for 30 min to 3 h at 0–25°C and pH 2–7), it did not produce mutagenic nitrofuran derivatives. However, the ethyl ether extract obtained from the reaction mixture of furfural and nitrate with hydrochloric acid exhibited strong mutagenic activities toward S. typhimurium strains TA98 and TA100 in the presence of metabolic activation. The major product of this reaction mixture, 4‐nitrofurfural, exhibited no mutagenicity toward tester strains TA98 and TA100 with or without metabolic activation. Pure active mutagen(s) was (were) not, however, identified in either system.
Hair mercury levels of Japanese women during the period 1881 to 1968
Authors: Suzuki Tsuguyoshi , Hongo Tetsuro , Yamamoto Reiko
Published: October 2006

The hair samples of Japanese females during the period from 1881 to 1968 were obtained from various localities of the central area of Japan. Inorganic mercury levels were elevated in unwashed hair samples from prewar periods, especially during 1920s, while elevation of organic mercury levels was conspicuous during 1960s. The increase of inorganic mercury levels in samples from the 1920s is suspected to be due to mercury contamination of hair cosmetics, and increased organic mercury levels in the hair from the 1960s can be explained by active fish consumption.
Application of a radioactivity detector to the analysis of 14C‐Carmoisine metabolites by ion‐pair high‐pressure liquid chromatography
Authors: Tragni E. , Costa L. G. , Marinovich M. , Galli C. L.
Published: October 2006

14C‐Carmoisine was incubated under anaerobic conditions with a suspension of human faeces. Analyses of the incubation medium by high‐performance liquid chromatography (HPLC) attached to a radioactivity monitor (RAM) showed the same radioactivity profile as the urine and faeces of rats dosed with the same azodye (200 mg kg−1; 25 μCi). The analyses were carried out with a 5 μm RP‐C18 chromatographic column, using a linear gradient profile of different concentrations of water, methanol and an ion‐pair reagent. Five radioactive peaks were present in the radiochromatogram, in addition to unmodified Carmoisine. The major peak retained half of the specific activity of Carmoisine, and exhibited the retention time and the u.v. spectrum of authentic naphthionic acid. The results demonstrate the value and the advantage of using the in vitro preparation as a model to detect and to identify the metabolites of similar synthetic azodyes used as food additives.
The distribution of dermal tumorigens in coal liquids: Relationship of tumorigenicity and microbial mutagenicity
Authors: Holland J. M. , Larimer F. W. , Rao T. K. , Epler J. L. , Ho C.‐H. , Buchanan M. V. , Guerin M. R.
Published: October 2006

Polycyclic aromatic hydrocarbons and/or their pyrolle derivatives were found to be the primary contributors to the skin tumorigenicity of the neutral fractions of two coal oils. Mutagenicity of the neutral fraction in Salmonella test strains was found to be due primarily to polycyclic aromatics containing polar substituents. Thus, the chemical classes responsible for skin tumorigencity differ from those responsible for mutagenicity.
Effect of intermittent carbon monoxide inhalation on erythropoiesis and organ weights in rats
Authors: Chen K. C. , Lee Eun Woo , McGrath James J.
Published: October 2006

Sprague–Dawley rats were exposed to 450 ppm carbon monoxide (CO) for 6h per day, 5 days per week for 33 days. The effect of CO on reticulocyte count, hematocrit, hemoglobin concentration, body weight and selected organ weights was measured. Exposure to CO caused a three‐fold increase in the youngest reticulocyte population, concomitant with an increase in the total reticulocyte count. Despite continued CO exposure, reticulocyte number and distribution returned to normal by day 9, suggesting that reticulocyte response of the organism to CO had changed. Both hematocrit and hemoglobin concentrations began to increase 16 days after CO exposure and remained at the increased level for the duration of the exposure period. There were no changes in kidney, liver and adrenal weights throughout the course of study. However, spleen weight was increased after 5 days of CO exposure. Left and right ventricular organ weight ratios increased equally at the same time during the study. These results indicate that the increase in the young reticulocyte population and the subsequent increase in total reticulocyte count are the earliest erythropoietic responses to intermittent CO exposure and that CO‐induced polycythemia is associated with cardiac hypertrophy in rats.
Mutagenicity and chemical characterization of two petroleum distillates
Authors: Carver June H. , Macgregor Judith A. , King R. W.
Published: October 2006

To investigate if the Salmonella/microsome assay could reliably screen complex petroleum samples for their carcinogenic potential, two high boiling (700–1070 °F) petroleum distillates with known activity in a dermal carcinogenesis bioassay were fully characterized with respect to their hydrocarbon composition and polynuclear aromatic hydrocarbon (PNA) content and assayed for mutagenic activity. Mutagenicity assays were also carried out on the aromatic hydrocarbon aggregates separated from these oils by adsorption chromatography. The composition of the distillates differed substantially, and reflected the fact that they were derived from crude oils that were extremely divergent in hydrocarbon character. Both the distillate and aromatic samples consistently induced a very slight increase in revertant TA98 and TA100 colonies; however, an increase of 2–4‐fold over background was observed when the S‐9 concentration was increased 5–10 times that of the standard assay. The maximal response was less than that expected from the samples' known PNA content and observed potency in the dermal carcinogenesis bioassay. In the Salmonella/microsome assay, all samples inhibited the mutagenic activity of added benzo[a]pyrene. Discordance between the magnitude of the samples' mutagenic activity and their known PNA content may be related to direct or indirect inhibition of sample PNAs by other components of the complex petroleum fractions. Observed inhibitory effects support the use of elevated S‐9 concentration in the in vitro assays assessing the carcinogenic potential of petroleum‐derived materials.
Studies on the mechanism of toxicity of the mycotoxin sporidesmin. 2—evidence for intracellular generation of superoxide radical from sporidesmin
Authors: Munday R.
Published: October 2006

Formation of hydrogen peroxide, the dismutation product of superoxide radical, has been demonstrated in erythrocytes incubated with the mycoioxin sporidesmin. Erythrocytic thiols, both non‐protein and proteinbound, were depleted in the presence of sporidesmin, whilst haemoglobin was oxidized to methaemoglobin. Irreversible haemoglobin oxidation also occurred in these cells, shown by the formation of Heinz bodies; purified haemoglobin likewise suffered oxidative damage when incubated with sporidesmin in the presence of glutathione. Sporidesmin has previously been shown to generate superoxide radical in vitro; the erythrocytic changes induced by the mycotoxin, which are characteristically produced by compounds which generate ‘active oxygen’ species, suggest that it is also capable of generating this radical intracellularly.
Studies on the mechanism of toxicity of the mycotoxin sporidesmin 3—inhibition by metals of the generation of superoxide radical by sporidesmin
Authors: Munday R.
Published: October 2006

The mycotoxin sporidesmin has previously been shown to generate superoxide radical. This reaction involves autoxidation of the reduced form of the mycotoxin, a dithiol. In the present study, a number of mercaptide‐forming metals have been shown to inhibit superoxide formation from sporidesmin in vitro. Furthermore, these metals decreased the rate of sporidesmin‐induced hydrogen peroxide formation in erythrocytes and ameliorated the subsequent oxidative damage to these cells. These effects were found to be specific to sporidesmin; mercaptide‐forming metals did not inhibit the changes induced by compounds which are not dependent upon thiol groups for active oxygen generation. Zinc was one of the most potent inhibitors of superoxide generation from sporidesmin in these test systems; only mercury and cadmium were significantly more active. Salts of zinc are known to provide effective protection against the harmful effects of sporidesmin in vivo. The results of these studies provide a possible explanation for this effect.
A total hepatic induction index of metabolism for lipophilic xenobiotics
Authors: Boersma D. C. , Brownlee L. J. , Hollebone B. R.
Published: October 2006

A model for monitoring the hepatic ability to metabolize lipophilic xenobiotics is proposed. By identifying the behaviour of the mixed‐function oxidase system as the rate determining feature of the response, an index can be devised from three independent factors: (i) the rate of the catalyzed reaction at each enzyme site, (ii) the concentration of such enzyme sites per hepatocyte and (iii) the total number of active hepatocytes available. Use of the model was tested by administering an acute oral dose of 1,2‐benzanthracene to Sprague‐Dawley rats. The above factors were measured in practical terms, these being (i) enzyme activity per time per mg protein, (ii) the concentration of enzyme per unit microsomal protein as well as the concentration of microsomal protein per unit liver weight and (iii) ratio of liver weight to body weight. After statistical analysis, it was found that each factor obeyed a different response curve characterized by a different ratio of growth to decay exponents. The product of these four measurable and physiologically discrete phenomena at any dose is the Total Hepatic Induction index. Together, the parameters that make up our model provide a means for inter‐ and intra‐species comparisons as a response to various chemicals.
Effect of temperature on the inhibition of rat brain synaptosomal ATPases by DDT and its structural analogs
Authors: Chetty Sreeramulu C. , Aldous Charles N. , Desaiah Durisala
Published: October 2006

In vitro effects of DDT and its isomers or metabolites were studied on Na+‐K+‐ATPase and oligomycinsensitive (OS) Mg++‐ATPase activities at 17, 27 and 37°C in rat brain synaptosomes. Dicofol and methoxychlor were found to be more effective inhibitors of Na+‐K+‐ATPase and OS Mg++‐ATPase than DDT, DDD and DDE. Inhibition of OS Mg++‐ATPase by the compounds tested (except DDE) was found to be greater at 17°C than at higher temperatures (17>27>37°C), suggesting a negative temperature correlation trend. Na+‐K+‐ATPase was less sensitive to these compounds when compared with OS Mg++‐ATPase and the inhibition was greater at higher temperatures (37>27>17°C), suggesting a positive temperature correlation trend. Other DDT isomers and metabolites showed variable effects on Na+‐K+‐ATPase and OS Mg++‐ATPases. DDD, but not DDE, inhibited both enzyme activities and the inhibition was independent of temperature. No significant differences were observed in the inhibitory potencies of the various DDT, DDD or DDE ring substitutes studied. The present data indicate that DDT, dicofol and methoxychlor were more effective inhibitors of OS Mg++‐ATPase than Na+‐K+‐ATPase and that the inhibition of the former enzyme had a negative temperature dependence, a feature which parallels toxicity results in insects.
A methylmercury toxicity model to test for possible adverse effects resulting from chelating agent therapy
Authors: Kostyniak P. J. , Soiefer A. I.
Published: October 2006

A daily dosing model for methylmercury (MM) intoxication was developed for the purpose of testing for possible adverse effects resulting from the administration of complexing agents used in the treatment of MM poisoning. The dithiol complexing agents 2,3‐dimercaptopropanol (BAL) and meso‐2,3‐dimercaptosuccinic acid (DMSA) were chosen to test the discriminative ability of this model, since the former is contraindicated for MM poisoning and causes an increase in target organ MM burden, while the latter compound is known to be efficacious in reducing both toxicity and brain MM content. The basic design of the model called for daily observation of treated animals with identification of the following signs of MM intoxication: loss of body weight, onset of signs of toxicity, and mortality. The degree of toxicity was evaluated, and a toxicity score (0–5) was provided for each animal. A dose‐dependent decrease in body weight was found in MM‐treated mice. The latent period for development of signs of intoxication varied inversely with the dose rate. The rate of progression of severity of signs of intoxication was also dependent upon the dose. A dose rate of 14 mg Hg per kg per day was utilized to test the effects of BAL and DMSA on the onset and progression of signs of MM intoxication. Onset and progression of signs of methylmercury intoxication were similar for animals receiving methylmercury either alone or with administration of BAL at 2 mg per kg per day. Animals which received BAL at a dose rate of 20 mg per kg per day developed signs of intoxication significantly earlier. DMSA (500 mg kg−1) either alone or in combination with BAL (20 mg kg−1) protected animals against all signs of methylmercury poisoning. There was an insignificantly higher brain mercury concentration in animals receiving the 20 mg kg−1 BAL dose when compared to controls, whereas animals receiving the 500 mg kg−1 DMSA dose had brain concentrations one‐tenth that of matched control animals. The ability of DMSA to protect animals from the toxic effects of MM was confirmed, while BAL was shown to lack protective effects when given at the lower dose rate and to enhance MM toxicity when administered at the higher dose rate. This animal model of MM intoxication is useful in assessing both adverse and beneficial effects of new chelating agents on methylmercury intoxication.
Interaction of silicate dust with erythrocyte ghost membrane: In vitro studies
Authors: Singh Shivendra Vikram , Das Ballabh , Khan M. Firoze , Rahman Qamar
Published: October 2006

Composition of the erythrocyte ghost membrane obtained from slate‐dust‐lysed and hypotonically lysed erythrocytes were compared in vitro. The protein and cholesterol contents were unaltered, whilst phospholipid and glycosamine contents decreased significantly in the slate‐dust‐lysed preparation of erythrocyte ghost membrane. Na+, K+‐ATPase activity remained unchanged, whilst acetylcholinesterase activity was decreased slightly by slate dust treatment. Further, binding of silicic acid, dissolving out of slate dust, was observed with a component of erythrocyte ghost membrane protein having molecular weight around 90 000 daltons. The significance of the findings is discussed.
Normal organic and inorganic mercury levels in the human feto‐placental system
Authors: Suzuki Tsuguyoshi , Yonemoto Junzo , Satoh Hiroshi , Naganuma Akira , Imura Nobumasa , Kigawa Tomonori
Published: October 2006

To clarify the normal metabolism of mercurials in the human feto‐placental system, organic (or methyl) mercury and inorganic mercury were measured in maternal blood (MB), umbilical cord blood (UB), and chorionic tissues of the placenta (PC) and its blood vessels (PV), obtained from pregnant women just after delivery, as well as in fetal liver and fetal brain from induced abortion cases. Organic mercury was commonly detected in MB, UB, PC and PV, with slightly more elevated values in UB and PC than in MB, whereas inorganic mercury was detected in PC and PV, but not in MB and UB. In the fetal liver, 27–60% of mercury was in the form of inorganic mercury, whilst in four of five fetal brain samples, inorganic mercury was not detected. Additionally, fetal liver demethylation activity was studied in vitro. Incubation of methyl mercury with chopped fetal liver tissue for 24 h resulted in demethylation of approximately 1% of the methyl mercury.
A comparison of two methods of bleeding rats: The venous plexus of the eye versus the vena sublingualis
Authors: Angelov O. , Schroer R. A. , Heft S. , James V. C. , Noble J.
Published: October 2006

Of paramount importance to most toxicological studies in rats is the evaluation of hematological and clinical chemistry parameters. Currently, the principle bleeding method utilizes the venous plexus of the eye. This procedure has no detrimental effect on the general health of the animal and yields a sufficient quantity of blood, but has the potential disadvantage of damaging the eye. To avoid this disadvantage, a method was developed which is simple to perform, yields a sufficient quantity of blood and leaves the eye unimpaired. Samples are taken from the vena sublingualis. In order to compare the two methods, a study was initiated to determine the effect on body weight and food consumption as well as to compare hematological and serum chemistry parameters. The results showed that drawing blood from the vena sublingualis did not affect body weight or food consumption, and no significant differences were found in the hematological or serum chemistry values obtained by either method.
Administration of activated charcoal for the treatment of lantana poisoning of sheep and cattle
Authors: Pass Michael A. , Stewart Coralie
Published: October 2006

The use of activated charcoal for treating lantana poisoning was investigated. When 500 g of activated charcoal was given orally with toxic Lantana camara, it protected sheep against intoxication. Administration to sheep of 500 g of activated charcoal in 4 1 of electrolyte solution orally 6 days after the onset of lantana poisoning and then 4 1 of electrolyte solution the next day, was followed by recovery from the intoxication. Mortality was significantly higher in intoxicated sheep given only the electrolyte solution and in untreated sheep. Six cows with naturally occurring lantana poisoning were treated with 2–2.5 kg of charcoal in 20–30 1 of electrolyte solution given by stomach tube and all the animals recovered. It is recommended that sheep with lantana poisoning be treated orally with 500 g of activated charcoal in 4 1 of electrolyte solution, and that cattle be given 2 kg of charcoal in 20 1 of electrolyte solution. Supportive treatment for photosensitization and dehydration may also be required.
Vitamin E improves membrane lipid alterations induced by CCl4 intoxication
Authors: Martínez‐Calva I. , Campos‐Apáez A. , Rosales‐Vega E. , Mourellet Marisabel
Published: October 2006

The effect of pretreatment with vitamin E on membrane lipid alterations produced by the acute intoxication with CCl4 was studied. Rats were treated with an oral dose of CCl4 (0.4 g per 100 g body weight) and 24 h later the animals were sacrificed and liver plasma membranes isolated. After extraction, the membrane lipids were analysed by thin‐layer chromatography and quantitated by densitometry. The phospholipid: protein ratio determined in plasma membranes of CCl4‐treated rats was almost three‐fold higher than that found in control animals. Sphingomyelin (Sph) and phospharidyl choline (PC) increased, while phosphatidyl ethanolamine (PE) decreased in the plasma membranes isolated from the CCl4–treated group. Animals pretreated for 7 days with a daily dose of vitamin E (200 IU per kg body weight) showed a lower increase in the phospholipid: protein ratio (two‐fold) and the changes in Sph, PC and PE were lower. When the rats were pretreated with a higher dose of vitamin E (400 IU per kg body weight) for the same period, the lipid composition of plasma membrane was normal. These results indicate that vitamin E can protect against the alterations induced by CCl4 on the liver membranes. The protective action of vitamin E against CCl4 membrane damage is probably associated with its antioxidant properties.
The occurrence, metabolism and toxicity of cinnamic acid and related compounds
Authors: Hoskins John A.
Published: October 2006

Cinnamic acid is a compound of low toxicity, but its molecular structure and the known toxicity of similar molecules, such as styrene, have brought it to the toxicologist's attention. Commercially, its use is permitted as flavouring and it is ubiquitous in products containing cinnamon oil and to a lesser extent in all plants. The related aldehyde, alcohol and esters are all more toxic than cinnamic acid. Certain substituted cinnamates containing cyano and fluoro moieties are of particular interest because they inhibit mitochondrial pyruvate transport. The literature about this whole group of commercially important compounds is diverse and many key studies are in languages other than English. This review looks at the history and legal constraints, as well as the results of metabolism and toxicology studies.
Kidney toxicity of 3‐methylxanthine in the rat
Authors: Sellman R. , Klemi P. J.
Published: October 2006

The effects of 3‐methylxanthine, the pharmacologically active metabolite of theophylline, on the kidneys of Wistar rats after short‐term administration were studied. 3‐Methylxanthine was administered in oral doses of 0 (control), 50, 100 and 200 mg per kg per day for 1, 8 and 16 days. The kidneys were examined by light and electron microscopy. Tubular necrosis was noticed at a dose level of 100 mg kg−1 after 16 days and at a dose level of 200 mg kg−1 after 8 days. Elevated values of serum urea were found after 1 day of treatment with a dose of 200 mg kg−1 and after 16 days with a dose of 100 mg kg−1. Elevated values of serum creatinine were detected after 8 days of treatment with a dose of 200 mg kg−1. The results indicate dose‐ and time‐related renal failure following administration of 3‐methylxanthine.
Thallium replaces potassium in activation of the (Na+, K+)‐atpase of rat liver plasma membranes
Authors: Favari Liliana , Mourelle Marisabel
Published: October 2006

The capacity of thallium to substitute for K+ in activation of (Na+, K+)‐ATPase of liver plasma membranes was studied. Our results indicate that Tl+ can replace K+ in the activation of the (Na+, K+)‐ATPase of liver plasma membranes. In the presence of Na+, similar activation is obtained with Tl+ concentrations only 1/10 of those of K+. In all other aspects, the (Na+, K+)‐ and (Na+, Tl+)‐ATPases were found to be identical.
Hexachloro‐1, 3‐butadiene‐induced hydropic change in mouse liver
Authors: Lock Edward A. , Pratt Iona S. , Ishmael John
Published: October 2006

Hexachloro‐1, 3‐butadiene (HCBD) produced a time‐ and dose‐related increase in hepatic water content following i.p. administration to male Alderley Park (Alpk/AP) mice. The increase in liver water was maximal 1–2 days after a single dose of 50 mg kg−1 and had returned to normal by day 5. Associated with the increased water, there was a parallel increase in Na+ and K+ ions, with no overall change in intracellular cation concentration. Liver non‐protein sulphydryl content showed no consistent time‐related decrease after 50 mg kg−1 HCBD. Histopathological examination of the liver showed fine cytoplasmic vacuolation of periportal hepatocytes which was more marked following 100 or 200 mg kg−1 than 50 mg kg−1 HCBD. In one animal, following 200 mg kg−1 HCBD, the liver showed ballooning and degeneration of periportal hepatocytes. Ultrastructural changes were evident 4 h after 50 mg kg−1 and consisted of mitochondrial swelling in periportal hepatocytes, whilst pericentral hepatocytes appeared normal. By 16 h, marked mitochondrial swelling and some proliferation of smooth endoplasmic reticulum were evident in periportal hepatocytes. Male mice of the C57BL/10J and C3H strains appeared to be more sensitive to HCBD‐induced hepatic hydropic change than did the male and female Alpk/AP strain and male Balbc and DBA/2 J strains. It appears that HCBD or a metabolite causes disruption of mitochondria in periportal hepatocytes which results in an influx of water and ions into the cell without compromising the Na+ pump.