bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hearing loss in rats caused by inhalation of mixed xylenes and styrene
Authors: Pryor Gordon T. , Rebert Charles S. , Howd Robert A. 
Published: October 2006

AbstractWe have reported that inhalation exposure of rats to toluene causes permanent hearing loss, e.g. Pryor et al. Neurobehav. Toxicol. Teratol. 5, 53–62 (1983). Therefore, it was of considerable interest to examine the ototoxic potential of two structurally related solvents—mixed xylenes and styrene—compared with that of toluene. Male, weanling Fischer‐344 rats were exposed to clean air or solvents in four identical 62.5 I Pfexiglas chambers. Exposures to 800, 1000, and 1200 ppm were daily for 14 hours/day and lasted 6 weeks for mixed xylenes, 3 weeks for styrene. An additional experiment with xylenes examined the effect of exposure for only 4 (1700 ppm) or 8 (1450 ppm) hours or for 8 (1450 ppm) hours on three consecutive days to compare the results with those obtained with toluene under comparable exposure schedules. Both xylenes and styrene caused marked hearing loss as assessed by behavioral (conditioned avoidance) and electrophysiologic (brainstem auditory‐evoked response) methods. Moreover, both solvents appeared to be more potent ototoxicants than toluene, as indicated by effective concentration, effective durations of exposure, and the range of frequencies affected.
The potentiation of the non‐behavioural effects of amphetamine by carbon disulphide
Authors: Caroldi Stefano , Magos Laszlo , Jarvis Jack , Forshaw Philip , Snowden Roger T. 
Published: October 2006

AbstractIn agreement with the inhibition of dopamine‐β‐hydroxylase by exposure to CS2, the extension of exposure time from 4 to 16 h increased dopamine concentrations in the hypothalmus and adrenals, and decreased noradrenaline concentration in the hypothalmus. The extension of exposure time also increased the toxicity of amphetamine. In conscious animals the stereotypic activity produced by 6.0 mg/kg and even that of 3.0 mg/kg amphetamine sulphate was suppressed by severe hyperthermia resulting in exhaustion, prostration and eventually death. A 16h exposure to CS2 did not increase the lethal or hyperthermic effects of amphetamine in rats anaesthetized with 60 mg/kg sodium pentobarbitone. In fact the CS2 exposed rats became more hypothermic than non‐exposed rats.
Early biochemical alterations in liver mitochondria from carbon tetrachloride poisoned rats
Authors: Villarruel M. C. , Fernandez G. , Aguilar E. G. , Castro J. A. 
Published: October 2006

AbstractCovalent binding of reactive metabolites of 14CCI4 were found 1 or 3 h after treatment with the solvent in the lipid and protein fractions of highly purified liver mitochondrial of rats. Most of the label was found in the phospholipid (PL) fraction, much less in cholesterol esters (ChE), and only minor quantities in other lipids. The reactive metabolites of 14CCI4 activated by isolated mitochondria interact mostly with ChE and far less with PL and other fractions. Both in vivo and in vitro covalent binding to PL is decreasing in the following order: phosphatidylethanolamine > diphosphatidylglycerol > phosphatidylcholine > sphingomyelin > lysophosphatidyl choline. No evidence of lipid peroxidation was found in liver mitochondrial lipids in the first 6 h and only a slight tendency of decrease in arachidonic acid concentration at 24 h. The incorporation of [14C] leucine in mitochondrial, microsomal or cytosolic proteins decreased as early as 1 h after treatment. These results, in agreement with previous reports suggest the existence of multiple sites in liver cells for the activation of CCI4. The transport of altered phospholipids and proteins and the inhibition of protein synthesis might contribute to the propagation of damage from the endoplasmic reticulum to other organelles.
Differential response of NADP‐linked hepatic aldehyde dehydrogenase toward taurine: Implication for behavioural effects of ethanol
Authors: Messiha F. S. 
Published: October 2006

AbstractThe effects of taurine, its initial precursor L‐cysteine, and the major metabolite taurocholic acid on two ethanol‐mediated responses in rodents were studied. Administration of a single dose of taurocholic acid reduced voluntary intake of a 5% ethanol solution by the rat. In the mouse, taurine had no effect on alcohol drinking or on the central depressant action of ethanol, as measured by the duration of ET‐produced loss of the righting reflex. Likewise, taurocholic acid and L‐cysteine did not significantly influence the duration of ethanol‐narcosis time from control mice. Also studied were the effects of acute and short‐term (7 or 10 days) administration of these compounds on hepatic ethanol and acetaldehyde metabolizing enzymes. Short‐term administration of an equimolar concentration of taurine enhanced endogenous NADP‐linked rat liver aldehyde dehydrogenase (L‐ALDH) as contrasted with inhibition of the same enzyme by L‐cysteine. Short‐term (7 days) treatment with L‐cysteine induced rat liver NAD‐linked ALDH, but acute (single dose) treatment did not. Taurocholic acid short‐term administration caused an induction and an inhibition of endogenous mouse liver alcohol dehydrogenase (L‐ADH) and L‐ALDH, respectively. The results suggest that taurine does not directly interact with ethanol. However, its major metabolite, taurocholic acid, may cause rapid metabolic conversion of ethanol to acetaldehyde by induction of L‐ADH, which is then slowly metabolized due to a concomitant inhibition of L‐ALDH. This may cause a build‐up of acetaldehyde and thereby produce adverse reactions similar to those resulting from the combination of disulfiram and ethanol.
Acute effects of isopropyl alcohol exposure on the middle ear mucosa
Authors: Ohashi Yoshihiro , Nakai Yoshiaki , Ikeoka Hiroshi , Koshimo Hiroyuki , Esaki Yusuke , Horiguchi Shun'Ichi , Teramoto Keiko , Nakaseko Hiroyuki 
Published: October 2006

AbstractGuinea pigs were exposed to 400 ppm or 5500 ppm of isopropyl alcohol (IPA) for 24 successive hours, and then middle ear mucosal samples in both proximal and distal sites to the eustachian tube were obtained for functional and morphological examinations. The ciliary activity was examined according to the photoelectric method of Ohashi and Nakai. The morphology of the middle ear lining was examined by transmission electron microscopy. The results showed that IPA at the allowable level of 400 ppm has an acute effect on the mucociliary system of the middle ear mucosa. Recovery from damage occurs within two weeks. At higher levels of exposure to IPA (more than 10 times the allowable level) moderate deterioration of the ciliary activity and severe damage of epithelial cells were observed and recovery within two weeks was not seen. It is concluded that IPA at the allowable level of 400 ppm does not cause significant middle ear disorders, but workers exposed to higher levels of IPA should be given careful otolaryngological examinations and follow‐up observations.
Effects of in vivo administration of detergents on the hepatic microsomal cytochrome P‐450 system in rat
Authors: Miura Yoshiro 
Published: October 2006

AbstractThe influence of in vivo administration of detergents on the hepatic microsomal cytochrome P‐450 system was studied in rat. Male Wistar rats were administered detergents, Emulgen 913 (50 mg or 100 mg kg−1 of body weight (B.W.)), or sodium dodecylsulfate (SDS, 25 mg or 50 mg kg−1 of B.W.) intraperitoneally once a day for 3 days. Cytochrome P‐450 content in liver microsomes was significantly decreased to 85% and 73% of control by the administration of 50 mg or 100 mg Emulgen, respectively, but the microsomal protein concentration was not changed by these administrations. The content of cytochrome P‐450 was also reduced to 76% and 70% of control by the administration of 25 mg or 50 mg SDS/kg of B.W., respectively. The total hydroxylation activity (the sum of ω‐ and (ω ‐ 1)‐hydroxylase activity) of laurate almost paralleled the decrease in cytochrome P‐450 in detergent‐treated rats. However, the ω/ω‐1‐hydroxylation ratio was not changed. These results suggest that the administration of these detergents lowered the level of cytochrome P‐450 species catalyzing ω‐ and (ω ‐ 1)‐hydroxylation of laurate to a similar extent. On the other hand, aminopyrine N‐ and p‐nitroanisole O‐demethylation activities in Emulgen 913‐treated rats was decreased while those in SDS‐treated rats did not change, though the content of cytochrome P‐450 was decreased by both administrations. Thus, it was demonstrated that the livers of rats responded to exogenous detergents in different manners.
Acute and subchronic toxicity of tetramethylcyclohexanes
Authors: Johannsen Frederick R. , Levinskas George J. 
Published: October 2006

AbstractThe acute oral toxicity in rats was estimated for seven isomers or isomeric ratios of tetramethylcyclohexane (TMCH). Lack of sufficient mortality at the highest dosage test (15.8 g/kg) precluded evaluation of an LD50 for mixed cis, trans‐isomers of 1,2,3,4‐TMCH, 1,2,3,5,‐TMCH, 1,2,4,5‐TMCH and 1,1,2,3‐TMCH, for the separate cis‐ or trans‐forms of 1,1,3,5‐TMCH or a 1:1 mixture of c,t−1,1,3,5‐TMCH and c,t−1,2,3,4‐TMCH. Mixed (c,t‐combined) isomeric TMCH was administered oraiiy to rats (30/group) and dogs (8/group) for 90 days at dietary levels of 0, 3000, 10 000 and 30 000 ppm TMCH and 0, 100, 300 and 1000 ppm TMCH, respectively. Administration of up to 30 000 TMCH to rats produced no discernible effects on survival, behavior, growth, food consumption, clinical blood picture or urine analysis. Absolute kidney weights of male but not female rats were elevated at all test levels. TMCH‐related microscopic lesions were confined to the kidney of male rats in all treated groups. These histopathologic changes were characteristic of tubular nephrosis. No treatment‐related effects were observed in groups of dogs fed up to 1000 ppm TMCH for 90 days.
Maternal toxicity, embryolethality and abnormal fetal development in CD‐1 mice following one oral dose of T‐2 toxin
Authors: Rousseaux C. G. , Schiefer H. B. 
Published: October 2006

AbstractAn experiment was undertaken to determine the teratogenic effect of oral administration of T‐2 toxin, a trichothecene mycotoxin. Firstly, a dose response study using 0,0.5, 1.0, 2.0, 3.0, 3.5 and 4.0 mg/kg T‐2 toxin in propylene glycol, on day 9 of pregnancy, was undertaken. Maternal deaths and toxicity was noted in the 4.0 and 3.5 mg/kg groups post‐toxin administration. These groups gained less weight throughout gestation than the rest of the groups, because no fetuses were found in the 4.0 mg/kg group and the 3.5 mg/kg group had significantly fewer fetuses than the remaining groups. The total fetal weight was similar among all groups with fetuses, and normal sex ratio of offspring was seen. More major and minor defects were seen in the 3.0 mg/kg T‐2 toxin treated group than any other group. Secondly, a day response trial using a single dose of 3.0 mg/kg T‐2 toxin given on either days 6, 7, 8, 10, 11 or 12 of gestation was undertaken. Maternal mortality, with placental hemorrhage, was observed. Fetal loss was greater in the T‐2 toxin treated groups than in the starved controls. The greatest number of dead term fetuses was seen in mice treated on day 9 of gestation. Normal sex ratios were present in the offspring. Major skeletal defects were more numerous in mice treated on day 7 of gestation, whereas minor defects, retardations and variants were more common in mice treated on day 8. It was concluded that a single oral dose of T‐2 toxin in propylene glycol is primarily maternotoxic and embryolethal, and that defective development was possibly secondary to maternal toxicity.
Evaluation of the nephrotoxic potential of styrene in man and in rat
Authors: Viau C. , Bernard A. , de Russis R. , Ouled A. , Maldague P. , Lauwerys R. 
Published: October 2006

AbstractThe urinary excretion of β2‐microglobulin, retinol‐binding protein and albumin was measured in 65 workers exposed to styrene at levels averaging 50 percent of the current threshold limit value (215 mg/m2) for 1–13 years (mean: 6 years). By comparison with a control group matched for age and socioeconomic status, no significant difference was observed in the urinary excretion of proteins. In rats, styrene was weakly nephrotoxic. No functional or morphological renal change could be disclosed in rats exposed to 565 mg of styrene/m3, 5 days/week for 13 weeks. The repeated i.p. injection of 1 g styrene/kg (1/5 of oral LD50) for 10 days induced only a slight tubular dysfunction as evidenced by a 5‐fold increase in β2‐microglobulinuria. Altogether, these epidemiological and experimental data suggest that the current threshold limit value for styrene (215 mg/m3) proposed by the American Conference of Governmental and Industrial Hygienists does not entail any risk of renal toxicity.
Inhalation toxicity of ribavirin in suckling ferrets
Authors: Hoffmann Saroita H. , Staffa Jeffrey A. , Smith Roberts A. , Craig Douglas K. , Parker George 
Published: October 2006

AbstractRibavirin is a broad‐spectrum antiviral agent useful for treatment of infants. To study the effects in developing mammalian lungs, four groups of jill ferrets and their litters were given whole body inhalation exposures for 6 h a day for 10 or 30 consecutive days to concentrations of 0 (vehicle control), 162, 355 or 620 mg/m3. The effects, including special lung observations in suckling kits, were evaluated after exposures at weaning and at puberty. First the high dose, then the mid dose jills developed lactation failure. Probably due to nutritional deficiency, approximately half of the mid dose and three quarters of the high dose kits were found dead or killed whilst moribund. There were no test compound‐related deaths in the control or low dose level groups. Reductions in body weight gain were observed in both 10 and 30 day exposed kits, and high dose kits actually lost weight as exposure continued. Some recovery was apparent in survivors. Some discoloration of the liver was seen in malnourished kits at necropsy. There were no gross or histopathologic lesions in the lungs or tracheas of suckling ferrets attributable to the test material. Ribavirin exposure had no effect on the lavageable cell pool, while lung DNA to protein ratios showed a mild, reversible, proliferative response in smaller kits. There were no differences in lung function between controls and low dose kits of either group. Effects seen in the higher dose groups are due to differences in size. While there may have been a real dose‐related enlargement of alveolar diameters at 40 days of age, this disappeared in males by puberty and did not seem toxicologically significant in females. The low dose, which corresponds to an exposure dose 4 to 6 times that used clinically, appeared to be a no‐effect level.
A rapid method for determining soot content of lungs in diesel‐exposed rodents
Authors: Henderson Rogene F , Waide James J. , Mauderly Joe L. , McClellan Roger O. 
Published: October 2006

AbstractA rapid optical method for determining the quantity of soot in the lungs of rodents exposed to diluted diesel exhaust has been developed. The method is nondestructive to enzymatic components of the lung, allowing dose and biochemical assays to be done on the same sample. The lung burdens of soot were determined by comparing the extinction of light at 620 nm of lung homogenates from exposed animals to that of lung homogenates containing spiked standards.
Hepatotoxicity induced by the herbicide atrazine in the rat
Authors: Maria C. Santa , Moreno J. , Lopez‐Campos J. L. 
Published: October 2006

AbstractThe hepatotoxicity of atrazine was investigated by studying clinical parameters related to hepatic function and by electron microscopy. Three groups to male albino rats (Wistar strain) received 100, 209 and 400 mg of atrazine/per kg of body weight/per day, for 14 days. One group received 600 mg atrazine/per kg of body weight/per day, for 7 days. At termination of dosing, the animals were sacrificed and blood was drawn for the determination of serum total lipids, glucose, alanine aminotransferase (ALT) and alkaline phosphatase (SAP). A dose dependent decrease in serum glucose concentration was observed in all the groups. In contrast, a dose relate increase in total serum lipids, was apparent at all dose levels studied. Activity of serum ALT and SAP increased approximately 60% and 200% respectively in rats given 600 mg atrazine/kg bw for 7 days. The liver was examined grossly and microscopically. Electron microscopy disclosed no changes in the hepatocytes of rats treated with the low dose (100 mg/kg bw). At high doses, electron microscopy revealed hepatocytic proliferation and degeneration of smooth endoplasmic reticulum, lipid accumulation and alteration of bile canaliculi proportional to dose and duration of treatment.
Respiratory and non‐respiratory lung function indices during the development and resolution of O,S,S‐trimethyl phosphorodithioate‐induced lung damage in the rat. A chemical model of adult respiratory distress syndrome
Authors: Nemery Benoít 
Published: October 2006

AbstractArterial blood gases and the pulmonary uptake of putrescine and 5‐hydroxytryptamine (5‐HT) were studied between 6 h and 18 days after the administration to rats of an oral LD50‐dose of the pneumotoxin, O,S,S‐trimethyl phophorodithioate (OSSMe), a potential impurity in several organophosphorus insecticides.Aortic blood was sampled under pentobarbitone anaesthesia for measurements of arterial pH, and partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). PaO2 was significantly decreased 4 days after OSSMe administration, i.e. at the time of maximum lethality and increases in wet lung weight. This was accompanied by a significant increase in PaCO2 and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear, PaCO2 was slightly increased 2, 6 and 12 days after dosing.The uptake of putrescine (1,4‐diaminobutane) and of 5‐HT was measured by incubating lung slices with several concentrations of [3H]‐putrescine and [14C]−5‐HT, so as to estimate the apparent kinetic parameters of uptake, Vmax and Km. The Vmax for putrescine‐uptake was significantly decreased 1,2,4,6 and 12 days after the administration of OSSMe. The Vmax for 5‐HT‐uptake was significantly increased 1 day and significantly decreased 4 days after OSSMe administration.The uptake of 5‐HT is an endothelial function, and the decrease in 5‐HT‐uptake at 4 days may reflect injury to the pulmonary vascular endothelium at this time. The uptake of putrescine probably reflects the function of the pulmonary (mainly alveolar) epithelium. Alveolar type I cells are the cellular targets for the toxic action of OSSMe, and their destruction is followed by type II cell proliferation. The early and prolonged decrease in putrescine‐uptake, therefore, suggests that this function is different in proliferating type II cells as opposed to quiescent type II cells.
Effects of altered exposure chamber pressure on the breathing pattern of conscious rats in nose‐only exposure tubes
Authors: de Madron E. , Mauderly J. L. 
Published: October 2006

AbstractRats exposed to inhaled toxicants while in plethysmographs having nose or neck seals may breathe against a negative pressure gradient during exposure. Breathing against negative pressure might affect the respiratory pattern and thus, the uptake or deposition of toxicant. The respiration of 10 conscious rats restrained in plethysmographic nose‐only inhalation exposure tubes having a neck seal, was measured during breathing against ambient, negative and positive pressures (0 to ± 7.5 cm H2O). Negative pressure increased respiratory frequency and reduced tidal volume, but minute volume was little changed. The estimated fraction of inspirate reaching the alveoli was reduced and inspiratory flow was increased. The magnitudes of these changes were small at typical exposure pressures, and the magnitudes of their effects on uptake and deposition would be expected to fall within the range of normal intersubject variability. Positive pressure tended to have effects opposite those of negative pressure.
Mutagenicity and cytotoxicity of n‐methyl‐2‐pyrrolidinone and 4‐(methylamino)butanoic acid in the Salmonella/microsome assay
Authors: Wells David A. , Thomas Harvey F. , Digenis George A. 
Published: October 2006

AbstractThe industrial solvent N‐methyl‐2‐pyrrolidinone (NMP) and its hydrolysis product, 4‐(methylamino)butanoic acid (N‐MeGABA), were examined for mutagenicity and cytotoxicity in the Ames Salmonella/microsome assay. In order to detect a broad range of possible mutagenic endpoints, the following strains were used in the assay: base‐pair substitution strains TA100, TA102 and TA104; frameshift strains TA97 and TA98; and repair proficient strains TA2638, UTH8413 and UTH8414. In the standard plate incorporation assay, six log‐linear doses of each compound were tested; doses ranged from 0.01 to 1000 μmol/plate for NMP, and 0.01 to 316 μmol/plate for N‐MeGABA. Neither compound was detectably mutagenic when tested in the presence and absence of metabolic activation by Aroclor‐induced rat liver S9. NMP did show significant responses with strains TA102 and TA104 that were less than two‐fold over background, but no clear dose–response relationships were evident. A preincubation modification of the assay was also performed, using strains TA98 and TA104. Mutagenic activity was not observed for NMP, while N‐MeGABA showed significant responses with TA104 but dose‐related mutagenicity was not established. Preincubation testing revealed both NMP and N‐MeGABA to be cytotoxic to the test population of Salmonella at the highest treatment doses.
A simplified protocol for the mouse bone marrow micronucleus assay
Authors: Garriott Michael L. , Piper Charles E. , Kokkino Andrew J. 
Published: October 2006

AbstractComplex and expensive protocols involving multiple sampling times have been proposed and recommended for the in vivo mouse bone marrow micronucleus assay. The purpose of this study was to determine whether a simplified procedure employing two identical exposures and a single sampling time would be equally effective at detecting chemical clastogens. Furthermore, the utility of the protocol was investigated for both intraperitoneal and oral routes of administration. The results obtained from a group of chemicals spanning the known time range for maximum frequency of micronucleus induction prove the effectiveness of this simplified protocol.
A subchronic inhalation study with unleaded petrol in rats
Authors: Vyskočil Adolf , Tušl Miloslav , Obršál Jindřich , Zaydlar Karel 
Published: October 2006

AbstractThe effect of intermittent 2 months' exposure to 2 g/m3 unleaded petrol on the hypothalamo‐pituitary‐thyroid‐adrenal system was evaluated by measuring hypothalamic noradrenaline (NA), serum corticosterone (CS), thyroxine (T4) and adrenal catecholamine (CA) levels in male rats. Serum CS and adrenal CA were increased and hypothalamic NA was decreased by exposure. No changes were observed in serum T4. Exposure induced an increase in spleen, kidney, liver and lung weights; weights of adrenals and hypothalamus were not changed. All the petrol‐induced effects depended on the length of exposure. Rats exposed to petrol gained less weight than controls. The results suggest a non‐specific stress response in the rat.