Postnatal toxicity of carbon monoxide after pre- and postnatal exposure

Rats were exposed prenatally through 21 days postnatally to 230 ppm carbon monoxide (CO). Offspring weights at 1 day and 5 days were depressed, and values for carboxyhemoglobin, hematocrit, hemoglobin, and heart weight: body weight ratio were elevated, compared to controls. At 21 days survival was markedly reduced in CO-exposed rats (36%) compared to controls (94%). These results, in view of other studies involving only prenatal or neonatal exposure at higher CO levels, suggest that neonatal and postnatal toxicity of CO may be enhanced by prenatal exposure.     

Carbon monoxide enhances development of hypertension in Dahl rats

The influence of carbon monoxide (CO) on the development of systemic hypertension was studied in Dahl rats selectively bred for susceptibility (DS) and resistance (DR) to NaCl-induced hypertension. This study was designed to examine the interactions among rat line (DS or DR), NaCl content of diet, and exposure to CO. The rats were exposed to 500 ppm CO or conditioned air, 21 hr/day, for 62 to 63 consecutive days. Carbon monoxide exposures affected blood pressure only in DS rats fed a high NaCl diet, where it enhanced the development of NaCl-induced hypertension. Whole-body weights were not affected by CO, but organ weight changes in the form of cardiomegaly ranging from 22% (DR, low NaCl) to 36% (DS, high NaCl), and splenomegaly ranging from 29% (DR, low NaCl) to 98% (DS, high NaCl) were observed. The mean equilibrium carboxyhemoglobin concentration was 42% in the CO-exposed rats. The hematologic responses to the CO exposures were elevated total hemoglobin and hematocrit.     

Resveratrol-associated renal toxicity.

Resveratrol, (3,5,4'-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram body weight per day. These included increased clinical signs of toxicity; reduced final body weights and food consumption; elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg resveratrol per kilogram body weight per day included reduced body weight gain (females only) and elevated white blood cell count (males only). Plasma resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg resveratrol per kilogram body weight per day in rats.     

Toxicity Studies of Epichlorohydrin in Sprague-Dawley Rats

ABSTRACT

Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but toxicity, at the higher doses, was evident by: 1) losses in body weight gain and organ weights, 2) reductions in food and water consumption, and 3) in the hematological and microscopic examinations in both study periods. Significant decreases in erythrocyte count, hemoglobin, and hematocrit levels were found in the high dose level in males after 10 and 90 days. Dose-related increases in kidney and liver weights were observed in both sexes at 25 mg/kg-day in the 90-day study and in various organs for both 19 and 46 mg/kg-day in the 10-day study.

Histopathological examination identified the forestomach as the primary target organ for both sexes and in both studies with significant dose-related increases in mucosal hyperplasia (acanthosis) and hyperkeratosis. Based on the data presented, a lowest observable adverse effect level (LOAEL) for oral exposure of Sprague-Dawley rats to epichlorohydrin is 3 mg/kg-day for 10 days and 1 mg/kg-day is suggested as the no observed adverse effect level (NOAEL) for a 90 day oral exposure. These conclusions were the same whether the lesions were analyzed for each sex individually or whether the data in each study was pooled.     

Inhalation toxicity of methylglutaronitrile in rats

Methylglutaronitrile (MGN) is a high-boiling (263 degrees C) solvent/intermediate used in the fiber industry. Twenty male rats per group were exposed nose-only to condensation aerosol/vapor concentrations of approximately either 5, 25, or 200 mg/m3 of MGN for 6 h/day, 5 days/week over a 4-week period. Ten rats/group were sacrificed one day after the final exposure and the remaining rats after a four-week recovery period. No effects were observed in clinical observations during the exposure period, but body-weight depression was observed in the 200 mg/m3 group. The 200 mg/m3 group showed minimal decreases in red blood cell count, hemoglobin, and hematocrit values accompanied by increases in reticulocytes. There were no other effects observed in clinical or pathologic evaluations in the study. A neurobehavioral battery of tests (including grip strength, functional observational battery, and motor activity tests) given at the end of the exposure and recovery periods showed no MGN effects. During the 4-week recovery, body weights in the 200 mg/m3 group returned to normal and the hematologic findings in all groups were normal. Based on the above findings of body weight depression at 200 mg/m3, the no-observed-adverse-effect level (NOAEL) for this study was considered to be 25 mg/m3.     

Effects of carbon monoxide inhalation on erythropoiesis and cardiac hypertrophy in fetal rats.

Pregnant rats were exposed to four CO concentrations over 21 days, and the effects of CO on fetal hemoglobin, hematocrit, heart weight, and body weight were measured. The exposure to 250 and 500 ppm of CO caused a sharp depression in fetal hemoglobin and hematocrit, coincident with a marked reduction of the weight of the fetuses, indicating a high vulnerability to CO of both fetal erythropoiesis and growth. The concentration of 125 ppm of CO did not affect fetal red blood cells, while 60 ppm of CO caused a slight increase in hematocrit. This low dose is below the threshold of an adaptive response in adult animals. The hearts of the fetuses exhibited a large increase in weight, which was even present in the 60-ppm group in contrast to reported data for adult animals. Since a severe anemia rather than polycythemia occurred, an increased blood viscosity cannot be responsible for the hypertrophic heart of the fetuses and consequently also of the adult animals, if the principal mechanisms for heart growth are identical in fetuses and adult animals. It is further unlikely that pulmonary hypertension causes the cardiac hypertrophy because the fetal lung circulation is only slightly developed. The reason of the heart weight increase therefore remains unknown.     

Time course of blood volume change with carbon monoxide inhalation and its contribution to the overall cardiovascular response

Adult male Sprague-Dawley rats inhaled 500 ppm CO continuously for 42 days in order to examine the blood volume response in a time course manner. Plasma volume as measured by Evan's blue dye dilution technique did not change significantly from the control value of 3.96% of body weight (BW). Total blood volume estimated using plasma volume and hematocrit increased steadily from 7.34% of BW to 11.69%, almost entirely as the result of a more than 2-fold increase in erythrocyte mass (3.42% increased to 7.55%). Absolute blood volume increased from 28.51 ml to 58.26 ml; normal growth contributed to this increase, i.e. BW increased from 350.0 g to 499.1 g. Real hematocrit determined by dye dilution increased from 46.5% to 64.6%, reaching a near-equilibrium level within 15 days. Hemoglobin concentration increased from 13.68 g/dl to 20.07 g/dl, and erythrocyte count increased from 6150000 per cubic mm to 9140000 per cubic mm. Minor changes in erythrocyte indices (i.e. mean corpuscular hemoglobin concentration and mean corpuscular volume) occurred during the 42 days. Concurrently, the weight of right ventricle increased more than left ventricle + septum, reflecting somewhat greater right-sided cardiomegaly. Increases in both ventricles were correlated with changes in blood volume and hematocrit. Plasma atrial natriuretic peptide activity increased 2.5 fold after 15 and 30 days of CO exposure, possibly reflecting increasing atrial stretch caused by increased blood volume. Like the polycythemic hypervolemic state of chronic hypoxic hypoxia, blood volume in CO hypoxia increases solely through addition of erythrocytes.     

Effects on splenic, hepatic, hematological, and growth parameters following high-dose poloxamer 407 administration to rats

The nonionic surfactant poloxamer 407, NF (PIuronic ^® F-127, NF) has previously been shown to produce marked hyperlipidemia in rats at a dose of 1.5 g/kg for greater than 96 h following a single intraperitoneal (i.p.) injection (Wout et al. J. Parenter. Sci. Technol., 46 (1992) 192–200). In an effort to characterize any potential toxicity of the polymeric vehicle to various organ systems in the rat following multiple i.p. injections, a dose of 0.33 g/kg per day (10% w/w solution) or 1.0 g/kg per day (30% w/w solution) of poloxamer 407 was administered once daily for 4 consecutive days. When compared to control (non-injected) animals, rats injected with 0.33 g/kg per day of poloxamer 407 did not show a significant (p > 0.05) increase or decrease in spleen, liver, or total body weight. A complete blood count (CBC) with a white blood cell (WBC) differential was performed on blood samples collected on day five from rats injected with poloxamer 407 at both doses. The CBC with WBC differentia] was conducted to assess any changes in the WBC count, percent lymphocytes (LY), percent monocytes (MO), percent granulocytes (GR), red blood cell (RBC) count, hemoglobin (HGB), percent hematocrit (HCT), and the mean corpuscular volume (MCV) following administration of poloxamer 407. Rats injected i.p. with a dose of 0.33 g/kgper day of poloxamer 407 for 4 days demonstrated a significant (p < 0.05) increase in the number of MO when compared to controls. Administration of 1.0 g/kg per day of poloxamer 407 to rats for 4 days demonstrated distinct splenomegaly when compared to non-injected control animals. In addition, a significant (p < 0.05) reduction in body weight and significant (p < 0.05) decrease in the percent LY, RBCs, HGB, and percent HCT were noted. Lastly, a significant (p < 0.05) increase in the number of WBCs and the percent MO was observed in this same group of rats. However, rats administered 1.0 g/kg per day of poloxamer 407 for 4 days were observed to have no detectable changes in the values of the MCV, the percent GR, or liver-to-body weight ratio when compared to control animals. Thus, repetitive i.p. injections of poloxamer 407 to rats at a dose of 1.0 g/kg per day for four days results in splenomegaly and a reduction in total body weight. Splenomegaly in rats administered poloxamer 407 at a dose of 1.0 g/kg per day resulted from red pulp expansion due to infiltration of macrophages which contained phagocytized lipids.     

Subchronic toxicity of trinitrotoluene in Fischer 344 rats rats

This study was conducted to evaluate the toxicity of trinitrotoluene (TNT) in Fischer 344 rats when administered in the diet for 13 weeks. Groups of 10 rats per sex received TNT at doses of 1, 5, 25, 125 or 300 mg/kg/day. Thirty rats per sex served as untreated controls. Toxicologic endpoints included clinical signs, body weight, food consumption, hematology, clinical biochemistry, organ weights and gross/histopathology. Toxic effects following 125 mg/kg/day or greater included decreased food intake and body weight gain, elevated serum cholesterol levels, and anemia (reduced hemoglobin, hematocrit and RBC counts). Splenomegaly, hepatomegaly/hepatocytomegaly and testicular atrophy with degeneration of the seminiferous tubular epithelium were also seen at 125 and 300 mg/kg/day. Hemosiderin-laden macrophages, congestion of the splenic red pulp, methemoglobin production indicative of the oxidizing activity of TNT and/or its metabolites, and the lack of bone marrow toxicity suggested hemolysis as the mechanism of anemia.     

Inhalation Toxicity of Methylglutaronitrile in Rats

Abstract

Methylglutaronitrile (MGN) is a high-boiling (263°C) solvent/intermediate used in the fiber industry. Twenty male rats per group were exposed nose-only to condensation aerosol/vapor concentrations of approximately either 5, 25, or 200 mg/m³ of MGN for 6 h/day, 5 days/week over a 4-week period. Ten rats/group were sacrificed one day after the final exposure and the remaining rats after a four-week recovery period. No effects were observed in clinical observations during the exposure period, but body-weight depression was observed in the 200 mg/m³ group. The 200 mg/m³ group showed minimal decreases in red blood cell count, hemoglobin, and hematocrit values accompanied by increases in reticulocytes. There were no other effects observed in clinical or pathologic evaluations in the study. A neurobehavioral battery of tests (including grip strength, functional observational battery, and motor activity tests) given at the end of the exposure and recovery periods showed no MGN effects. During the 4-week recovery, body weights in the 200 mg/m³ group returned to normal and the hematologic findings in all groups were normal. Based on the above findings of body weight depression at 200 mg/m³, the no-observed-adverse-effect level (NOAEL) for this study was considered to be 25 mg/m³.     

Ethylene glycol monobutyl ether: Acute, 9-day,and 90-day vapor inhalation studies in Fischer 344 rats

The acute 4-hr LC50 (with 95% confidence limits) for Fischer 344 rats was determined to be 486 (339 to 696) ppm of ethylene glycol monobutyl ether (EGBE) for males and 450 (315 to 645) ppm for females. Notable observations included loss of coordination, red stained urine, and enlarged discolored kidneys at 867 and 523 ppm. In a subsequent study, rats were exposed for 9 days (6 hr/day) to EGBE concentrations of 245, 86, 20, or 0 (control) ppm. There were significant depressions of red blood cell (RBC) count (approximately 20% below control values), hemoglobin (Hgb), and mean corpuscular hemoglobin (MCH) concentration and increases in nucleated erythrocytes, reticulocytes, and lymphocytes in males and females of the 245 ppm group. Decreased body weight gains and increased liver weights were also found. A 14-day postexposure recovery showed substantial reversal of the affected blood parameters. Similar, but less marked, hematologic effects were observed in rats exposed to 86 ppm of EGBE, while rats of the 20 ppm group were indistinguishable from controls. In a 90-day study, rats were exposed to EGBE concentrations of 77, 25, 5, or 0 ppm for 13 weeks (6 hr/day, 5 days/week). Slight, but statistically significant, decreases in RBC (13% below control) and Hgb, accompanied by an increase in MCH (11% above control) were observed in the 77 ppm-exposed females after 6 weeks. At the conclusion of the 90-day exposure regimen, the hematologic effects seen in the females had lessened (RBC was 7% below control) or returned to control value ranges. Furthermore, no treatment-related differences were found in body weight, organ weights, urine or serum chemistries, gross lesions, or microscopic lesions in males or females. There were no significant biological effects in rats exposed subchronically to 25 or 5 ppm. The subtle hematologic findings of these studies confirm the known RBC perturbations of EGBE.     

Subacute inhalation toxicity of aniline in rats: analysis of time-dependence and concentration-dependence of hematotoxic and splenic effects.

In this study, thirty male Wistar rats/group were exposed nose-only to mean analytical concentrations of 9.2, 32.4, 96.5, and 274.9 mg aniline/m3 using an exposure regimen of 6 h/day, 5 days/week for 2 weeks (days 0-11), followed by a 2-week post-exposure period (up to day 28). Serial sacrifices for specialized examinations were performed on days 0, 4, 11, 14, and 28. Clinical signs of toxicity, body weights, hematology, and clinical chemistry tests, including total iron in liver and spleen, splenic lipid peroxidation, organ weights, gross and histological changes in target organs were recorded. No mortality was observed during the study. Rats exposed to 96.5 mg/m3 and above displayed cyanosis, with no apparent progression during the exposure period. The predominant manifestation of toxicity was methemoglobin formation and associated erythrocytotoxicity. The changes observed included anemia, red blood cell morphological alterations (e.g., Heinz bodies), decreased hemoglobin and hematocrit, reticulocytosis, and effects on the spleen (splenomegaly, hemosiderin accumulation, and increased hematopoietic cell proliferation), which gained significance at 96.5 and 274.9 mg/m3. With regard to increased splenic extramedullary hematopoiesis, borderline effects occurred at 32.4 mg/m3. The total content of iron in spleen homogenates increased in a concentration-dependent and time-dependent manner with increasing duration of exposure. The maximum accumulation of iron in the liver and spleen exceeded the respective control levels by approximately 60% and approximately 500%, respectively. Splenic lipid peroxidation and total iron were highly correlated (r2 = 0.93) toward the end of the exposure period. A hepatic hemosiderosis was observed at 274.9 mg/m3. Thus, in regard to erythrocytotoxicity and associated increased splenic sequestration of erythrocytes, iron accumulation and lipid peroxidation 32.4 mg/m3 constitutes the no-observed-adverse-effect concentration (NOAEC). However, spleens of the 32.4 mg/m3 exposure group exhibited a minimal increase in extramedullary hematopoiesis. Exposure to 9.2 mg/m3 was not associated with any significant effect.     

Effects of phenylhydrazine or phlebotomy on peripheral blood, bone marrow and erythropoietin in Wistar rats

This study was conducted to characterize better the response of rats to blood loss and hemolysis and to incorporate automated methods into the routine evaluations of those responses. Serial phlebotomies of 1.5-2.0 ml of blood per day for 5 days, or intraperitoneal injection of 50 mg kg(-1) phenylhydrazine (PHZ) for 3 days, were used to cause anemia associated with blood loss or hemolysis, respectively. Maximum decreases in red blood counts were observed on Day 3 in PHZ-treated animals (68%) and Day 4 in blood-loss animals (35%). In the routine complete blood count (CBC), hemoglobin, hematocrit/hemoglobin ratio and erythrocyte indices could be used to discriminate between the two treatments. Free plasma hemoglobin in PHZ-treated animals resulted in marked elevations of mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) with a 2:1 hematocrit/hemoglobin ratio rather than the anticipated 3:1 ratio. Although both groups of animals had elevated white blood cell counts, PHZ-treated animals also had monocytosis and basophilia. Reticulocyte counts were more sensitive than erythropoietin (EPO) concentrations in predicting erythroid changes. Maximum mean reticulocyte values were ca. 24% in serially phlebotomized animals and >99% in PHZ-treated rats. Plasma EPO levels were 4-10-fold higher than EPO levels in urine, kidney or liver. Flow cytometric differentials of rat bone marrow using 2, 7-dichlorofluorescin successfully predicted erythroid hyperplasia in both experimental groups. Erythrocyte indices returned to normal within 14 days and the remaining CBC parameters were normal within 28 days for both treatment groups. Reticulocyte counts remained slightly elevated on Day 28, but were normal when assessed at Day 56 in blood-loss and PHZ-treated animals.     

INHALATION TOXICITY OF 4-ETHOXYANILINE (p -PHENETIDINE): CRITICAL ANALYSIS OF RESULTS OF SUBACUTE INHALATION EXPOSURE STUDIES IN RATS

This article addresses results from a single 4-h and repeated 1- and 4-wk inhalation exposure studies in Wistar rats with vapor and/or aerosol atmospheres of 4-ethoxyaniline (p -phenetidine). Groups of 10 rats/sex were exposed nose-only to mean analytical concentrations of 11.1, 86.2, and 882.6 mg p -phenetidine/m 3 using an exposure regimen of 6 h/day, 5 days/wk for 4 wk. Concentrations were selected based on results from a pilot study in which rats were exposed under identical conditions on 5 consecutive days for 6 h/day to mean analytical concentrations of 38.2, 133.0, and 1247.6 mg/m 3. In repeated exposure studies, the focus of endpoints was on hematotoxicity. The LC50 was not determined, but no rats died following a single 4-h exposure to 5085 mg/m 3 as a mixture of vapor and aerosol. No mortality was observed either in the 1- or 4-wk studies. Rats exposed to 882.6 mg/m 3 and above evoked characteristic signs of toxicity that included cyanosis, with no apparent progression of findings during the exposure period. Animals exposed to 86.2 mg/m 3 and above exhibited a concentration-dependent, significant increase in blood methemoglobin and reticulocyte counts as well as a significant decrease in hemoglobin, hematocrit, and red blood cell counts. Spleen weights were significantly increased in groups exposed to 133.0 mg/m 3 and above. Microscopic changes demonstrated an increased hematopoiesis (bone marrow smears) and splenic hemosiderosis at 86.2 and 882.6 mg/m 3 and a hepatic hemosiderosis only at 882.6 mg/m 3. These data suggest that the toxicity of p -phenetidine is similar to that of its structural analog aniline. Based on the erythrocytotoxicity occurring at 86.2 mg/m 3 and above, including the apparent reactive changes in bone marrow (increased erythropoiesis) and spleen (increased erythroclasia), the no-observed-adverse-effect level (NOAEL) of the 4-wk study was 11.1 mg/m 3 air and that of the 1-wk study was 38.2 mg/m 3 air. This difference in NOAELs is considered to be related to the selection of exposure concentrations rather than cumulative toxicity.     

Body and organ weights of rats exposed to carbon monoxide at high altitude

Although chronic exposure to carbon monoxide (CO) or high altitude produces pronounced cardiovascular changes in humans as well as animals, there is little information on the effects elicited by these stressors combined. Theoretical considerations, as well as data from acute studies, suggest that CO inhaled at high altitude may be more detrimental than CO inhaled at low altitude. The purpose of these studies was to construct a system in which CO and altitude could be controlled precisely, and to investigate the effects of continuous exposure to CO and high altitude on body weights and hematocrit ratios, as well as heart, spleen, adrenals, kidneys, and pituitary weights. Male, laboratory rats were exposed for 6 wk in steel barometric chambers to (1) 100 ppm CO, (2) 15,000 ft simulated high altitude (SHA), and (3) CO at SHA. Altitude was simulated by a system of gate valves and a vacuum pump, and measured by an altimeter. CO, from high-pressure cylinders, was introduced into the air supplying each chamber through a mass flow controller and measured by a nondispersive infrared (NDIR) analyzer. Although SHA had no affect on left ventricle plus septum (LV + S), adrenal, spleen, or kidney weights, SHA decreased body weights, and increased hematocrit ratios, as well as right ventricle (RV), total heart (HT), and pituitary weights. CO had no affect on body weights, RV, HT, adrenal, spleen, or kidney weights, but CO increased hematocrit ratios and LV + S weights. There was no significant interaction between SHA and CO on any parameter except kidney weight. These results indicate that, in general, the effects produced by 15,000 ft SHA are not intensified by exposure to 100 ppm CO.     

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene administered by oral gavage to Sprague-Dawley rats

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats to meet the needs of the U.S. Environmental Protection Agency for toxicity data on this chemical for use in their determination of possible health risks related to human exposure. 1,2-Dichlorobenzene was administered at doses of 37.5, 75, 150, and 300 mg/kg/day (10-day), and 25, 100, and 400 mg/kg/day (90-day) in corn oil by oral gavage; control animals received corn oil. At time of sacrifice, gross necropsies were performed and selected tissues were weighed and prepared for histological evaluation. Blood was taken for hematology and clinical chemistries. In the 10-day study, exposure of 300 mg DCB/kg body weight to male rats resulted in a statistically significant decrease in final body weight, organ weights (heart, kidneys, spleen, testes, and thymus), and relative organ weights (spleen and thymus). A significant increase in absolute and relative liver weights was also noted in this dose group. Males also displayed significant increases in water consumption (300 mg/kg group), ALT (300 mg/kg) and leukocyte count (150 and 300 mg/kg). A significant increase in the incidence of hepatocellular necrosis was seen in the 300 mg/kg group of males compared to controls. In the 90-day study, male rats exposed to 400 mg DCB/kg displayed a statistically significant decrease in body weight, organ weight (spleen), and relative organ weight (spleen). The absolute weights of kidney and liver and the relative weights for heart, kidney, liver, lung, brain, and testes were increased significantly for this dose group. The absolute and relative weights of both the kidney and liver were significantly increased in the female 400 mg/kg dose group. The only clinical chemistry parameters statistically different than control were increased ALT (100 and 400 mg/kg groups), BUN and total bilirubin in the male 400 mg/kg group and total bilirubin in the 400 mg/kg female group. Histopathological evaluation showed hepatocellular lesions associated with DCB treatment which included centrolobular degeneration and hypertrophy, and single cell necrosis in male and females receiving 400 mg DCB/kg. The NOAEL observed in this study is 25 mg/kg/day.     

Zinc prevents hematological and biochemical alterations induced by static magnetic field in rats

The present study was undertaken in order to investigate the effect of subchronic exposure of rats to static magnetic field (SMF) and/or zinc treatment on the selected hematological and biochemical parameters. Metallothioneins (MT) and zinc content in kidney and liver were studied. The exposure of rats to SMF for 1h/day during 30 consecutive days induced an increase in hemoglobin concentration, white blood cell count (WBC), red blood cell count (RBC) and platelet number. By contrast, hematocrit remained unchanged. The same treatment also increased the serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. However, the creatinine and urea concentrations were similar to those of controls. On the other hand, renal and hepatic zinc levels were not altered in SMF treated-rats. SMF exposure induced MT synthesis in the liver and kidney. Zinc administration (40 mg/l for 30 consecutive days, in drinking water) had no effect on hematological and biochemical parameters. However, hepatic and renal zinc content and MT levels were increased. Zinc prevented the increase in serum transaminase activities, and WBC and platelet counts induced by SMF. However, the elevation of the LDH, hemoglobin and RBC levels induced by SMF exposure was not suppressed. MT concentrations in both tissues were potentiated by zinc administration in SMF-exposed rats. It is suggested that zinc supplementation could prevent toxic effects of SMF probably by its anti-oxidant properties.     

Lack of effects of nose-only inhalation exposure on testicular toxicity in male rats.

Reductions in testicular mass, sperm motility, and mating frequency have been attributed to the stresses caused by confinement of Sprague-Dawley male rats in nose-only inhalation exposure tubes. Testicular changes, including an increase in testicular atrophy, have been detected at an increased incidence in male rats used in inhalation studies as compared with rats of the same age and strain used in oral toxicity studies. This study was designed to determine whether nose-only exposure of male rats caused testicular toxicity under conditions of cooling of the exposure room and appropriate acclimation to the exposure tubes. In order to acclimate the rats to the nose-only inhalation exposure apparatus, all male rats were placed in the exposure tubes for at least four successively increasing time intervals (15, 30, 45, and 60 min) on 4 separate days, with a rest period of approximately 48 h between the first and second acclimation. Twenty male rats were exposed nose-only to filtered air for approximately 2 h per day for 28 days before cohabitation and continuing throughout a 14-day cohabitation period. To reduce thermal stress, the exposure room temperature was maintained at 64 to 70 degrees F. Twenty control rats were housed in the same room as the exposed rats but were not placed in exposure tubes. End points monitored were body weight, testicular weight, sperm count, sperm motility, and histopathology of the testes, epididymides, prostate, and seminal vesicles. The control rats gained weight more rapidly than the exposed rats. All the rats in both groups mated successfully, and testicular weights, normalized to body weight, were similar for both groups. More importantly, there were no microscopic changes that could be considered an adverse effect on the reproductive tissues in the male rats placed in exposure tubes. Thus, nose-only exposure for up to 2 h per day for a total of 42 days did not cause adverse effects on the reproductive organs, fertility, or reproductive performance of male rats under the conditions of this study.     

Evaluation of subchronic inhalation toxicity of dimethyl disulfide in rats

This study was carried out to investigate the potential subchronic inhalation toxicity of dimethyl disulfide (DMDS) via whole-body exposure in F344 rats. Groups of 10 rats of each sex were exposed to DMDS vapor by whole-body exposure at concentrations of 0, 5, 25, or 125 ppm for 6 h/day, 5 days/wk for 13 wk. All the rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. At 25 ppm, a decrease in the body weight gain, food intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) was observed in the males, but not in the females. However, at 125 ppm, a decrease in the body weight gain, food intake, and thymus weight and an increase in the weights of adrenal glands were observed in both genders. Serum biochemical investigations revealed a decrease in the AST, ALT, BUN, creatine phosphokinase (CPK), and triglyceride levels and an increase in the glucose level. In contrast, no treatment-related effects were observed in the 5 ppm group. The toxic potency of DMDS was slightly higher in males than that in females. In these experimental conditions, the target organ was not determined in rats. The no-observed-adverse-effect concentration (NOAEC) was found to be 5 ppm, 6 h/day for male rats and 25 ppm, 6 h/day for female rats.     

Evaluation of Subchronic Inhalation Toxicity of Dimethyl Disulfide in Rats

This study was carried out to investigate the potential subchronic inhalation toxicity of dimethyl disulfide (DMDS) via whole-body exposure in F344 rats. Groups of 10 rats of each sex were exposed to DMDS vapor by whole-body exposure at concentrations of 0, 5, 25, or 125 ppm for 6 h/day, 5 days/wk for 13 wk. All the rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. At 25 ppm, a decrease in the body weight gain, food intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) was observed in the males, but not in the females. However, at 125 ppm, a decrease in the body weight gain, food intake, and thymus weight and an increase in the weights of adrenal glands were observed in both genders. Serum biochemical investigations revealed a decrease in the AST, ALT, BUN, creatine phosphokinase (CPK), and triglyceride levels and an increase in the glucose level. In contrast, no treatment-related effects were observed in the 5 ppm group. The toxic potency of DMDS was slightly higher in males than that in females. In these experimental conditions, the target organ was not determined in rats. The no-observed-adverse-effect concentration (NOAEC) was found to be 5 ppm, 6 h/day for male rats and 25 ppm, 6 h/day for female rats.