The acute oral toxicity of isomeric monobutylamines in the adult male and female rat

The acute oral LD₅₀ values of n-butylamine, isobutylamine, sec.-butylamine, and tert.-butylamine were determined in both male and female Sprague-Dawley CD rats. Signs of toxicity observed after single oral doses of the monobutylamines included sedation, ataxia, nasal discharge, gasping, and salivation followed by convulsions and death at the higher dose levels. Gross pathological examination of animals that died after the monobutylamine treatment revealed pulmonary edema. The LD₅₀ values for the monobutylamines were calculated by the probit method of D. J. Finney (1971, Probit Analysis, 3rd ed., Cambridge Univ. Press, Cambridge). No significant sex-related differences were noted. The 14-day, po single-dose LD₅₀ values (mg/kg body wt) were: n-butylamine, male 365.4, female, 382.7; isobutylamine, male, 224.4, female, 231.8; sec.-butylamine, male, 157.5, female, 146.8; and tert.-butylamine, male, 82.3, female, 78.1.     

Acute and subacute toxicity of cytochalasin E in the rat

Cytochalasin E, a minor toxic metabolite of the fungus Aspergillus clavatus, is acutely toxic to rats, mice, and guineapigs. The LD50 values for a single ip administration of cytochalasin E were: 1-day-old rats, 0.98 mg/kg; adolescent rats, 2.60 mg/kg; mice, 4.60 mg/kg, and guinea-pigs, 0.5–1.5 mg/kg. The toxicity of cytochalasin E was reduced in adolescent rats when administered orally (LD50 9.10 mg/kg) and was increased when administered by the intrathoracic route (LD50 1.30 mg/kg). Rats receiving a fatal ip dose of cytochalasin E died within 2–18 hr with 2–3 ml fluid in the peritoneal cavity. Intrathoracic administration of cytochalasin E killed rats within 2–8 hr and resulted in accumulation of 2.5–3.5 ml pleural fluid. Rats receiving the toxin orally died within 4–18 hr with 1.0–1.5 ml gastric fluid. Histopathologic examination revealed congestive degenerative changes, necrosis of liver, kidney, spleen, pancreas, and small intestine, brain edema, pulmonary hemorrhages, and injury to vascular walls.     

Acute and subacute inhalation toxicity of diborane in male ICR mice

 To clarify the toxicity of diborane, we conducted acute (15 ppm for 1, 2, 4 or 8 h) and subacute (5 ppm for 2 or 4 weeks) inhalation studies on ICR mice. The concentration resulting in a 50% kill after 4 h exposure was 31.5 ppm. Body weight gain was suppressed and the lung weight was increased in diborane-exposed mice in both acute and subacute studies. In the acute study, diffuse pan bronchiolitis-like lesions developed in the lung in various degrees depending on exposure time, which can be pathologically characterized as infiltration of inflammatory cells into the terminal bronchioles and surrounding alveoli, pulmonary congestion and bleeding and/or edema. In the subacute study, we observed lymphoid hyperplasia in the perivascular and peribronchial areas, and infiltration of macrophage and plasma cells into the alveoli. In the mice exposed for 4 weeks, the lesions were more severe than in those exposed for 2 weeks, consisting of hyperplasia and desquamation of Clara cells. In the nasal cavity, we saw mucous exudate and inflammatory cells, suggesting irritation caused by diborane. The histopathological findings, except for the respiratory organs, did not reveal any exposure-related changes. No significant changes were seen in hematological and serum biochemical examinations either. In conclusion, the target organ of diborane inhalation is the respiratory organs, particularly the lung. Further inhalation experiments are essential to investigate the safety exposure levels of diborane. Received: 31 May 1994 / Accepted: 3 November 1994     

Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice

 Using male ICR mice, the LC₅₀ and acute and subacute inhalation toxicity of dichlorosilane (SiH₂Cl₂, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC₅₀ of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH₄), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS. Received: 10 April 1995 / Accepted: 18 September 1995     

Subacute toxicity of trichloroacetic acid in male and female rats

Trichloroacetic acid, TCA, is a water chlorination by-product similar to dichloroacetic acid, DCA. Because DCA has been shown to have effects on intermediary metabolism, TCA was tested to determine if it possesses similar capabilities. The effects were more pronounced in females. High doses of TCA (2.45 mumol/kg three times) decreased plasma glucose and lactate concentrations and liver lactate concentration. DCA had similar, less pronounced effects. In males DCA and TCA each decreased plasma lactate concentrations. Rats were exposed to TCA in drinking water for 14 days. The highest concentration (2.38 g/l) caused decreases of water and food consumption and loss of body weight. At 7 days females had decreased urine volume accompanied by a modest increase of urine osmolality, resulting in a significant decrease of excretion of solute. Concentrations of glucose in plasma and lactate in tissues were not significantly affected by this subchronic TCA exposure. These results indicate that TCA may have effects on intermediary metabolism similar to those of DCA.     

Comparative subacute toxicity of all-trans- and 13-cis-retinoic acid in Swiss mice

Swiss mice were treated once a day for 21 days with all-trans- or 13-cis-retinoic acid administered ip or po. The LD50 of all-trans-retinoic acid was 31 mg/kg ip and 1100 mg/kg po; the LD50 of 13-cis-retinoic acid was 140 mg/kg ip and 26,000 mg/kg po. However, after 21 consecutive days of treatment, fractured bones were observed in treated animals at all tested doses of 13-cis-retinoic acid and at doses of all-trans-retinoic acid higher than 3 mg/kg ip or 10 mg/kg po. By either route of administration, 13-cis-retinoic acid produced the same number and incidence of fractures at doses three to five times that of all-trans-retinoic acid administered by the same route. Treatment with 13-cis-retinoic acid ip resulted in a dose-related decrease in the red blood cell count, but ip administration of all-trans-retinoic acid did not. The concentration of albumin, the serum transport protein for these compounds, was changed only after low oral doses of all-trans-retinoic acid. The appearance of fractured bones was not always associated with elevated plasma alkaline phosphatase concentrations. Based on these parameters of toxicity, 13-cis-retinoic acid was less toxic than all-trans-retinoic acid.     

Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats

The extensive use of copper oxide nanoparticles (CuO‐NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO‐NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO‐NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively. Blood analysis, tissue aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acetylcholinesterase, superoxide dismutase, catalase, lipid malondialdehyde and reduced glutathione assays, and histopathology of the tissues were carried out. The higher dose treatments of the acute and subacute study caused significant alterations in biochemical and antioxidant parameters of the liver, kidney and brain tissues of the rat. In addition, histopathological evaluation of these three organs of treated rats showed significantly high abnormalities in their histoarchitecture when compared to control rats. We infer from the results that the toxicity observed in the liver, kidney and brain of treated rats could be due to the increased generation of reactive oxygen species by CuO‐NPs.     

Ninety-day toxicity of photomirex in the male rat.

Photomirex (8-monohydromirex) is a demonstrated environmental contaminant and was observed in previous short-term studies to produce lesions in the liver, thyroid and testes of male rats. The present study was undertaken to confirm those observations and to determine the effects after a longer period of exposure. Male rats were fed photomirex for 13 weeks at levels of 0.20, 1.0, 5.0, 25 and 125 ppm in the diet. Deaths were observed in animals receiving the highest dose. Decreased body weight gain and food intake were also observed in that group. Liver weights were increased at 5.0 ppm photomirex and higher. Photomirex caused changes in several biochemical parameters including serum sorbitol dehydrogenase and hepatic aniline hydroxylase activities. Dose-related histological abnormalities were observed in the thyroid and liver starting at the lowest dose level. These results confirm earlier findings and show that photomirex is a potent hepato- and thyrotoxin.     

Comparative subacute effects of dietary raw soya flour on the pancreas of three species, the marmoset, mouse and rat

Subacute changes induced in the pancreas by raw soya flour have been studied in three species. The raw soya flour was fed to male Sprague-Dawley rats and male CD-1 mice for 2, 4 or 8 days at a level of 50% (w/w) in the diet, and to male and female marmosets for 2 or 7 days at 20% (w/w) in the diet. The stathmokinetic method was used to study mitotic activity in the pancreas, and mean acinar cell area was calculated using an image analysis system. The relative weight of the pancreas in the rat and mouse increased during dosing, but that of the marmoset did not. No proliferative or trophic effects were observed in marmoset pancreas, but in both the mouse and rat a transient increase in mitotic activity was followed by a steady increase in acinar cell size.     

The acute toxicity of four trihalomethanes in male and female rats

The acute toxicity of chloroform, bromodichloromethane, chlorodibromomethane, and bromoform was investigated in rats. The clinical signs observed following single oral doses of the test compounds were sedation, flaccid muscle tone, ataxia, piloerection, and prostration. Gross pathological examination revealed liver and kidney congestion. Median lethal doses (LD50) of the four trihalomethanes were calculated using the probit analysis. While male rats appeared to be more susceptible than the females to the lethal effect of chloroform (LD50 in mg/kg: male, 908; female, 1117) and bromodichloromethane (LD50: male, 916; female, 969), the females were found to be more sensitive than the males to chlorodibromomethane (LD50: male, 1186; female, 848) and bromoform (LD50: male, 1388; female, 1147).     

The toxicity of gossypol to the male rat

When (±) gossypol acetic acid was administered to male Sprague-Dawley rats for 26 weeks, the most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Minor biochemical changes were noted at this dosage level. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a “no effect” level.     

Adaptation to nephrotoxic effects of cephaloridine in subacute rat toxicity studies

The nephrotoxic effect of single iv daily doses of cephaloridine in rats for 10 to 15 days was investigated. Urine and serum samples and kidneys were analyzed 24 hr after the last injection. A circadian rhythm and dose-dependent increase of lactic dehydrogenase, alkaline phosphatase, and aminopeptidase occurred in the urine within the first 3 days. Nearly normal values were found after 10 days of application consistent but not correlating with a small degree of tubular injury as determined from the percentage of injured tubules in alkaline phosphatase-stained frozen sections. Measurements of the number of nucleated cells in the epithelium of proximal tubule cross sections and the number of tubular casts indicated an initial phase of cell degeneration and tubule necrosis followed by a phase of regeneration with young cells which tolerate larger doses of the nephrotoxic compound (up to twofold) than the original epithelium. This change of tubule cells was not reflected in the lactic dehydrogenase, aldolase, aminopeptidase, and/ or alkaline phosphatase content of the kidneys. Apparently the young cells in kidneys of rats injected daily released, as a nephrotoxic response, less lactic dehydrogenase into the urine than kidney cells 24 hr after a single dose.     

Comparative toxicities of dietary caffeine and theobromine in the rat

Caffeine, incorporated into pulverized Purina Rat Chow at a concentration of 0.5%, was fed to male Sprague-Dawley rats for 7 or 8 wk and the effects were compared with those of 0.8% dietary theobromine, fed to male rats for 7 wk. Both dietary methylated xanthines produced significant decreases in food consumption and body-weight gain when compared to their respective control groups. Food consumption of caffeine-fed rats was 57.2% of controls and for theobromine-fed rats it was 77.9% of the respective controls. Theobromine produced significant decreases in thymus weights, with caffeine producing smaller decreases. The theobromine-fed rats showed severe testicular atrophy with extensive spermatogenic cell degeneration and necrosis, while the testes of rats fed caffeine for 7 or 8 wk showed only scattered vacuolar degeneration of spermatogenic cells. Caffeine appears to be more potent than theobromine as an anorexic agent in rats, but to be equivalent to theobromine in its potential for inducing thymic atrophy and spermatogenic cell destruction with testicular atrophy.     

Reproductive toxicity associated with acrylamide treatment in male and female rats

The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fetal outcomes were evaluated. Females received ACR (25, 50, 100 ppm) for 2 wk prior to initiation of breeding and then throughout gestation and lactation. Hindlimb splaying was apparent in the 200-ppm males by wk 4; less severe splaying appeared in the 100-ppm group at wk 8. Disruptions in copulatory behavior preceded the appearance of this ataxia. These disruptions in mating performance interfered with ejaculatory processes and subsequent transport of sperm, since semen was found in the uterus of only 1 of the 15 females mated with the 100-ppm males at wk 9. Moreover, only 33% of the females mated (wk 10) to the 100-ppm males were pregnant. Postimplantation loss was also significantly increased in this group. Hindlimb splaying appeared in the females receiving 100 ppm ACR during wk 1-2 of pregnancy. Body weight and fluid intake were also depressed. Dams in the 50-ppm group showed depression in these parameters during the last 2 wk of lactation. ACR did not significantly affect mating performance of the females, pregnancy rates, litter size, or survival. However, ACR did significantly depress pup body weight at birth (100-ppm group) and weight gain during lactation through post-weaning, d 42 (50- and 100-ppm groups). Vaginal patency was delayed in the 100-ppm group only.     

Comparative study of 8-monohydromirex and mirex toxicity in male rats

Male rats were fed 0, 0.5, 5.0, 50, and 75 ppm mirex or 8-monohydromirex for 28 days. There were no consistent differences between weight gain of treated or control groups. There were significant increases in LW/BW in the 5, 50, and 75 ppm mirex and 8-monohydromirex treatment groups. Serum β-glucuronidase was elevated in the 0.5, 50, and 75 ppm mirex treated groups, and was elevated in the 5, 50, and 75 ppm 8-monohydromirex treated groups. There were no consistent changes in serum sorbitol dehydrogenase in any treatment group, but there were significant increases in liver sorbitol dehydrogenase at all levels for both toxicants. Hepatic microsomal parameters were induced by both compounds. No consistent toxic effects resulting from mirex or 8-monohydromirex treatment were indicated by serum glucose, protein, and cholesterol or by selected hematological factors. The histological changes observed in the livers of animals treated with mirex and 8-monohydromirex included cell swelling with increased cytoplasmic density; a dense homogenous region centered around the nuclear area; hyaline or myelin-like cytoplasmic inclusions appearing in some tissue sections of the highest treatment levels; and lipidosis. Histological changes in testes of treated rats were less obvious than lesions observed in the liver. There was a loss of staining intensity of the seminiferous tubules associated with hypocellularity of the tubules. Decreased spermatogenesis was evident in three rats from the high dose groups. Both compounds produced detectable histological changes in the thyroid glands at the 75 ppm treatment level. There did not appear to be any consistently significant differences between the toxic effects, either qualitative or quantitative, of mirex and 8-monohydromirex in rats fed either compound for 28 days.     

Evaluation of the subacute nephrotoxicity of cyclohexane and other industrial solvents in the female Sprague-Dawley rat

The subacute nephrotoxicity of more than 20 industrial solvents has been compared in female Sprague-Dawley rats. The animals were given 5 i.p. injections of the solvents per week for 2 weeks at doses ranging from 1/20 to 1/5 of the i.p. or oral LD50 and the urinary excretion of N-acetyl-beta-D-glucosaminidase, beta 2-microglobulin and albumin was determined. Under these experimental conditions, two solvents, cyclohexane and styrene, were found to cause some tubular injury as evidenced by a statistically significant increase of beta 2-microglobulinuria. At the same dose, styrene was more tubulotoxic than cyclohexane but the opposite was observed when the solvents were administered proportionally to their LD50. The increased beta 2-microglobulinuria caused by cyclohexane was both time- and dose-dependent. It was not accompanied by changes in the glomerular filtration rate and the renal plasma flow, but at the highest dose (1.5 g/kg) the renal concentrating ability was depressed. These renal tubular effects can most likely be ascribed to cyclohexanol, the main metabolite of cyclohexane. As cyclohexane is a widely used industrial solvent with a relatively high threshold limit value (TWA-TLV: 300 ppm) it might represent an underestimated risk for the renal function of exposed populations.     

Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aorta ex-vivo

Abstract

Context: Diazinon (DZN) is a widely used organophosphate insecticide. Although mechanism of DZN cardiovascular toxicity is primarily mediated through inhibition of acetylcholinesterase, however, DZN causes remarkable atropine-insensitive hypotension in rats. It has been proved that oxidative stress is an important mechanism of DZN toxicity especially in chronic exposure. Crocin, an active ingredient of saffron, has been found to antagonize the hypotensive effects of DZN in rats, but do not reverse acetylcholinesterase inhibition. Objective: In this study the effects of DZN on contractile and relaxant responses in rat aorta as well as ex-vivo antioxidant actions of crocin have been investigated. Materials and methods: Rats were divided into 7 groups: corn oil (control), DZN (15?mg/kg/day, gavage), crocin (12.5, 25 and 50?mg/kg/day, i.p.) plus DZN, vitamin E (200?IU/kg, i.p., three days a week) plus DZN and crocin (50?mg/kg/day, i.p.) groups. Treatments were continued for 4 weeks. Contractile and relaxant responses were evaluated on the isolated aorta. Results: Our results showed that DZN not only decreased the contractile responses to KCl and Phenylephrine (PE) (p?<?0.001), but also attenuated the relaxant response to acetylcholine (ACh) (p?<?0.01). Crocin and vitamin E attenuated lipid peroxidation, improved the reduction of contractile responses by KCl and PE and restored the decrease in ACh relaxation in rat aorta. Conclusion: DZN induced vascular toxicity which may be due to oxidative stress and not to a cholinergic mechanism. Crocin improved toxic effects of DZN via reducing lipid peroxidation and restoring altered contractile and relaxant responses in rat aorta.     

Comparison of toxicity induced by iodine and iodide in male and female rats

In risk assessments the various forms of iodine have been treated as if they were toxicologically equivalent. While iodide (I-) and iodate (IO3-) have been studied, no studies concerned with the subchronic toxicity of iodine (I2) have been conducted in experimental animals. This study examined toxicities associated with iodine. Rats were treated with 0, 1, 3, 10, and 100 mg/l of either iodine or iodide (as Nal) in the drinking water for 100 d. Treatment had no effect on body, brain, or heart weights in either sex, or on testes weights in male rats. Although differences in kidney and liver weights were noted, they did not appear to be treatment related. Thyroid weight in male rats was significantly increased with an increasing concentration of iodide in the water, but not iodine. In contrast, thyroid weight decreased at the highest dose of iodide in female rats. Hematocrit, hemoglobin, and blood urea nitrogen (BUN) values were relatively constant and did not vary with treatment. There were no significant differences in AST, ALT, cholesterol, and triglyceride values. After 10 d on treatment a dose-related trend in increased plasma T4 concentrations was observed in both sexes treated with iodine. Statistically significant increases in the T4/T3 ratio in both sexes was also noted with iodine treatment. This increase was maintained for 100 d of treatment. Iodide did not produce this effect at 10 d. Although there was a significant increase in T4/T3 ratios in female rats after 100 d of treatment with iodide, the magnitude of the changes was smaller than that observed with iodine treatments. The results of this study indicate that iodine and iodide affect thyroid hormone status in substantially different ways.     

羟基脲对雄性大鼠的生殖毒性

目的观察羟基脲(HU)对雄性大鼠的生殖毒性。方法雄性大鼠分别腹腔注射HU×100、200和400mg·kg-1,连续10d。末次给药后分别于d9、d23处死动物。结果停药d9时,200、400mg·kg-1组不活动精子增加明显(P<0.05或P<0.01);停药d23时,各给药组睾丸脏/体比都明显下降(P<0.05或P<0.01);400mg·kg-1组附睾脏/体比下降明显(P<0.05),并且仍然有大量不活动精子(P<0.01);200、400mg·kg-1组精子计数明显减少(P<0.01);随给药浓度增加,各组精子畸形数量增加(P<0.01)。结论雄性大鼠连续10d腹腔注射羟基脲100mg·kg-1以上,对生殖系统产生明显毒性。