scholarly journals Chronic Inhalation Exposure of Rats for up to 104 Weeks to a Non–Carbon-Based Magnetite Photocopying Toner

2008 ◽  
Vol 27 (6) ◽  
pp. 427-439 ◽  
Author(s):  
Ronald S. Slesinski ◽  
Duncan Turnbull
Keyword(s):  
Lymph Nodes ◽  
Inhalation Exposure ◽  
Clinical Pathology ◽  
Acrylic Resin ◽  
Lymphocytic Infiltration ◽  
Female Rats ◽  
Whole Body ◽  
Male And Female ◽  
Male And Female Rats ◽  
Carbon Based

Male and female Han Wistar rats were exposed for 6 h/day, 5 days/week for 13 or 104 weeks (whole body) to a magnetite photocopying toner. The toner contained 45% to 50% magnetite, with 45% to 50% styrene acrylic resin and less than 5% external additives, including hydrophobic amorphous silica and proprietary surface functional modifiers. Exposure levels were 1, 5, and 25 mg/m3 for the 13-week study and 1, 4, and 16 mg/m3 for the 104-week study. Lung toner burdens averaged 36, 288, and 604 μg per lung after 104 weeks’ exposure at 1, 4, and 16 mg/m3. The lung burdens were lower than have been reported in a similar study with a carbon-based toner. There were no significant effects on weight gain or food consumption in either study, or on clinical pathology parameters examined in the 13-week study. After 104 weeks’ exposure at 16 mg/m3, macroscopic examination revealed dark discoloration of the lungs and associated lymph nodes. Lung weights were significantly elevated by 21% and 14% for male and female rats, respectively. Microscopic findings indicative of a mild inflammatory response were similar in both studies, and included the presence of black-pigmented macrophages in the lungs and tracheobronchial and mediastinal lymph nodes; increased incidences of perivascular/peribronchiolar inflammatory cell infiltration; inflammation of the alveolar ducts (characterized by aggregations of black-pigmented alveolar macrophages and interstitial lymphocytic infiltration); increased cellularity of the bronchiole-associated lymphoid tissue; and a few instances of alveolar ciliated metaplasia. The 104-week study showed no increase in the incidence of pulmonary tumors.

scholarly journals Electron microscopic changes of lymph nodes during correction of sodium glutamate action by melatonin

2020 ◽  
Vol 26 (1) ◽  
pp. 59-64 ◽  
Author(s):  
T.V. Harapko
Keyword(s):  
Lymph Nodes ◽  
Monosodium Glutamate ◽  
Reproductive Age ◽  
Female Rats ◽  
Mesenteric Lymph Nodes ◽  
Electron Microscopic ◽  
Male And Female ◽  
White Rats ◽  
Mesenteric Lymph ◽  
Male And Female Rats

The effect of monosodium glutamate on lymphoid organs remains insufficiently studied. Also, no less relevant is the issue of correction of changes caused by the action of monosodium glutamate. The aim of the study was to study the electron microscopic changes in the parenchyma of the lymph nodes of rats under the action of monosodium glutamate for six weeks and during correction with melatonin. The experimental study was performed on 66 white male and female rats of reproductive age. The structure of mesenteric lymph nodes of white rats under the conditions of physiological norm at the electron microscopic level was studied in 10 intact animals. Experimental animals were divided into 4 groups, each with 10 animals. The control was 16 white rats, which instead of a high-calorie diet (HCD) received a standard diet of vivarium. HCD was achieved by adding to the diet of monosodium glutamate at a dose of 0.07 g/kg body weight of rats. The dose of melatonin was 10 mg/kg body weight of rats, administered orally daily at the same time in the afternoon. The electron microscopic structure of the mesenteric lymph nodes of male and female rats of reproductive age of the intact and control groups corresponds to the species norm. The study showed that monosodium glutamate causes changes in the parenchyma of the lymph nodes as in alimentary obesity. After six weeks of HCD, the number of apoptically altered lymphocytes increases. That part of lymphocytes, which has no signs of karyorrhexis or karyolysis, has a karyolemma with deep intussusception, the cytoplasm is enlightened, the tubules of the granular endoplasmic reticulum in cells with signs of edema, dilated, mitochondrial ridges swollen, damaged. There are profound destructive changes in the cellular composition of the organ and violations at the level of all parts of the vascular bed. After six weeks of melatonin correction, the number of macrophages and plasma cells decreased, in some lymphocytes the nucleolus is not clearly expressed, the karyolemma is uneven, the cytoplasm is enlightened, the number of osmophilic (fatty) inclusions decreases both in the intercellular space and in the cytoplasm of the cell. Therefore, the introduction of melatonin led to a significant restoration of the structural organization, and hence the function of this organ.

Comparative pulmonary toxicity of inhaled metalworking fluids in rats and mice

2016 ◽  
Vol 33 (5) ◽  
pp. 385-405 ◽  
Author(s):  
Kristen R Ryan ◽  
Mark F Cesta ◽  
Ronald Herbert ◽  
Amy Brix ◽  
Michelle Cora ◽  
...  
Keyword(s):  
Animal Studies ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Metalworking Fluids ◽  
Whole Body ◽  
Chemical Components ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rats And Mice

Metalworking fluids (MWFs) are complex formulations designed for effective lubricating, cooling, and cleaning tools and parts during machining operations. Adverse health effects such as respiratory symptoms, dermatitis, and cancer have been reported in workers exposed to MWFs. Several constituents of MWFs have been implicated in toxicity and have been removed from the formulations over the years. However, animal studies with newer MWFs demonstrate that they continue to pose a health risk. This investigation examines the hypothesis that unrecognized health hazards exist in currently marketed MWF formulations that are presumed to be safe based on hazard assessments of individual ingredients. In vivo 13-week inhalation studies were designed to characterize and compare the potential toxicity of four MWFs: Trim VX, Cimstar 3800, Trim SC210, and Syntilo 1023. Male and female Wistar Han rats or Fischer 344N/Tac rats and B6C3F1/N mice were exposed to MWFs via whole-body inhalation at concentrations of 0, 25, 50, 100, 200, or 400 mg/m3 for 13 weeks, after which, survival, body and organ weights, hematology and clinical chemistry, histopathology, and genotoxicity were assessed following exposure. Although high concentrations were used, survival was not affected and toxicity was primarily within the respiratory tract of male and female rats and mice. Minor variances in toxicity were attributed to differences among species as well as in the chemical components of each MWF. Pulmonary fibrosis was present only in rats and mice exposed to Trim VX. These data confirm that newer MWFs have the potential to cause respiratory toxicity in workers who are repeatedly exposed via inhalation.

Effects of a 13-Week Chloropentafluorobenzene Inhalation Exposure of Fischer 344 Rats and B6C3F1 Mice

1991 ◽  
Vol 7 (4) ◽  
pp. 309-318 ◽  
Author(s):  
Edwin R. Kinkead ◽  
Susan K. Bunger ◽  
Edgar C. Kimmel ◽  
Carlyle D. Flemming ◽  
Henry G. Wall ◽  
...  
Keyword(s):  
Inhalation Exposure ◽  
Chemical Warfare Agents ◽  
Female Rats ◽  
Laboratory Animals ◽  
High Concentration ◽  
Inhalation Study ◽  
Male And Female ◽  
Male And Female Rats ◽  
Warfare Agents ◽  
Rats And Mice

Chloropentafluorobenzene (CPFB) has been identified as a can didate simulant for nonpersistent chemical warfare agents. Acute toxicity studies have shown that CPFB has limited adverse ef fects on laboratory animals. A 21-day inhalation study of rats and mice to 2.5, 0.8, and 0.25 mg CPFB/liter resulted in re duced weight gain in male and female rats exposed at the high concentration only and identified the liver as a potential target organ. This multiconcentration inhalation study was designed to detect a no-observable-effect level associated with repeated expo sure to CPFB. Male and female rats and mice were exposed to 250, 50, or 10 mg CPFB/m3 (0.25, 0.05, or 0.01 mg CPFB/li ter) for 13 weeks. No treatment-related effects on body weight, clinical chemistries, mortality, absolute or relative organ weight or histopathology were noted.

Inhalation Toxicity and Genotoxicity of Hydrofluorocarbon (HFC)-236fa and HFC-236ea

2000 ◽  
Vol 19 (2) ◽  
pp. 69-83 ◽  
Author(s):  
William J. Brock ◽  
David P. Kelly ◽  
Susan M. Munley ◽  
Karin S. Bentley ◽  
Kathy M. McGown ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Human Lymphocytes ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Seminiferous Tubules ◽  
Inhalation Toxicity ◽  
Male And Female ◽  
Male And Female Rats

The acute, subchronic, and developmental and genetic toxicity of hydrofluorocarbon (HFC)-236fa and HFC-236ea were evaluated to assist in establishing proper handling guidance. In acute inhalation studies, rats were exposed whole body for 4 hours to various concentrations of each isomer. Based on the lack of mortality, the approximate lethal concentration for HFC-236ea for male rats was > 85,000 ppm. For HFC-236fa, the LC50 for males and females (combined) was > 457,000 ppm. Narcotic-like effects, e.g., prostration, incoordination, and reduced motor activity, were observed only during exposure to either isomer, but were not evident after termination of exposure. In cardiac sensitization studies, HFC-236ea induced cardiac sensitization at ≥ 35,000 ppm, with fatal responses occurring at 50,000 ppm and greater. For HFC-236fa, a cardiac sensitization response was observed at 150,000 ppm and greater but not at 100,000 ppm. A fatal cardiac sensitization response was observed in one dog exposed to 150,000 ppm HFC-236fa. In 90-day subchronic inhalation studies, male and female rats were exposed whole body to HFC-236ea at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. Similarly, male and female rats were exposed whole body to HFC-236fa at concentrations of 0, 5000, 20,000, or 50,000 ppm for 6 hours/day, 5 days/week. During exposure, narcotic-like effect (reduced acoustic startle response) was observed at 50,000 ppm with both isomers, although there appeared to be an adaptive response to this effect as the study progressed. With HFC-236ea, dilatation of the seminiferous tubules, without effects on germ or Sertoli cells, was observed only in rats at 50,000 ppm. No other effects on in-life measures or on clinical or anatomic pathology, including histopathology, were observed for either isomer. In rat developmental toxicity studies, no evidence of embryotoxicity or teratogenicity was observed with either isomer exposed up to 50,000 ppm during gestational days 7 to 16. Also, no developmental toxicity was observed in rabbits exposed to HFC-236fa at concentrations of up to 50,000 ppm during gestational days 7 to 19. Neither of the HFC-236 isomers was mutagenic in the Ames reverse mutation assay or clastogenic in the chromosomal aberration assay with human lymphocytes. No increase in chromosomal aberrations was observed in in vivo micronucleus studies with either isomer.

scholarly journals A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

2016 ◽  
Vol 35 (6) ◽  
pp. 683-691 ◽  
Author(s):  
Tennille K. Marx ◽  
Róbert Glávits ◽  
John R. Endres ◽  
Philip A. Palmer ◽  
Amy E. Clewell ◽  
...  
Keyword(s):  
Body Weight ◽  
Animal Studies ◽  
Clinical Pathology ◽  
Morus Alba ◽  
Water Soluble ◽  
Female Rats ◽  
Repeated Dose ◽  
Oral Toxicity ◽  
Male And Female ◽  
Male And Female Rats

Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested.

scholarly journals Dietary cottonseed consumption induced subfertility in male and female rats: a potent eco-friendly rodenticide compound

2021 ◽  
Author(s):  
Fariborz Nowzari ◽  
Farhad Rahmanifar ◽  
Nader Tanideh ◽  
Mohammad Reza Dorvash ◽  
Arezoo Khoradmehr ◽  
...  
Keyword(s):  
Treatment Group ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Control Group ◽  
Cottonseed Flour ◽  
Male And Female ◽  
Treatment Groups ◽  
Male And Female Rats ◽  
Significant Difference

Abstract Effects of cottonseed flour in male and female rats’ fertility based on hormonal and histomorphometry changes were studied. Sixty-four Sprague-Dawley adult male and female rats were randomly divided into control and treatment groups. Treatment group was received diets containing cottonseed flour for 35 days. Control group was given standard rat food. Body and testis weights, epididymis semen evaluation indices and serum sex steroid hormones were determined. Histomorphometry alterations of testes and ovary were evaluated. Then, normal female and male rats were mated by rats in both groups and after 35 days, number of pups was measured. However, there was no significant difference in whole body and testes weights, sperm concentration and viability between the control and treatment groups, respectively. Moreover, sperm motility in the treatment rats was significantly lower than the control group. Serum hormones alterations were not significant, but histomorphometry evaluations of testes showed significant changes in the testis structures after chronic consumption of cottonseed flour. In the female rats, body weight did not have significant difference between the treatment and control groups. Histomorphometry data in female ovary showed significant reduction of primary follicle volume and number in the treatment group against control. Follicle stimulating hormone showed insignificant reduction in the treatment group. Number of pups was significantly reduced in the female rats fed by cottonseed flour. Cottonseed flour in rat diet had adverse effects on rat reproduction. Therefore, it can be used as an efficient product for control of the rat population as a natural rodenticide agent.

Exercise inhibits progressive growth of the Morris hepatoma 7777 in male and female rats

1989 ◽  
Vol 67 (8) ◽  
pp. 864-870 ◽  
Author(s):  
Vickie E. Baracos
Keyword(s):  
Tumour Growth ◽  
Muscle Protein ◽  
Exercise Program ◽  
Female Rats ◽  
Whole Body ◽  
Male And Female ◽  
Male And Female Rats ◽  
Tumour Implantation ◽  
Progressive Growth ◽  
Morris Hepatoma

Male and female rats were either trained to swim for a 6-week period or they remained sedentary. Rats were implanted with Morris hepatoma 7777 after 3 weeks of swimming and were sacrificed after a further 3 weeks. Exercised rats of both sexes showed a significant reduction in tumour weight at sacrifice, compared with sedentary controls (p < 0.01). Similarly, when rats were first implanted with tumours and then placed on an exercise program of 3 weeks duration, tumour growth was also reduced (p < 0.05). These results suggest that the tumour may be sensitive to exercise at more than one point in its development. Tumour growth was inhibited to a similar extent whether the total swimming time was 10, 20, or 30 h over the 3-week period. Although sedentary, tumour-bearing rats were anorexic; both male and female rats showed significant improvement of appetite during the period of tumour growth, in response to exercise. Tumour implantation was associated with significant losses of whole body and muscle protein. The progression of this wasting was not significantly altered by exercise.Key words: Morris hepatoma 7777, cancer, tumour, exercise, skeletal muscle, cachexia, protein.

Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration

2003 ◽  
Vol 23 (6) ◽  
pp. 427-436 ◽  
Author(s):  
Susan C. J. Sumner ◽  
Derek B. Janszen ◽  
Bahman Asgharian ◽  
Timothy A. Moore ◽  
Horace D. Parkinson ◽  
...  
Keyword(s):  
Gender Differences ◽  
Methyl Ether ◽  
Inhalation Exposure ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
And Gender ◽  
Rats And Mice

Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): IV. Assessment of the Repeated-Dose Toxicological Potential of Synthesized L-Valyl-L-prolyl-L-proline in Male and Female Rats and Dogs

2005 ◽  
Vol 24 (4_suppl) ◽  
pp. 25-39 ◽  
Author(s):  
Yasunori Nakamura ◽  
Izuki Bando ◽  
John H. Mennear ◽  
Bruce K. Bernard
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Pathology ◽  
Female Rats ◽  
Male Rats ◽  
Repeated Dose ◽  
High Dose ◽  
Male And Female ◽  
Organ Weights ◽  
Male And Female Rats

The objective of these repeated-dose, 8-week studies was to assess the toxicological potential of a synthetic tripeptide, L-valyl-L-prolyl-L-proline (VPP), when administered to Charles River rats and Beagle dogs. Groups of 20 male and 20 female rats were fed powdered diets containing sufficient VPP to afford daily doses of 0, 2, 8, or 16 mg/kg body weight (BW)/day. Groups of five male and five female dogs were administered 0, 2, 8, or 16 mg/kg BW/day in hard gelatin capsules. Antemortem evaluative parameters for both species included grossly observable clinical signs, body weight and food consumption, clinical pathology (hematology, clinical chemistry, urinalysis), and ophthalmological examinations. Dogs also received electrocardiographic examinations. Postmortem evaluations in both species included complete necropsy, determination of major organ weights, and histopathological examination of specimens from approximately 50 organs and tissues. All rats and dogs survived to the scheduled termination of the studies and neither species exhibited evidence of VPP effects on appetite or body weight gain/maintenance. Ophthalmic examinations revealed occasional lens clouding in rats, but this occurred in all groups and was not attributable to VPP. Some clinical pathology parameters in both species were occasionally altered, but there was no evidence that this was dose-related. Electrocardiographic examinations in dogs revealed no VPP-associated changes. Mid- and high-dose male rats (but not females) had slightly reduced mean pituitary and kidney weight parameters, whereas mid- and high-dose females had slightly increased mean uterus:body weight ratios. There were no microscopic correlates for these minor changes. Ten percent to 20 % of all female rats (but not males) exhibited corticomedullary mineralization of the kidney and gliosis of the optic nerve, and 10% to 20% of males (but not females) had thymic hemorrhage. Postmortem evaluations of dogs revealed no VPP-related effects on organ weights or either macro- or microscopic appearances of organs. The results of these studies provided no evidence of either local or systemic toxicity. Similarly, there was no evidence of neurotoxicity that might have been detected by the appearance of physical or behavioral changes during gross observations of animals. Although these results do not identify target organs for VPP toxicity, the no-observable-effect level and maximally tolerated dose are both greater than 16 mg/kg/day when administered to male and female rats and dogs for 8 consecutive weeks. Based upon food enhancement levels of VPP currently being evaluated, the resultant margin of safety (160) is substantial.

scholarly journals Inhalation of Talc Induces Infiltration of Macrophages and Upregulation of Manganese Superoxide Dismutase in Rats

2015 ◽  
Vol 34 (6) ◽  
pp. 491-499 ◽  
Author(s):  
Ilseob Shim ◽  
Hyun-mi Kim ◽  
Sangyoung Yang ◽  
Min Choi ◽  
Gyun-baek Seo ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Damage ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
Whole Body ◽  
Inhalation Toxicity ◽  
Inhalation Study ◽  
Male And Female ◽  
Male And Female Rats

Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m3 for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m3 of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m3 talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.

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