Pancreatic Hepatocytes Associated with Chronic 2,6-Dichloro-p-Phenylenediamine Administration in Fischer 344 Rats

1989 ◽  
Vol 17 (1_part_1) ◽  
pp. 1-6 ◽  
Author(s):  
Margarita M. McDonald ◽  
Gary A. Boorman

Pancreatic tissue (original and recut sections) from Fischer 344 rats fed 2,6-dichloro-p-phenylenediamine in a chronic (2-year) carcinogenesis bioassay was evaluated for presence of pancreatic hepatocytes (PH) by light microscopy. PH were found in dose groups as follows: males–0 ppm (controls)–0/50 (0%), 1,000 ppm–4/50 (8%), 2,000 ppm–9/50 (18%); females-0 ppm (controls)–1/50 (2%), 2,000 ppm–15/50 (30%), 6,000 ppm–15/49 (31%). This represented a significant dose-related increased incidence of PH in 2,000-ppm males, and 2,000- and 6,000-ppm females. A statistically significant increase ( p < 0.01) in pancreatic acinar atrophy and fibrosis was also seen in treated female rats, but the relationship of these lesions to the PH is unclear.

1979 ◽  
Vol 10 (2-3) ◽  
pp. 130-142 ◽  
Author(s):  
J.R. Ducharme ◽  
A.M. Morera ◽  
P. Laurin ◽  
R. Collu ◽  
L. Audi ◽  
...  

2004 ◽  
Vol 32 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Gary W. Trimmer ◽  
James J. Freeman ◽  
R. A. J. Priston ◽  
Jan Urbanus

Two-year dietary studies were conducted to determine the chronic toxicity and its reversibility, and the carcinogenicity of P70(H) and P100(H) white mineral oils in Fischer-344 rats (F-344). The studies were identical in design and followed the Organization for Economic Cooperation and Development, Guidelines for Testing Chemicals, Guideline 453, 1981. Additional endpoints evaluated were: (1) extent of mineral hydrocarbon deposition in liver, kidneys, mesenteric lymph nodes, and spleen of female rats at 3, 6, 12, 18 and 24 months, and (2) reversibility of effects following cessation of exposure. Dietary concentration were 60, 120, 240, and 1, 200 mg/kg/day, adjusted periodically to account for bodyweight changes. Study results were consistent with preceding subchronic studies. No treatment-related mortality, neoplastic lesions, or changes in clinical health, hematology, serum chemistry, or urine chemistry were evident in any group administered either white oil. Statistically significant higher food consumption was noted in the 1, 200 mg/kg group males and females exposed to either white oil and statistically significant higher body weights were noted in the 1, 200-mg/kg males during the latter portion of the P100(H) study. Higher mesenteric lymph node weights were accompanied by increased severity of infiltrating histiocytes. This occurred to a greater extent with the P70(H) than the P100(H) oil. No other histopathology of significance was observed. Mineral hydrocarbons were detected in the liver following exposure to either oil. Maximal concentrations of mineral hydrocarbons in the liver were similar with both oils but occurred more rapidly with the P70(H) oil. Liver mineral hydrocarbon content returned to near-background levels during the reversibility phase. In conclusion, lifetime exposer of F344 rats to P70(H) and P100(H) white oils resulted in only minimal findings and with no consequence to clinical health. Thus, under the conditions of these studies, the No Observable Adverse Effect Level (NOAEL) for these studies was considered to be 1, 200 mg/kg/day.


1995 ◽  
Vol 14 (8) ◽  
pp. 662-671 ◽  
Author(s):  
RH Garman ◽  
DE Dodd ◽  
B. Ballantyne

1 Male and female Fischer 344 rats were exposed to 2,4- pentanedione (2,4-PD) vapour acutely (4 h) at 1265 or 1811 ppm, or for 6 h day-1 , 5 days a week for 14 weeks to 0, 101, 307 or 650 ppm. 2 Mortality occurred during or within a few hours of the acute exposures (10% at 1265 ppm; 70% at 1811 ppm). No animal had gross or microscopic brain lesions. 3 All female rats (20) and 10 of 30 male rats exposed to 650 ppm 2,4-PD vapour died by the 38th study day (29 exposures); there were no subsequent male deaths. Twenty-five of the 30 animals that died, and seven of the 15 males that survived, had light microscopical evidence of degenerative lesions, principally within the caudate/putamen nuclei, nuclei of the cerebellar medulla, and vestibular nuclei. Less frequently involved, in animals that died, were various regions of the cerebral cortex. The early histopathological lesions, seen from the 16th study day (12 exposures) to the 38th study day (28 exposures) were characterised by malacia. When present, lesions in male rats surviving the 14-weeks of 650 ppm 2, 4-PD expo sure were characterised by malacia and gliosis. No peripheral nerve lesions were seen by light or transmis sion electron microscopy. 4 Neither mortality nor neuropathology were seen in rats subchronically exposed to 101 or 307 ppm, 2,4-PD vapour.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 53-53
Author(s):  
Ming-Tsang Wu

53 Background: Arecoline is the major alkaloid of areca nut which is one major risk of developing esophageal squamous cell carcinoma (ESCC) in the Asian population. This study aims to establish one rat model to study the relationship of areca nut exposure with the development of ESCC. Methods: Six-week-old Fischer 344 male rats were injected subcutaneously with 0.5 mg/kg NMBA thrice a week for the first 5 weeks and given water without or with arecoline (500 mg/ml) for 30 weeks. Results: With co-treatment of arecoline, NMBA-injected rats had significantly more esophageal papillomas (p = 0.02) and marginally significantly more tongue papillomas (p= 0.09) per rat, compared to those with NMBA only in the end of week 30. No papilloma was found in the lung, liver and/or stomach among all experimental groups. The histological features of esophageal papilloma showed the hyperplastic changes of squamous epithelium. Conclusions: This established animal model can be ideally used to study areca nut-associated esophageal carcinogenesis.


1968 ◽  
Vol 22 (2) ◽  
pp. 547-554 ◽  
Author(s):  
Jan W. Kakolewski ◽  
Verne C. Cox ◽  
Elliot S. Valenstein

Data are presented to demonstrate that the effects of gonadectomy on body weight and food consumption differ in male and female rats. The findings are related to the authors' report of sex differences in the effects of ventromedial hypothalamic damage. A review of the literature on the relationship of the gonads to body weight in different species is presented.


2002 ◽  
Vol 21 (1) ◽  
pp. 39-53 ◽  
Author(s):  
Leigh Ann Burns-Naas ◽  
Robert G. Meeks ◽  
Gary B. Kolesar ◽  
Richard W. Mast ◽  
Michael R. Elwell ◽  
...  

Octamethylcyclotetrasiloxane (D4) is a low-molecular-weight cyclic siloxane used primarily in the synthesis of silicone polymers. The objective of the present study was to evaluate the subchronic toxicity of D4 following a 3-month nose-only inhalation exposure. Male and female Fischer 344 rats (20/sex/group) were exposed 6 h/day, 5 days/week for 3 months to vapor concentrations of 0, 35, 122, 488, and 898 ppm D4. Also, an additional 10 per sex in the control and high-exposure groups were allowed a 4-week recovery period to observe reversibility, persistence, or delayed occurrence of any potential adverse effects. Body weights and food consumption were monitored at least twice weekly over the course of exposures. Approximately 18 hours preceding euthanasia, animals were transferred into metabolism cages for urine collection, and were fasted. At necropsy, rats were anesthetized with pentobarbital and euthanized by exsanguination. Blood was collected for hematological and clinical biochemical analyses. Selected organ weights were measured and a complete set of tissues was taken for histopathological examination. A concentration-dependent increase in absolute and relative liver weight (488 to 898 ppm) and a significant decrease in ovarian weight (898 ppm) were observed in female rats. Exposure to D4 via nose-only inhalation (35 to 898 ppm) produced minor alterations in hematological and serum chemistry parameters that were considered either incidental and of little toxicological significance (hematology) or suggestive of metabolic adaptation/alteration (serum chemistry) in response to exposure-related hepatomegaly. There were no histopathological findings noted in the liver. Histopathological evidence indicated the primary target organs following D4 inhalation exposure to be components of the female reproductive tract. Reversible histopathological changes were observed in the ovary (hypoactivity) and vagina (mucification) of female rats in the high-dose group only (898 ppm). Although an increase in the incidence and severity of both macrophage accumulation, interstitial inflammation, and eosinophil infiltration was observed in the lungs of male and female rats exposed to D4, the toxicological significance is uncertain as other inhalation studies at similar concentrations failed to show these effects. In summary, nose-only inhalation of a high concentration of D4 resulted in reversible histopathological changes in the female rat reproductive tract. Lower concentrations did not elicit these same effects.


1996 ◽  
Vol 270 (2) ◽  
pp. R413-R419 ◽  
Author(s):  
A. Laviano ◽  
M. M. Meguid ◽  
J. R. Gleason ◽  
Z. J. Yang ◽  
T. Renvyle

We studied the effect of gender on food intake, meal number, and meal size in eight 10-wk-old female and seven age-matched male Fischer 344 rats for 44 consecutive days. Although food intake (g/100 g body wt) was similar in males and females (5.42 +/- 0.10 vs. 5.13 +/- 0.13 g food.day-1.100 g body wt-1, respectively; not significant), weight gain in males was approximately seven times greater than in female rats (1.49 +/- 0.07 vs. 0.21 +/- 0.03 g/day, respectively; P < 0.001). During this time, males had a relatively constant food intake. They increased their meal size but decreased their meal number. In female rats, food intake was relatively stable for the duration of the study, despite cyclically and reciprocally recurring changes in meal number and meal size, which are synchronized with the estrous cycle. Data confirm that net food intake is a dynamic process and suggest that, in the rat, the homeostasis of food intake in response to external as well as internal stimuli is maintained via the modulation of meal number and size.


Author(s):  
D.R. Mattie ◽  
J.J. Maslanka ◽  
C.D. Flemming

Halocarbon 27-S (H 27-S) is a polymer of chlorotrifluoroethylene (CTFE). Since metabolism of CTFE yields inorganic fluoride, it was believed that H 27-S would also yield fluoride in the blood. Exposure to fluorine results in deposition in bone as calcium fluoride or fluorapatite. Deposition of fluoride in the bone matrix should result in an altered calcium phosphorus ratio (CaP). The objective of this study was to determine the CaP of femurs of male and female rats exposed subchronically to H 27-S using energy dispersive x-ray analysis techniques and to compare CaP from exposed rats with the CaP of control rats.Male and female rats were dosed daily with 2.5 g H 27-S/kg body weight by gavage for 7 or 21 days. Rats were sacrificed at 7, 21 and 35 days (14 days after the 21 day dosing). Femurs of three rats of each sex and each group were analyzed.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1085
Author(s):  
Héctor Palacios-Jordan ◽  
Miguel Z. Martín-González ◽  
Manuel Suárez ◽  
Gerard Aragonès ◽  
Begoña Muguerza ◽  
...  

Circadian rhythms are ~24 h fluctuations of different biological processes that are regulated by the circadian clock system. They exert a major influence on most of the metabolism, such as the hepatic metabolism. This rhythmicity can be disrupted by obesogenic diets, fact that is considered to be a risk factor for the development of metabolic diseases. Nevertheless, obesogenic diets do not affect both genders in the same manner. We hypothesized that the circadian rhythms disruption of the hepatic metabolism, caused by obesogenic diets, is gender-dependent. Male and female Fischer 344 rats were fed either a standard diet or a cafeteria diet and sacrificed at two different moments, at zeitgeber 3 and 15. Only female rats maintained the circadian variations of the hepatic metabolism under a cafeteria diet. Most of those metabolites were related with the very low density lipoprotein (VLDL) synthesis, such as choline, betaine or phosphatidylcholine. Most of these metabolites were found to be increased at the beginning of the dark period. On the other hand, male animals did not show these time differences. These findings suggest that females might be more protected against the circadian disruption of the hepatic metabolism caused by a cafeteria diet through the increase of the VLDL synthesis at the beginning of the feeding time.


1998 ◽  
Vol 17 (4) ◽  
pp. 393-411 ◽  
Author(s):  
Tirumuru V. Reddy ◽  
Greg R. Olson ◽  
Barry Wiechman ◽  
Gunda Reddy ◽  
Joni Torsella ◽  
...  

The subchronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 rats was evaluated by feeding a powdered certified laboratory diet containing 0, 66.7, 400 and 800 mg TNBl kg diet for 90 days. The calculated average TNB intake was 4.29, 24.70, and 49.28 mg/kg body weight (BW)day for females and 3.91, 22.73, and 44.16 mg/ kg BWI day for males. Food intake in the 400 and 800 mg/kg diet dose groups of both sexes was decreased throughout the study and resulted in a significant decrease in absolute body weights. A significant decrease in relative testicular weights and a significant increase in the relative liver weight were observed in male rats receiving 400 or 800 mg TNB/kg diet. A significant increase in the relative spleen weights of both sexes receiving 400 or 800 mg TNB diet was noted. The relative liver weight was also increased only in female rats maintained on the 800 mg TNB diet. Histopathological examinations revealed that the susceptible organs for TNB toxicity were kidney (hyaline droplets) in all male dose groups and testes (seminiferous tubular degeneration) in rats receiving 400 and 800 mg TNB diet groups. The spleen was also affected (extramedullary hematopoiesis) in both sexes in the 400 and 800 mg dose groups. Hematological studies at both 45 (data not given) and 90 days in the 400 and 800 mg dose groups indicated decreased values for red blood cell counts and hemoglobin content, while reticulocytes and methemoglobin levels were increased. Clinical chemistry parameters were unaffected. Based on kidney toxicity and hematological effects, a Low Observed Adverse Effect Level (LOAEL) of 3.91 mg/kg BWI day was suggested for subchronic toxicity studies on TNB.


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