Subchronic Hepatotoxicity Evaluation of Hydrazobenzene in Fischer 344 Rats

2012 ◽  
Vol 31 (6) ◽  
pp. 564-571 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Henry G. Wall ◽  
Russell S. Thomas
Keyword(s):  
Body Weight ◽  
Serum Alkaline Phosphatase ◽  
Clinical Signs ◽  
Liver Weight ◽  
Fischer 344 ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Body Weights ◽  
Effect Level ◽  
F344 Rats

Male F344 rats were exposed to hydrazobenzene (HZB) by dietary feed at concentrations of 0, 5, 20, 80, 200, or 300 ppm for 5 days, 2 weeks, 4 weeks, or 13 weeks duration. End points evaluated included clinical observations, body weights, liver weights, serum chemistry, blood HZB, gross pathology, and liver histopathology. There were no HZB exposure-related clinical signs of toxicity. During study weeks 8 through 13, body weight means in rats of the 300 ppm group were 6% lower compared to control rat means. Serum alkaline phosphatase concentrations were decreased in rats of the 300 ppm group at all time points. Relative (to body weight) liver weight increases were observed in rats of the 200 and 300 ppm groups following 5 days (300 ppm only), 2 weeks, 4 weeks, and 13 weeks of exposure. Following 13 weeks of exposure, microscopic findings in the liver were observed only in rats of the 200 and 300 ppm groups and consisted of hypertrophy, macrovesiculation, eosinophilic granular cytoplasm, and bile duct duplication. Blood HZB concentrations ranged from 0.002 to 0.006 µg/mL in rats of the 200 or 300 ppm groups. A no observed effect level of 80 ppm (4.80 mg/kg per d) was selected based on the observation of microscopic hepatocyte alterations at ≥200 ppm HZB.

Subchronic Toxicity Evaluation of Anthraquinone in Fischer 344 Rats

2013 ◽  
Vol 32 (5) ◽  
pp. 358-367
Author(s):  
Darol E. Dodd ◽  
Debra K. Layko ◽  
Katherine E. Cantwell ◽  
Gabrielle A. Willson ◽  
Russell S. Thomas
Keyword(s):  
Body Weight ◽  
Liver Weight ◽  
Fischer 344 ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Serum Aspartate Aminotransferase ◽  
Effect Level ◽  
F344 Rats

Female F344 rats were exposed to anthraquinone (AQ) by dietary feed at concentrations of 0, 50, 150, 469, 938, 1875, or 3750 ppm for 2 or 13 weeks. End points evaluated included clinical observations, body weights, serum chemistry, blood AQ, gross pathology, organ weights, and select tissue histopathology. Mean body weight and food consumption were 5% to 10% lower than control values in rats of the ≥938 ppm group during study weeks 2 through 13. Occasional decreases in body weight means were also observed in rats of the 150 and 469 ppm groups. Increases in liver, kidney, and spleen weights were observed in rats exposed to AQ diet concentrations ≥150 ppm for 13 weeks. Urinary bladder weights were increased at ≥469 ppm. Liver and spleen weights were also increased following 2 weeks of exposure. Liver weight increases were clearly dependent on AQ concentration. At 2 weeks, decreases in serum aspartate aminotransferase (AST), blood urea nitrogen, and creatinine concentrations were observed in higher AQ exposure groups, and AST was decreased at 13 weeks (≥1875 ppm). Microscopic alterations were observed in the liver (mild centrilobular hypertrophy), spleen (mild hematopoietic cell proliferation and pigmentation), and kidneys (minimal hyaline droplets) of rats exposed to AQ for 13 weeks. Blood AQ concentrations ranged from 0.75 to 14.8 µg/mL in rats of the 150 to 3750 ppm groups, respectively, and were similar in value following either 2 weeks or 13 weeks of exposure. A no observed adverse effect level of 469 ppm AQ (31.3 mg/kg/d) was selected based on the absence of liver histopathology.

scholarly journals Subchronic Hepatotoxicity Evaluation of 2,3,4,6-Tetrachlorophenol in Sprague Dawley Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Deborah A. Banas ◽  
Russell S. Thomas
Keyword(s):  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Serum Chemistry ◽  
Sprague Dawley ◽  
Liver Histopathology ◽  
Clinical Observations ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Body Weights

Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12–22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ≥25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 μg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25 mg/kg/day.

Subchronic Hepatotoxicity Evaluation of 1,2,4-Tribromobenzene in Sprague-Dawley Rats

2012 ◽  
Vol 31 (3) ◽  
pp. 250-256 ◽  
Author(s):  
Darol E. Dodd ◽  
Linda J. Pluta ◽  
Mark A. Sochaski ◽  
Kathleen A. Funk ◽  
Russell S. Thomas
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Exposure Time ◽  
Clinical Signs ◽  
Liver Weight ◽  
Sprague Dawley ◽  
Significant Incidence ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level

Male Sprague-Dawley rats were exposed to 1,2,4-tribromobenzene (TBB) by gavage for 5 days, 2, 4, and 13 weeks at 0, 2.5, 5, 10, 25, or 75 mg/kg per d. There were no TBB exposure-related clinical signs of toxicity or changes in body weight. Liver weight increases were dose and exposure time related and statistically significant at ≥10 mg/kg per d. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were dose and time related. The 75 mg/kg per d group had minimally increased mitoses within hepatocytes (5 days only). Hepatocyte vacuolation was observed (13 weeks) and was considered TBB exposure related at ≥25 mg/kg per d. Concentrations of blood TBB increased linearly with dose and at 13 weeks, ranged from 0.5 to 17 µg/mL (2.5-75 mg/kg per d). In conclusion, rats administered TBB doses of 10-75 mg/kg per d for 13 weeks had mild liver effects. A no observed adverse effect level of 5 mg/kg per d was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥10 mg/kg per d.

Lack of Trigeminal Nerve Toxicity in Rats Exposed to Trichloroethylene Vapor for 13 Weeks

2006 ◽  
Vol 25 (6) ◽  
pp. 531-540 ◽  
Author(s):  
Ralph R. Albee ◽  
Pamela J. Spencer ◽  
Keith A. Johnson ◽  
Greg J. Bradley ◽  
Brian R. Marable ◽  
...  
Keyword(s):  
Trigeminal Nerve ◽  
Auditory Brainstem ◽  
Female Rats ◽  
Male Rats ◽  
Fischer 344 ◽  
Clinical Observations ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Brainstem Response ◽  
Effect Level

Male and female Fischer-344 rats were exposed to 1,1,2-trichloroethylene (TCE) at 250, 800, or 2500 ppm for 6 h/day, 5 days/week, for 13 weeks. Weekly body weights and daily clinical observations were recorded and a functional observational battery (FOB) was performed monthly. Postexposure neurotoxicological evaluations included an electrodiagnostic evaluation of auditory function, the trigeminal nerve, and a comprehensive neuropathological examination. After 8 weeks of exposure, female, but not male, rats exposed to 2500 ppm were slightly more reactive to handling than the controls but not after 13 weeks of exposure. After 13 weeks, female rats exposed to 2500 ppm TCE were slightly more active during the 1-min observation period than the controls. There were no treatment-related differences in grip performance, landing foot splay, or on the trigeminal nerve–evoked potential at any dose. At 2500 ppm TCE, mild frequency-specific hearing deficits were observed, including elevated tone-pip auditory brainstem response thresholds. Focal loss of hair cells in the upper basal turn of the cochlea was observed in 2500 ppm–exposed rats. Except for the cochleas of 2500 ppm–exposed rats, no treatment-related lesions were noted during the neuro-histopathologic examination. The no-observable-adverse-effect level for this study was 800 ppm based on ototoxicity at 2500 ppm.

Developmental Toxicity Studies of Triethylene Glycol Monomethyl Ether Administered Orally to Rats and Rabbits

1996 ◽  
Vol 15 (5) ◽  
pp. 349-370 ◽  
Author(s):  
A. M. Hoberman ◽  
W. J. Krasavage ◽  
M. S. Christian ◽  
C. R. Stack
Keyword(s):  
Developmental Toxicity ◽  
Clinical Signs ◽  
Triethylene Glycol ◽  
Monomethyl Ether ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Maternal Body ◽  
Body Weights ◽  
Effect Level ◽  
Dose Levels

Triethylene glycol monomethyl ether (TGME) was administered orally via gavage stomach tube to mated Caesarean delivered (CD) rats and artificially inseminated New Zealand white rabbits on days 6–15 and 6–18 of gestation, respectively, at dose levels of 0, 625, 1,250, 2,500, or 5,000 mg/kg/day (rats) and 0, 250, 500, 1,000, or 1,500 mg/kg/day (rabbits). Clinical signs, maternal body weights, and feed consumption were monitored throughout the treatment period. The surviving rats and rabbits underwent Caesarean section on day 20 and day 29 of gestation, respectively. Fetuses were weighed, sexed, and examined externally and for soft tissue and skeletal alterations. In rats, the high dose significantly reduced maternal body weights, feed consumption, and gravid uterine weights. One dam in this group died on day 13 of gestation. Treatment-related clinical signs were seen only at the highest dose tested. Maternal feed consumption was significantly reduced at 5,000 and 2,500 mg/kg and slightly, but not significantly, reduced at 1,250 mg/kg. Doses as high as 5,000 mg/kg/day did not affect pregnancy rate, implantations, corpora lutea, live fetuses, or fetal sex ratios. Resorptions were significantly increased at 5,000 mg/kg, and fetal body weights were slightly reduced at 1,250 mg/kg and significantly reduced at 2,500 and 5,000 mg/kg. The incidences of malformations and external or internal soft tissue variations were not increased at doses as high as 5,000 mg/kg. Incidences of skeletal variations were increased at doses of 1,250 mg/kg and higher. The no-observable-effect level (NOEL) in rats, for both maternal and developmental toxicity, was 625 mg/kg, while 1,250 mg/kg was a no-observable-adverse-effect level (NOAEL) for maternal toxicity and may be very near the NOAEL for developmental toxicity. In rabbits, 1,500 mg/kg/day reduced maternal body weights and feed consumption and caused death, abortions, treatment-related clinical signs of toxicity, and reduced gravid uterine weights. One doe in the 1,000 mg/kg group died on day 18 of gestation, but no treatment-related signs were seen in the other animals in this group. Doses as high as 1,500 mg/kg did not significantly affect pregnancy rate, implantations, corpora lutea, resorptions, live fetuses, fetal body weights, or sex ratio. Incidences of malformations or external and internal variations were not increased at any of the dose levels. The only developmental toxicity seen in the rabbit was an increase in the incidence of two common skeletal variations, angulated hyoid alae and delayed ossification of the xiphoid process, at the highest dose tested. For maternal toxicity, the NOEL and NOAEL were 250 mg/kg and 500 mg/kg, respectively, and for developmental toxicity the NOEL and NOAEL were 1,000 mg/kg and 1,500 mg/kg, respectively. These studies indicate that TGME was not selectively toxic to developing rat or rabbit conceptuses.

Prenatal Oral (Gavage) Developmental Toxicity Study of Decabromodiphenyl Oxide in Rats

2002 ◽  
Vol 21 (2) ◽  
pp. 83-91 ◽  
Author(s):  
M. L. Hardy ◽  
R. Schroeder ◽  
J. Biesemeier ◽  
O. Manor
Keyword(s):  
Body Weight ◽  
Flame Retardant ◽  
Corn Oil ◽  
Body Weight Gain ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Wide Range ◽  
Effect Level ◽  
Effect Of Treatment

Decabromodiphenyl oxide (DBDPO) is a highly effective flame retardant that is primarily used in electrical and electronic equipment with a secondary, but important, application in upholstery textiles. DBDPO, the second largest volume brominated flame retardant in use today, has undergone a wide range of toxicology tests in mammalian species with the results indicating a no-adverse-effect level of ∼1000 mg/kg/day in oral repeated-dose studies. An oral prenatal developmental toxicity study of the commercial DBDPO product (97% purity) was performed under current EPA OPPTS and OECD guidelines. Female Sprague-Dawley rats (25 mated females/group) received 0, 100, 300 or 1000 mg DBPDO/kg/day via gavage in corn oil during gestation days 0 through 19. All females survived until scheduled sacrifice. No clinical signs of toxicity were observed. Pregnancy rates in the control and treated groups ranged from 96% to 100% and provided 23 or more litters in each group for evaluation on gestation day 20. No effect of treatment was seen in maternal gestational parameters (body weight, body weight gain, and food consumption), uterine implantation data, liver weight, or necropsy findings. Likewise, no effect of treatment was seen in fetal body weights, fetal sex distribution, or during the fetal external, visceral, or skeletal examinations. The NOEL (noobservable-effect level) for maternal and developmental toxicity was 1000 mg DBPDO/kg/day, the highest dose level administered on gestation days 0 to 19.

Chronic Inhalation Toxicity of Fibrous Glass in Rats and Monkeys

1986 ◽  
Vol 5 (6) ◽  
pp. 545-575 ◽  
Author(s):  
R. I. Mitchell ◽  
D. J. Donofrio ◽  
W. J. Moorma
Keyword(s):  
Clinical Signs ◽  
Inhalation Toxicity ◽  
Potential Health ◽  
Inhalation Study ◽  
Pleural Plaques ◽  
Body Weights ◽  
Table Analysis ◽  
F344 Rats ◽  
Macrophage Aggregates

Numerous reports have shown that fibrous glass has the potential to cause fibrogenic and carcinogenic responses in test animals. The experiments producing significant response have, however, used unrealistic routes of exposure. The increased demand for fibrous glass for insulating purposes where respirable fibers may exist presents considerable concern for potential health problems. Therefore, a long-term inhalation study was conducted with F344 rats and cynomolgus monkeys exposed in treatments characterized by fibers of varying geometry and mass concentrations. A workweek type of exposure (7 hours/day, 5 days/week) was maintained for 18 months with monkeys and 21 months with rats, which were subsequently held to 80% mortality. The evaluation of response included life table analysis, body weights, clinical signs, hematological testing, respiratory function, ophthalmic examinations, clinical biochemical analysis, and gross and microscopic pathological examinations. Both species demonstrated pulmonary macrophage aggregates and granulomas containing fibrous glass. The rats had grossly visible pleural plaques, which were not seen in the monkeys. There was no evidence of pulmonary or mesothelial carcinogenicity or fibrogenicity in either species. There were no other significant responses with the exception of a statistically increased mononuclear cell leukemia in each fiber-exposed rat group.

scholarly journals PENGARUH PEMBERIAN TUAK TERHADAP GAMBARAN HISTOPATOLOGI HATI MENCIT (Mus musculus) ICR JANTAN

2020 ◽  
Vol 11 (2) ◽  
pp. 193
Author(s):  
St Aisyah Sijid ◽  
Cut Muthiadin ◽  
Zulkarnain Zulkarnain ◽  
Ar. Syarif Hidayat
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Liver Damage ◽  
Mus Musculus ◽  
Liver Weight ◽  
Palm Wine ◽  
Icr Mice ◽  
Liver Histopathology ◽  
Mice Liver ◽  
Different Doses

Liver damage or liver disease is caused by many factors, one of which is by consuming drinks that contain alcohol. Tuak is one of the drinks that contain alcohol. This study aims to determine the effect of palm wine administration on the histopathological picture of male ICR mice (Mus musculus) liver. This study used 20 mice consisting of 4 treatments namely P0 = 0 mL / day / head; P1 = 0.1 mL / day / head; P2 = 0.2 mL / day / head and P3 = 0.3 mL / day / head. The parameters observed were body weight of mice, liver weight and liver histopathology of mice. The results showed that administration of palm wine to male ICR mice at different doses gave an influence on the histopathological picture of male ICR mice (Mus musculus).AbstrakKerusakan hati atau penyakit liver disebabkan oleh banyak faktor, salah satunya adalah dengan mengkonsumsi minuman yang mengandung alkohol. Tuak merupakan salah satu minuman yang mengandung alkohol. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian tuak terhadap gambaran histopatologi hati mencit (Mus musculus) ICR jantan. Penelitian ini menggunakan 20 ekor mencit yang terdiri dari 4 perlakuan yaitu P0 = 0 mL/hari/ekor; P1 = 0,1 mL/hari/ekor; P2 = 0,2 mL/hari/ekor dan P3 = 0,3 mL/hari/ekor. Parameter yang diamati adalah berat badan mencit, berat hati dan histopatologi hati mencit. Hasil penelitian menunjukkan bahwa pemberian tuak pada mencit ICR jantan dengan dosis yang berbeda memberikan pengaruh terhadap gambaran histopatologi hati mencit (Mus musculus) ICR jantan.Kata Kunci: Hati, Histopatologi, Mencit, Tuak

scholarly journals Lyophilized B. subtilis ZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study In Wistar Rats

2019 ◽  
Author(s):  
Appala Naidu. B ◽  
Kamala Kannan ◽  
D. P. Santhosh Kumar ◽  
John W.K. Oliver ◽  
Zachary D. Abbott
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Albumin Level ◽  
Repeat Dose ◽  
Oral Gavage ◽  
Toxicological Evaluation ◽  
Body Weights ◽  
Dose Oral

AbstractA 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strain B. subtilis ZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days. B.Subtilis ZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010 and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a non-adverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilized B.Subtilis ZB183 Spores under the test conditions employed.

scholarly journals LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
B. Appala Naidu ◽  
Kamala Kannan ◽  
D. P. Santhosh Kumar ◽  
John W. K. Oliver ◽  
Zachary D. Abbott
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Clinical Signs ◽  
Albumin Level ◽  
Repeat Dose ◽  
Oral Gavage ◽  
Toxicological Evaluation ◽  
Body Weights ◽  
Adverse Effect Level ◽  
Dose Oral

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strainB. subtilisZB183. Lyophilized spores at doses of 109, 1010, and 1011 CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days.B. subtilisZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010and 1011 CFU/kg/day doses without an increase in total protein in males or females and was considered a nonadverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011 CFU/kg body weight/day for lyophilizedB. subtilisZB183 Spores under the test conditions employed.

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