Oral (gavage), in utero and post-natal exposure of Sprague–Dawley rats to low doses of tributyltin chloride

2004 ◽  
Vol 42 (2) ◽  
pp. 221-235 ◽  
Author(s):  
H Tryphonas ◽  
G Cooke ◽  
D Caldwell ◽  
G Bondy ◽  
M Parenteau ◽  
...  
Author(s):  
Shu-Chieh Hu ◽  
Matthew S Bryant ◽  
Estatira Sepehr ◽  
Hyun-Ki Kang ◽  
Raul Trbojevich ◽  
...  

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.


2004 ◽  
Vol 32 (4) ◽  
pp. 371-374 ◽  
Author(s):  
Woo-Chan Son ◽  
Chirukandath Gopinath

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague—Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50—80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50—80 weeks and at 2 years was pituitary adenoma.


Toxicology ◽  
2002 ◽  
Vol 179 (3) ◽  
pp. 183-196 ◽  
Author(s):  
Steve Teo ◽  
David Stirling ◽  
Steve Thomas ◽  
Alan Hoberman ◽  
Anthony Kiorpes ◽  
...  

2011 ◽  
Vol 39 (4) ◽  
pp. 614-622 ◽  
Author(s):  
Pramod S. Terse ◽  
Jerry D. Johnson ◽  
Michael A. Hawk ◽  
Glenn D. Ritchie ◽  
Michael J. Ryan ◽  
...  

1988 ◽  
Vol 7 (5) ◽  
pp. 603-615 ◽  
Author(s):  
G.T. Gallagher ◽  
E.A. Maull ◽  
K. Kovacs ◽  
S. Szabo

Male Sprague-Dawley rats ingested 0, 20 ppm, or 500 ppm of acrylonitrile in drinking water for 2 years. Rats receiving 500 ppm of acrylonitrile exhibited early mortality and retarded weight gain. Tumors of Zymbal's gland were associated in dose-response fashion with acrylonitrile exposure. Age-associated incidence of pituitary adenomas containing immunoreactive prolactin was decreased in acrylonitrile-treated rats. A decrease in pituitary tumor incidence also was observed in rats treated with low doses of acrylonitrile, suggesting that reduction in this tumor frequency was not because of early death. No increases were found in tumors of other organ systems, but a trend toward development of forestomach papillomas was noted in rats receiving the highest concentration of acrylonitrile.


Sign in / Sign up

Export Citation Format

Share Document