State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences , Guangzhou 510640, P R China.
National Water Quality Laboratory, U.S. Geological Survey , Denver, Colorado 80225, United States.
Environ Sci Technol. 2017 Apr 18;51(8):4434-4444. doi: 10.1021/acs.est.7b00604. Epub 2017 Mar 29.
The increasing use of pharmaceuticals has led to their subsequent input into and release from wastewater treatment plants, with corresponding discharge into surface waters that may subsequently exert adverse effects upon aquatic organisms. Although the distribution of pharmaceuticals in surface water has been extensively studied, the details of uptake, internal distribution, and kinetic processing of pharmaceuticals in exposed fish have received less attention. For this research, we investigated the uptake, disposition, and toxicokinetics of five pharmaceuticals (diclofenac, methocarbamol, rosuvastatin, sulfamethoxazole, and temazepam) in bluegill sunfish (Lepomis macrochirus) exposed to environmentally relevant concentrations (1000-4000 ng L) in a flow-through exposure system. Temazepam and methocarbamol were consistently detected in bluegill biological samples with the highest concentrations in bile of 4, 940, and 180 ng g, respectively, while sulfamethoxazole, diclofenac, and rosuvastatin were only infrequently detected. Over 30-day exposures, the relative magnitude of mean concentrations of temazepam and methocarbamol in biological samples generally followed the order: bile ≫ gut > liver and brain > muscle, plasma, and gill. Ranges of bioconcentration factors (BCFs) in different biological samples were 0.71-3960 and 0.13-48.6 for temazepam and methocarbamol, respectively. Log BCFs were statistically positively correlated to pH adjusted log K (that is, log D), with the strongest relations for liver and brain (r = 0.92 and 0.99, respectively), implying that bioconcentration patterns of ionizable pharmaceuticals depend on molecular status, that is, whether a pharmaceutical is un-ionized or ionized at ambient tissue pH. Methocarbamol and temazepam underwent rapid uptake and elimination in bluegill biological compartments with uptake rate constants (K) and elimination rate constants (K) at 0.0066-0.0330 h and 0.0075-0.0384 h, respectively, and half-lives at 18.1-92.4 h. Exposure to mixtures of diclofenac, methocarbamol, sulfamethoxazole, and temazepam had little or no influence on the uptake and elimination rates, suggesting independent multiple uptake and disposition behaviors of pharmaceuticals by fish would occur when exposed to effluent-influenced surface waters.
随着药品使用量的增加,它们随后被输入和释放到污水处理厂,相应地排放到地表水,可能会对水生生物产生不利影响。尽管已广泛研究了药品在地表水的分布情况,但暴露于鱼类中的药品的摄取、内部分布和动力学处理的细节却受到较少关注。在这项研究中,我们在流动暴露系统中研究了在环境相关浓度(1000-4000ng/L)下五种药品(双氯芬酸、美索巴莫、罗苏伐他汀、磺胺甲恶唑和替马唑仑)在蓝鳃太阳鱼(Lepomis macrochirus)中的摄取、处置和毒代动力学。替马唑仑和美索巴莫在蓝鳃鱼生物样本中始终被检测到,胆汁中的浓度最高,分别为 4940 和 180ng/g,而磺胺甲恶唑、双氯芬酸和罗苏伐他汀则很少被检测到。在 30 天的暴露中,生物样本中替马唑仑和美索巴莫的平均浓度的相对大小通常遵循以下顺序:胆汁>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>,
#include <stdio.h>
int main() {
printf("Enter a number: ");
int n;
scanf("%d", &n);
printf("%d\n", n % 2);
return 0;
}