动力学衍生最大剂量 (KMD) 表明乙基对人类缺乏致癌性
Lyle D Burgoon1, Christopher J Borgert2, Claudio Fuentes3
1Raptor Pharm & Tox, Ltd, Apex, NC, USA.
Archives of toxicology
|December 7, 2023
概括
乙基二烯 (乙二烯) 是一种基二烯.
科学领域:
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
- 风险评估 风险评估
背景情况:
- 暴露于乙烯的动物中的新形成性病变可能是高剂量效应.
- 消除动力学的和可以导致高剂量的质量不同的毒性.
研究的目的:
- 为了测试乙基诱导的瘤病变是否是高剂量现象,这是由于和排泄动力学.
- 估计老鼠和人类的乙的动力学导出最大剂量 (KMD).
主要方法:
- 贝叶斯模型被用来估计乙基清除动力学的Vmax和Km.
- 迈凯利斯-门方程应用于来自老鼠和人类的动力数据.
- 根据估计的动力参数计算KMD范围.
主要成果:
- 静脉乙基的KMD范围估计在老鼠的8-17毫克/升和人类的10-18毫克/升之间.
- 这些静脉度相当于吸入水平约为200 ppm.
- 已识别的KMD显著高于人类典型暴露水平.
结论:
- 甲诱导的瘤病变在动物中很可能是高剂量的现象,是和排泄的次要原因.
- 在可预见的暴露条件下,乙对人类没有可信的癌症风险.
- 未来的风险评估应考虑KMD,并避免高剂量的动物数据乙.
更多相关视频
12:15Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
8.7K
11:38High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
12.3K
相关概念视频
Mutagenicity and Carcinogenicity
1.3K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.3K
Carboxylic Acids to Methylesters: Alkylation using Diazomethane
2.2K
Carboxylic acids react with diazomethane in an ether solvent via alkylation at the carboxylate oxygen atom to give methyl esters of the corresponding acid with excellent yields.
2.2K
NMR Spectroscopy of Benzene Derivatives
8.3K
Simple unsubstituted benzene has six aromatic protons, all chemically equivalent. Therefore, benzene exhibits only a singlet peak at δ 7.3 ppm in the 1H NMR spectrum. The observed shift is far downfield because the aromatic ring current strongly deshields the protons. Any substitution on the benzene ring makes the aromatic protons nonequivalent, and the protons split each other. The peak is, therefore, no longer a singlet and the splitting pattern and their associated coupling...
8.3K
Mass Spectrometry: Cycloalkane Fragmentation
1.4K
In mass spectrometry, cycloalkanes exhibit distinct fragmentation patterns due to the inherent stability of their molecular ions compared to linear or branched alkanes. The ring structure of cycloalkanes provides additional stability to the molecular ions, often resulting in prominent ion peaks in the mass spectrum.
For example, cyclohexane molecular ions have a mass-to-charge ratio (m/z) of 84, which tends to produce a stronger signal than linear alkanes like hexane. This stability comes from...
For example, cyclohexane molecular ions have a mass-to-charge ratio (m/z) of 84, which tends to produce a stronger signal than linear alkanes like hexane. This stability comes from...
1.4K
Combustion Energy: A Measure of Stability in Alkanes and Cycloalkanes
6.4K
The low reactivity in alkanes can be attributed to the non-polar nature of C–C and C–H σ bonds. Alkanes, therefore, were initially termed as “paraffins,” derived from the Latin words: parum, meaning “too little,” and affinis, meaning “affinity.”
Alkanes undergo combustion in the presence of excess oxygen and high-temperature conditions to give carbon dioxide and water. A combustion reaction is the energy source in natural gas, liquified...
Alkanes undergo combustion in the presence of excess oxygen and high-temperature conditions to give carbon dioxide and water. A combustion reaction is the energy source in natural gas, liquified...
6.4K
Structure of Benzene: Kekulé Model
9.1K
In 1865, August Kekule suggested the structure of benzene according to the structural theory of organic chemistry based on the three assertions—formula of benzene is C6H6, all the hydrogens of benzene are equivalent, and each carbon must have four bonds due to its tetravalency.
He proposed that benzene has a cyclic structure of six carbon atoms attached to one hydrogen atom each, with three alternating pi bonds.
He proposed that benzene has a cyclic structure of six carbon atoms attached to one hydrogen atom each, with three alternating pi bonds.
9.1K
