Carcinogen adducts: use in diagnosis and risk assessment

1994 ◽  
Vol 40 (7) ◽  
pp. 1438-1443 ◽  
Author(s):  
P B Farmer
Keyword(s):  
Mass Spectrometry ◽  
Risk Assessment ◽  
Animal Experiments ◽  
Carcinogenic Risk ◽  
Gas Chromatography Mass Spectrometry ◽  
Low Doses ◽  
Quantitative Measurements ◽  
Fluorescence Measurements ◽  
Genotoxic Carcinogens ◽  
Long Lifetime

Abstract Exposure to genotoxic carcinogens results in the formation of covalently bound adducts of the carcinogens with cellular nucleophilic molecules, including DNA and protein. Quantitative measurements of these adducts may be used to monitor exposure to these carcinogens. The analytical methods required to detect the adducts need to be of exceptional sensitivity and include 32P-postlabeling, immunoassay, and physicochemical techniques (e.g., mass spectrometry or fluorescence measurements). Owing to its accessibility and long lifetime, hemoglobin is also suitable for carcinogen adduct measurement, and techniques based on gas chromatography-mass spectrometry or immunoassay have been developed for this purpose. Although the measurement of adducts is now accepted as a valid means of monitoring exposure to carcinogens, the value of such measurements in indicating carcinogenic risk in humans is less certain. However, adduct concentrations, particularly at low doses of carcinogen, have in several instances been shown to correlate with tumorigenicity in animal experiments.

Identification and measurement of testosterone in plasma and follicular fluid of the mare, using gas chromatography–mass spectrometry associated with isotope dilution

1983 ◽  
Vol 97 (1) ◽  
pp. 51-56 ◽  
Author(s):  
P. Silberzahn ◽  
L. Dehennin ◽  
I. H. Zwaïn ◽  
P. Leymarie
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Follicular Fluid ◽  
Biosynthetic Pathway ◽  
Mammalian Species ◽  
Gas Chromatography Mass Spectrometry ◽  
Plasma Testosterone ◽  
Quantitative Measurements ◽  
Chromatography Mass Spectrometry

Testosterone has been identified by mass spectrometry in blood and follicular fluid aspirated from mature Graafian follicles of mares. Quantitative measurements made by gas chromatography–mass spectrometry have validated the determination of plasma testosterone made by radioimmunoassay. However, because of high levels of epitestosterone (17α-hydroxyandrost-4-en-3-one) in the follicular fluid, radioimmunoassay overestimates the true concentrations of testosterone. The occurrence of testosterone in mare follicular fluid at a concentration which is two orders of magnitude higher than that in peripheral plasma suggests that the follicle may contribute to the production of circulating testosterone. A biosynthetic pathway for oestradiol-17β which involves testosterone is therefore likely to occur in the mare ovary as in many other mammalian species.

scholarly journals Genotoxicity Study on Nicotine and Nicotine-Derived Nitrosamine by Accelerator Mass Spectrometry

Radiocarbon ◽  
1996 ◽  
Vol 38 (2) ◽  
pp. 347-353 ◽  
Author(s):  
X. S. Li ◽  
H. F. Wang ◽  
J. Y. Shi ◽  
X. Y. Wang ◽  
Y. F. Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Dna Adducts ◽  
Accelerator Mass Spectrometry ◽  
Chemical Speciation ◽  
Animal Experiments ◽  
Tobacco Consumption ◽  
Carcinogenic Risk ◽  
Dna Adduction ◽  
Carcinogenic Risk Assessment ◽  
Potential Carcinogen

We have studied DNA adduction with 14C-labeled nicotine and nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by accelerator mass spectrometry (AMS) in mouse liver at doses equivalent to low-level exposure of humans. The dose ranges of nicotine and NNK administered were from 0.4 μg to 4.0×102 μg kg b.w.-1, and from 0.1 μg to 2.0×104 μg kg b.w.-1, respectively. In the exposure of mice to either nicotine or NNK, the number of DNA adducts increased linearly with increasing dose. The detection limit of DNA adducts was 1 adduct per 1011 nucleotide molecules. This limit is 1–4 orders of magnitude lower than that of other techniques used for quantification of DNA adducts. The results of our animal experiments enabled us to speculate that nicotine is a potential carcinogen. According to the procedure for 14C-labeled-NNK synthesis, we discuss the ultimate chemical speciation of NNK bound to DNA. From the animal tests we derived a directly perceivable relation between tobacco consumption and DNA adduction as the carcinogenic risk assessment.

scholarly journals Risk assessment. Principles and consequences

2000 ◽  
Vol 72 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
I. F. H. Purchase
Keyword(s):  
Risk Assessment ◽  
Safety Factor ◽  
Animal Experiments ◽  
Cumulative Risk ◽  
Exposure Data ◽  
Adverse Effect Level ◽  
Genotoxic Carcinogens ◽  
Effect Level ◽  
Unbiased Estimates ◽  
Risk Of Exposure

Risk assessment is an important tool in deciding how to allocate resources to controlling risks. In most cases it is based on hazard data derived from animal experiments and on exposure data from an assessment of the likely or actual exposure of the population of interest. Recent advances have improved the understanding of the use of the no adverse effect level (NOAEL) and safety factor for risk assessment by providing a scientific justification of the 100-fold safety factor. Concern about the risks of exposure by various routes simultaneously (aggregate exposure) and the risks of exposure to mixtures (cumulative risk assessment) have lead to new approaches to these issues. For many years, risk assessment of genotoxic carcinogens has relied on low-dose extrapolation using mathematical models. Recently, these methods are being reconsidered and, in some cases, replaced with the NOAEL/safety factor approach combined with all information on the mechanism of action and the magnitude of the response. It is vitally important to ensure that risk assessment provides accurate and unbiased estimates of risk of exposure so that appropriate measures can be taken to control the risks.

scholarly journals Pesticide residues in bee pollen - validation of the gas chromatography-mass spectrometry multiresidual method and a survey of bee pollens from Slovenia

2021 ◽  
Vol 117 (2) ◽  
pp. 1
Author(s):  
Helena BAŠA ČESNIK
Keyword(s):  
Mass Spectrometry ◽  
Risk Assessment ◽  
Gas Chromatography ◽  
Pesticide Residues ◽  
Solid Phase ◽  
Lower Number ◽  
Gas Chromatography Mass Spectrometry ◽  
Phase Extraction ◽  
Bee Pollen ◽  
Active Substances

A new analytical method for determining environmental pesticide residues in pollen was introduced and validated. The extraction was conducted using acetonitrile, the clean-up using Supelclean Ultra 2400 solid phase extraction cartridges, which contain Grapsphere, anion exchanger, C18 and zirconia-based sorbent, and the determination was conducted using gas chromatography coupled with mass spectrometry. The method was applied in practice. A total of 49 active substances (pesticides) were sought in 30 bee pollen samples gathered from Slovenian beekeepers from all 12 statistical regions of Slovenia. The fungicide azoxystrobin was the only active substance found and was found only in one sample with a concentration of < 0.05 mg kg-1. The active substances sought were not detected in 96.7 % of the samples analysed. The risk assessment revealed that the analysed pollen samples do not represent an unacceptable risk for consumers. The results were compared with those from the literature and the outcome was that bee pollen from Slovenia contained a lower number of active substances at mainly lower contents as compared pollen from some other European countries.

scholarly journals Threshold for Genotoxic Carcinogens: The Central Concern in Carcinogenic Risk Assessment

2012 ◽  
Vol 34 (4) ◽  
pp. 153-156 ◽  
Author(s):  
Shoji Fukushima ◽  
Min Wei ◽  
Anna Kakehashi ◽  
Hideki Wanibuchi
Keyword(s):  
Risk Assessment ◽  
Carcinogenic Risk ◽  
Central Concern ◽  
Genotoxic Carcinogens ◽  
Carcinogenic Risk Assessment

scholarly journals Analysis of Phthalates and Alternative Plasticizers in Gloves by Gas Chromatography–Mass Spectrometry and Liquid Chromatography–UV Detection: A Comparative Study

Toxics ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 200
Author(s):  
Kelly Poitou ◽  
Tiphaine Rogez-Florent ◽  
Marie Lecoeur ◽  
Cécile Danel ◽  
Romain Regnault ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Risk Assessment ◽  
Gas Chromatography ◽  
Essential Feature ◽  
Toxic Substance ◽  
Ease Of Use ◽  
Gas Chromatography Mass Spectrometry ◽  
Laboratory Practice ◽  
Good Laboratory ◽  
Orthogonal Methods

 Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, including phthalates. The purpose of the present study was to develop two orthogonal methods, GC–MS and HPLC–DAD, for the screening of plasticizers in gloves. Performances of these two methods were compared in terms of ease of use, number of analyzed plasticizers, and sample preparation. The two methods were validated and applied for the identification and quantification of plasticizers in ten gloves made with different materials (vinyl, nitrile, latex, and neoprene). Results revealed the presence of three main ones: DEHP, DEHT, and DINP. Additionally, the contents of plasticizers were extremely variable, depending on the glove material. As expected, the results point out a predominant use of plasticizers in vinyl gloves with an amount that should be of concern. While DEHP is classified as a toxic substance for reproduction 1B, it was, however, quantified in the ten different glove samples studied. This study provides new data regarding the plasticizers’ content in protective gloves, which could be useful for risk assessment. 

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