scholarly journals Proposed Key Characteristics of Male Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Evidence in Human Health Hazard Assessments

2019 ◽  
Vol 127 (6) ◽  
pp. 065001 ◽  
Author(s):  
Xabier Arzuaga ◽  
Martyn T. Smith ◽  
Catherine F. Gibbons ◽  
Niels E. Skakkebæk ◽  
Erin E. Yost ◽  
...  
Keyword(s):  
Human Health ◽  
Health Hazard ◽  
Key Characteristics ◽  
Hazard Assessments ◽  
Reproductive Toxicants ◽  
Human Health Hazard

Mouse-specific carcinogens: an assessment of hazard and significance for validation of short-term carcinogenicity bioassays in transgenic mice

1998 ◽  
Vol 17 (4) ◽  
pp. 193-205 ◽  
Author(s):  
Jon M Battershill ◽  
R J Fielder
Keyword(s):  
Transgenic Mice ◽  
Human Health ◽  
Health Hazard ◽  
Mouse Bioassay ◽  
Pharmacokinetic Data ◽  
Potential Hazard ◽  
Short Term ◽  
Genotoxic Carcinogens ◽  
Hazard Assessments ◽  
Human Health Hazard

1 The International Conference on the Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for human use (ICH) has agreed that bioassay data from only one species, the rat, supported by appropriate mutagenicity and pharmacokinetic data and also information from new (unvalidated) short term in vivo screening tests for potential carcinogenicity, could be used for the licensing of human medicines. This proposal has been supported by reviews of the utility of testing pharmaceuticals in the mouse which have concluded that the mouse bioassay contributes little to regulatory decisions. The current review was undertaken to identify `genuine' mouse-specific carcinogens using the Gold Carcinogenicity Potency Database (CPD) for the initial identification of potential mouse-specific carcinogens from published literature. Hazard assessments were completed for these chemicals with particular attention focused on the `genuine' mouse-specific carcinogens. The significance of such chemicals has been discussed together with consideration of on-going work on the validation of short-term carcinogenicity bioas-says using transgenic mice. 2 Seventy-six potential mouse specific carcinogens were identified through the Gold Carcinogenicity Potency Database. Following more detailed consideration a total of ten chemicals were excluded from further consideration (three were multispecies carcinogens, five were considered to be non-carcinogenic in the mouse, and the data for two were uninterpretable). The review focused on the remaining 66 chemicals. There was equivocal evidence of carcinogenicity to the rat for 28 chemicals and inadequate data for a further 23 chemicals. Fifteen `genuine' mouse-specific carcinogens were identified. These 15 chemicals comprise two genotoxic mouse-specific carcinogens (N-methylolacrylamide (924-42-5), 2,6-Dichloro-p-phenylenedia-mine (609-20-1); five non-genotoxic mouse-specific carcinogens 2-Aminobiphenyl.HCl (2185-92-4), Captan (133-06-2), Dieldrin (60-57-7), Diethylhexyladipate (103-23-1), and Probenicid (57-66-9); five mouse-specific carcinogens with equivocal evidence of mutagenicity were identified; (2,4-diaminophenol.2HCl (137-09-7), Dipyrone (68-89-3), Ozone (10028-15-6), Vinylidene chloride (75-35-4), and Zearalenone (17924-92-4)), and three mouse-specific carcinogens with inadequate mutagenicity data (Benzaldehyde (100-52-7), Piperonyl sulphoxide (120-62-7), Ripazepam (26308-28-1)). 3 It is suggested that the two genotoxic mouse carcinogens would have been considered as potential carcinogens in the absence of a mouse bioassay. Of the five non-genotoxic mouse-specific carcinogens; three induced tumours in mouse liver only and are considered as being of low potential hazard to human health. The remaining two chemicals would have been missed in the absence of a mouse bioassay (2-aminobiphenyl (2185-92-4) and captan (133-06-2)) and thus are good candidates for evaluation in the short term bioassays in transgenic mice currently being validated. 4 The hardest group of mouse-specific carcinogens to evaluate are those for which there is equivocal or inadequate mutagenicity data. The difficulty in evaluating these particular chemicals emphasises the need for adequate mutagenicity data in addition to adequate carcinogenicity data in order to assess potential hazards to human health. Hazard assessments and a consideration of the potential role for short-term bioassays in transgenic mice for the eight chemicals in this subgroup are presented. 5 A number of general conclusions have been derived from this review. Firstly, there are insufficient published genotoxicity data to allow a full assessment of mutagenic potential for 57/76 of the potential mouse-specific carcinogens identified from the CPD. This is surprising given the clear value of such data in interpreting bioassay results and the much greater resources required for carcinogenicity bioassays. Second, the newly proposed short-term tests in transgenic mice must be able to identify genotoxic carcinogens and this must include the very few mouse-specific genotoxic carcinogens. Third, there are relatively few non-genotoxic `genuine' mouse-specific carcinogens identifiable from the CPD, which may pose a significant human health hazard. 6 It is suggested that regulatory and industry data files for chemicals other than pharmaceuticals could be reviewed in order to ascertain the full significance of mouse only carcinogens.

scholarly journals Nanoparticles, human health hazard and regulation

2009 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Anthony Seaton ◽  
Lang Tran ◽  
Robert Aitken ◽  
Kenneth Donaldson
Keyword(s):  
Human Health ◽  
Human Exposure ◽  
Scientific Evidence ◽  
Health Hazard ◽  
New Developments ◽  
New Science ◽  
Combustion Particles ◽  
Human Health Hazard ◽  
Physical Principles

New developments in technology usually entail some hazard as well as advantage to a society. Hazard of a material translates into risk by exposure of humans and/or their environment to the agent in question, and risk is reduced by control of exposure, usually guided by regulation based on understanding of the mechanisms of harm. We illustrate risks relating to the causation of diseases associated with exposure to aerosols of combustion particles and asbestos, leading to paradigms of particle toxicity, and discuss analogies with potential exposure to manufactured nanoparticles (NPs). We review the current understanding of the hazard of NPs derived from the new science of nanotoxicology and the limited research to date into human exposure to these particles. We identify gaps in knowledge relating to the properties of NPs that might determine toxicity and in understanding the most appropriate ways both to measure this in the laboratory and to assess it in the workplace. Nevertheless, we point out that physical principles governing the behaviour of such particles allow determination of practical methods of protecting those potentially exposed. Finally, we discuss the early steps towards regulation and the difficulties facing regulators in controlling potentially harmful exposures in the absence of sufficient scientific evidence.

Suburban air quality: Human health hazard assessment of potentially toxic elements in PM10

Chemosphere ◽  
2017 ◽  
Vol 177 ◽  
pp. 284-291 ◽  
Author(s):  
Laura Megido ◽  
Beatriz Suárez-Peña ◽  
Luis Negral ◽  
Leonor Castrillón ◽  
Yolanda Fernández-Nava
Keyword(s):  
Air Quality ◽  
Human Health ◽  
Hazard Assessment ◽  
Toxic Elements ◽  
Health Hazard ◽  
Potentially Toxic Elements ◽  
Human Health Hazard

BRUCELLOSIS AS A HUMAN HEALTH HAZARD IN AUSTRALIA

1974 ◽  
Vol 50 (5) ◽  
pp. 209-215 ◽  
Author(s):  
G. G. Alton ◽  
J. Gulasekharam
Keyword(s):  
Human Health ◽  
Health Hazard ◽  
Human Health Hazard

scholarly journals Studies on well water and possible health risks in Katsina, Nigeria

1983 ◽  
Vol 90 (2) ◽  
pp. 199-205 ◽  
Author(s):  
A. A. Adesiyun ◽  
J. O. Adekeye ◽  
J. U. Umoh ◽  
M. Nadarajah
Keyword(s):  
Human Health ◽  
Water Table ◽  
Health Risks ◽  
Significant Relationship ◽  
Health Hazard ◽  
Ground Level ◽  
Well Water ◽  
Faecal Coliforms ◽  
Gram Negative ◽  
Human Health Hazard

SUMMARYWell water was sampled from all four major wards in Katsina town. All 20 samples taken showed high coliform counts. Sixty-five per cent contained ≥ 2400 coliforms per 100 ml while the remainder had counts ranging from 79 to 920. Faecal coliforms and non-cholera vibrios were detected in all samples. There was no significant relationship between the coliform counts and the distances of latrines to wells, water table to ground level, slope relationship between wells and latrines, the pH of water and whether the wells were left permanently open or not.Salmonellasp.,Enterobactersp. andPseudomonassp. were each isolated from about 10% of the samples, whileProteussp. was isolated from 40%,Citrobactersp. 15%,Alcaligenessp. 5% and an unidentified Gram-negative rod from 5%.Only 2 (10%) of the sampled households, representing 23 (9·6%) of the 239 people exposed to well-water had pipeborne water in addition. It was concluded that well water in Katsina town could be a human health hazard.

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