Some aspects relating to the evaluation of the effects of chemicals on male fertility.
01 Jun 2003-Regulatory Toxicology and Pharmacology (Regul Toxicol Pharmacol)-Vol. 37, Iss: 3, pp 356-369
TL;DR: Of the endpoints investigated, the most sensitive proved to be histopathology of the testes, which showed a higher sensitivity than fertility parameters, and in most cases, not only one but several endpoints were affected.
About: This article is published in Regulatory Toxicology and Pharmacology.The article was published on 2003-06-01. It has received 99 citations till now. The article focuses on the topics: Sperm motility & Reproductive toxicity.
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TL;DR: Under safety aspects, it appears wise to consider established in vivo tests to be indispensable as basic tools for hazard and risk assessment with respect to systemic single and repeated dose toxicity, sensitisation, carcinogenicity and reproductive toxicity, especially regarding quantitative aspects of risk assessment.
Abstract: During the last two decades, substantial efforts have been made towards the development and international acceptance of alternative methods to safety studies using laboratory animals. In the EU, challenging timelines for phasing out of many standard tests using laboratory animals were established in the seventh Amending Directive 2003/15/EC to Cosmetics Directive 76/768/EEC. In continuation of this policy, the new European Chemicals Legislation (REACH) favours alternative methods to conventional in vivo testing, if validated and appropriate. Even alternative methods in the status of prevalidation or validation, but without scientific or regulatory acceptance may be used under certain conditions. Considerable progress in the establishment of alternative methods has been made in some fields, in particular with respect to methods predicting local toxic effects and genotoxicity. In more complex important fields of safety and risk assessment such as systemic single and repeated dose toxicity, toxicokinetics, sensitisation, reproductive toxicity and carcinogenicity, it is expected that the development and validation of in silico methods, testing batteries (in vitro and in silico) and tiered testing systems will have to overcome many scientific and regulatory obstacles which makes it extremely difficult to predict the outcome and the time needed. The main reasons are the complexity and limited knowledge of the biological processes involved on one hand and the long time frame until validation and regulatory acceptance of an alternative method on the other. New approaches in safety testing and evaluation using “Integrated Testing Strategies” (ITS) (including combinations of existing data, the use of chemical categories/grouping, in vitro tests and QSAR) that have not been validated or not gained wide acceptance in the scientific community and by regulatory authorities will need a thorough justification of their appropriateness for a given purpose. This requires the availability of knowledge and experience of experts in toxicology. The challenging deadlines for phasing out of in vivo tests in the Cosmetics Amending Directive 2003/15/EC appear unrealistic. Likewise, we expect that the application of validated alternative methods will only have a small or moderate impact on the reduction of in vivo tests under the regimen of REACH, provided that at least the same level of protection of human health as in the past is envisaged. As a consequence, under safety aspects, it appears wise to consider established in vivo tests to be indispensable as basic tools for hazard and risk assessment with respect to systemic single and repeated dose toxicity, sensitisation, carcinogenicity and reproductive toxicity, especially regarding quantitative aspects of risk assessment such as NOAELs, LOAELs and health-related limit values derived from them. Based on the overall evaluation in this review, the authors are of the opinion that in the short- and mid-term, the strategy of the development of alternative methods should be more directed towards the refinement or reduction of in vivo tests. The lessons learnt during these efforts will provide a substantial contribution towards the replacement initiatives in the long-term.
275 citations
Additional excerpts
...…et al. 2007), peroxisome proliferators (Tamura et al. 2006), 2-acetylaminoXuorene, 2-nitropropane, 2-nitrop-phenylenediamine, 2,4-diaminotoluene (Nakayama et al. 2006), N-ethyl-N-nitrosourea (Okamura et al. 2004), ochra- toxin A (Arbillaga et al. 2007), aristolochic acid (Stemmer et al. 2006),…...
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TL;DR: The evidence for an adverse effect on male reproduction of several occupational and environmental exposures and toxicants, such as heat, ionizing radiation, inorganic lead, dibromochloropropane, ethyleneDibromide, some ethylene glycol ethers, carbon disulfide and welding operations, is strongly supported in well-designed epidemiological studies.
Abstract: Recently, many studies have found a decrease in semen quality which has increased the focus on male reproductive health. Occupational hazards are by far the best documented in reproductive epidemiological research. Generally, occupational exposures have been divided into physical exposures (heat and radiation), chemical exposures (solvents and pesticides), psychological exposures (distress), exposure to metals and welding. The recent and/or most important epidemiological studies exploring the effect of occupational exposures on semen quality and fecundity, the ability to conceive, are reviewed. The evidence for an adverse effect on male reproduction of several occupational and environmental exposures and toxicants, such as heat, ionizing radiation, inorganic lead, dibromochloropropane, ethylene dibromide, some ethylene glycol ethers, carbon disulfide and welding operations, is strongly supported in well-designed epidemiological studies. For other agents, the association is only suspected or suggested and needs further evaluation before conclusions can be drawn. It is also important to bear in mind that many workers in the non-Western world still are exposed to substances that are banned in the Western world, sometimes in high concentrations.
164 citations
TL;DR: This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men and investigates the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.
Abstract: A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identified and discussed. A particular attention is given to the studies considering influence of concomitant exposure to various metals. These studies have generally confirmed that even moderate- to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.
127 citations
Cites background from "Some aspects relating to the evalua..."
...Damage to the sperm membrane reduces sperm's motility and ability to fuse with the oocyte, whereas damage to sperm DNA compromises paternal genomic contribution to the embryo (49) and increases the risk of infertility, miscarriage, or serious disease in the offspring (56)....
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...As for boron, there is no clear evidence that occupational exposure impairs sperm concentration, motility, morphology, or DNA integrity (95-97)....
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...The disruption of spermatogenesis in men (Table 1) at any stage of cell differentiation can decrease the total sperm count, increase the abnormal sperm count, impair the stability of sperm chromatin or damage sperm DNA (43)....
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...Several metals, including iron, copper, nickel, lead, and cadmium, may increase ROS production, decrease glutathione and other antioxidant levels, enhance the lipid peroxidation of the cell membrane, cause apoptosis, and contribute to the oxidative damage of DNA (52-55)....
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TL;DR: It is indicated that in rats short‐term exposure to 3‐MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity, and the established TDI of 2 μg/kg bw per day is not exceeded in the adult population.
Abstract: The Panel wishes to thank the following for the support provided to this scientific output: the experts of the EFSA Standing Working Group on Benchmark Dose: Marc Aerts, Diane Benford, Lutz Edler, Wim Mennes, Josef Rudolf Schlatter and Wout Slob. Adopted: 21 November 2017 This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2016.4426/full
100 citations
Cites background from "Some aspects relating to the evalua..."
...Furthermore, it is known that male rat fertility is not affected by small changes in sperm count and successful fertilisation occurs even in the presence of 90% depletion of sperm reserves (see e.g. Mangelsdorf et al., 2003; Perobelli et al., 2012)....
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TL;DR: DIBP is supported as a children's health concern and indicate that male reproductive and developmental toxicities are hazards of DIBP exposure, with some evidence for female reproductive and liver toxicity.
93 citations
References
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Book•
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TL;DR: All with an interest in tumours will find something to stimulate them in this book but even these items are to some extent outweighed by the insight given into the thoughts and policies of this fascinating country.
Abstract: It is one of the anomalies of political history that the international medical world has, until recently, been better informed about cancer patterns and cancer research in tropical Africa than in China. Following the overthrow of the 'Gang of Four' a team of US oncologists travelled widely through that vast country, and this book is a record of what they saw. It gives a detailed account of cancer epidemiology, research, diagnosis, and treatment, and of the medico-political background. Most people are familiar with what seems to western eyes to be a curious combination of traditional medicine (acupuncture and herbal therapy) and of high technology, particularly in the field of surgery. Fewer may be aware of the interesting epidemiological studies which have shown high incidence areas of oesophageal, nasopharyngeal, and hepatic carcinoma; of the geographical association of some of these tumours with a high incidence in domestic animals; or of the diagnosis of precancerous oesophageal lesions by cytology obtained by barefoot doctors. All with an interest in tumours will find something to stimulate them in this book but even these items are to some extent outweighed by the insight given into the thoughts and policies of this fascinating country.
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