Reproductive Toxicity

ReProTect is a project within the 6th European Framework Program which has developed alternative methods aimed to reduce or replace animal experimentation in the field of reproductive toxicology. In its final year, a ring trial, named the “Feasibility Study”, was conducted, in which 10 blinded chemicals with toxicologically well-documented profiles were analyzed by employing a test battery of 14 in vitro assays. EC50 (half maximal effective concentration) or equivalent endpoints were determined and the test compounds were ranked relative to chemicals previously assayed in the tests of the battery. This comparative analysis together with a weight of evidence approach allowed a robust prediction of adverse effects on fertility and embryonic development of the 10 test chemicals in vivo. In summary, the vast majority of the predictions made based on the in vitro results turned out to be correct when compared to the whole animal data. The procedure used here, a nearest neighbor analysis coupled with a weight of evidence approach, may guide future activities in the field of alternative toxicity testing.

The Sperm Chromatin Structure Assay (SCSA) serves as a tool for measuring clinically important properties of sperm nuclear chromatin integrity. The assay utilizes the metachromatic features of Acridine Orange (AO), a DNA probe, and the principles of flow cytometry (FCM). SCSA data are not well correlated with classical sperm quality parameters and have been solidly shown to predict sub/infertility. This assay is ideally suited to human and animal fertility clinics to assess male sperm DNA integrity as related to fertility potential and embryo development as well as effects of reproductive toxicants. A detailed description of the SCSA follows.

Caffeine and theobromine are purine alkaloids widely consumed as stimulants and snacks in coffee and cocoa based foods and most often as part of ingredients in drugs. Man has enjoyed a long history of consumption of caffeine and theobromine. Recent interest in these two alkaloids, however, is centered on their potential reproductive toxicities. Caffeine and theobromine are now known to cross the placental and blood brain barrier thus potentially inducing fetal malformation by affecting the expression of genes vital in development. The developing fetus may not have developed enzymes for detoxification of these methylxanthine alkaloids via demethylation. There is a need, therefore, to protect the conceptus against 'insults' from teratogens of this nature. Apart from its reproductive toxicity, the presence of caffeine and theobromine in cocoa could limit its potentials as a nourishing food. This is an issue that needs to be addressed by nutritionists and the food industry at la...

Caffeine and theobromine are purine alkaloids widely consumed as stimulants and snacks in coffee and cocoa based foods and most often as part of ingredients in drugs. Man has enjoyed a long history of consumption of caffeine and theobromine. Recent interest in these two alkaloids, however, is centered on their potential reproductive toxicities. Caffeine and theobromine are now known to cross the placental and blood brain barrier thus potentially inducing fetal malformation by affecting the expression of genes vital in development. The developing fetus may not have developed enzymes for detoxification of these methylxanthine alkaloids via demethylation. There is a need, therefore, to protect the conceptus against 'insults' from teratogens of this nature. Apart from its reproductive toxicity, the presence of caffeine and theobromine in cocoa could limit its potentials as a nourishing food. This is an issue that needs to be addressed by nutritionists and the food industry at la...

Many women of childbearing age are exposed to reproductive toxicants in the workplace. This article highlights the need for an evaluation of current occupational exposure guidelines for pregnant women working with hazardous agents that have the potential of being reproductive toxins. Limited information regarding reproductive risks associated with many chemicals in the workplace presents challenges in the establishment of standards that are 'safe' for vulnerable populations, such as the fetus. The management of these risks must take into consideration the limitations of available knowledge as well as individual risk factors that may amplify the likelihood of adverse outcomes. In 1981, Quebec adopted a policy that provides "precautionary leave" or reassignment of pregnant workers to other jobs if they are exposed to a factor suspected to compromise their health or that of their fetus during pregnancy. The advantages and disadvantages of this approach to managing rep...

The link between dietary fats and cardiovascular diseases has necessitateda growing research interest in palm oil, the second largest consumedvegetable oil in the world. Palm oil, obtained from a tropical plant, Elaeis guineensis contains 50% saturated fatty acids, yet it does notpromote atherosclerosis and arterial thrombosis. The saturated fatty acidto unsaturated fatty acid ratio of palm oil is close to unity and it containsa high amount of the antioxidants, β-carotene, and vitamin E. Although palm oil-based diets induce a higher blood cholesterol level thando corn, soybean, safflower seed, and sunflower oils, the consumption ofpalm oil causes the endogenous cholesterol level to drop. Thisphenomenon seems to arise from the presence of the tocotrienols and thepeculiar isomeric position of its fatty acids.The benefits of palm oil to health include reduction in risk of arterialthrombosis and atherosclerosis, inhibition of endogenous cholesterolbiosynthesis, platelet aggregation, and reduction in blood pressure. Palm oilhas been used in the fresh state and/or at various levels of oxidation.Oxidation is a result of processing the oil for various culinary purposes.However, a considerable amount of the commonly used palm oil is in theoxidized state, which poses potential dangers to the biochemical andphysiological functions of the body. Unlike fresh palm oil, oxidized palm oilinduces an adverse lipid profile, reproductive toxicity and toxicity of thekidney, lung, liver, and heart. This may be as a result of the generation oftoxicants brought on by oxidation. In contrast to oxidized palm oil, red orrefined palm oil at moderate levels in the diet of experimental animalspromotes efficient utilization of nutrients, favorable body weight gains,induction of hepatic drug metabolizing enzymes, adequatehemoglobinization of red cells and improvement of immune function. However, high palm oil levels in the diet induce toxicity to the liver asshown by loss of cellular radial architecture and cell size reductions whichare corroborated by alanine transaminase to aspartate transaminase ratioswhich are higher than unity.The consumption of moderate amounts of palm oil and reduction in thelevel of oxidation may reduce the health risk believed to be associated withthe consumption of palm oil. Red palm oil, by virtue of itsβ-carotene content, may protect against vitamin A deficiency andcertain forms of cancer.

Phthalate esters are ubiquitous environmental contaminants that in general display low-toxicity. Overall, the reproductive effects of these compounds are well characterized in adult's animals, with gonadal injury observed after high dose exposure. However, results of recent transgeneration studies indicate that the reproductive system of developing animals is particularly vulnerable to certain phthalates. The phenotypic alterations observed in male offspring rats exposed during the perinatal period have remarkable similarities with common human reproductive disorders, including cryptorchidism, hypospadias and low-sperm counts. Recent results also indicate that high phthalate doses can adversely affect adult and developing female rats. However, the main question involving phthalates is whether the current level of human exposure is sufficient to adversely affect male and/or female reproductive health. Here, we review the reproductive toxicity data of phthalates in adult and developing animals as well as possible modes of action. In addition, we briefly discuss the relevance of animal studies to humans in light of recent epidemiological data and experimental research with low (human relevant) doses. Finally, we point out some critical issues that should be addressed in order to clarify the implications of phthalates for human reproduction.

This article describes a standardized test method for determining the effect of chemical substances on the reproduction of the earthworm Eisenia fetida andrei. It is based on the existing guidelines for acute toxicity testing with earthworms, and for reasons of standardization the same artificial soil substrate and earthworm species were chosen as prescribed by these guidelines. After being preconditioned for