Environmentally induced oxidative stress in aquatic animals

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

/pdf/edc-2-the-endocrine-society-s-second-scientific-statement-on-4hbb1iz0o3.pdf

EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

Pesticides are one of the major inputs used for increasing agricultural productivity of crops. The pesticide residues, left to variable extent in the food materials after harvesting, are beyond the control of consumer and have deleterious effect on human health. The presence of pesticide residues is a major bottleneck in the international trade of food commodities. The localization of pesticides in foods varies with the nature of pesticide molecule, type and portion of food material and environmental factors. The food crops treated with pesticides invariably contain unpredictable amount of these chemicals, therefore, it becomes imperative to find out some alternatives for decontamination of foods. The washing with water or soaking in solutions of salt and some chemicals e.g. chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid, hydroxy peracetic acid, iprodione and detergents are reported to be highly effective in reducing the level of pesticides. Preparatory steps like peeling, trimming etc. remove the residues from outer portions. Various thermal processing treatments like pasteurization, blanching, boiling, cooking, steaming, canning, scrambling etc. have been found valuable in degradation of various pesticides depending upon the type of pesticide and length of treatment. Preservation techniques like drying or dehydration and concentration increase the pesticide content many folds due to concentration effect. Many other techniques like refining, fermentation and curing have been reported to affect the pesticide level in foods to varied extent. Milling, baking, wine making, malting and brewing resulted in lowering of pesticide residue level in the end products. Post harvest treatments and cold storage have also been found effective. Many of the decontamination techniques bring down the concentration of pesticides below MRL. However, the diminution effect depends upon the initial concentration at the time of harvest, substrate/food and type of pesticide. There is diversified information available in literature on the effect of preparation, processing and subsequent handling and storage of foods on pesticide residues which has been compiled in this article.

/pdf/effect-of-handling-and-processing-on-pesticide-residues-in-ussfn9ndlw.pdf

Effect of handling and processing on pesticide residues in food- a review

Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions.

OECD Guidelines for Testing of Chemicals

Time-related changes in potential factors involved in hepatocarcinogenesis by DDT were investigated in a 4-week and a 2-year feeding studies of p,p'-DDT with F344 rats. In the 4-week study with males at doses of 50, 160, and 500 ppm, cell proliferation and gap junctional intercellular communication (GJIC) were examined after 1, 2, 3, 7, 14, and 28 days. Cell proliferation was enhanced within 3 days at any dose level, but returned to normal after 7 days, whereas GJIC was inhibited throughout the study. In the 2-year study with both sexes at doses of 5, 50, and 500 ppm, cell proliferation, GJIC, enzyme induction, and oxidative stress were investigated after 26, 52, 78, and 104 weeks. Males and females showed an inhibition of GJIC and increases in P450 isozymes (CYP2B1 and CYP3A2) in a dose-dependent manner at all time points, but no significant change in cell proliferation. Lipid peroxide for males at 50 and 500 ppm and 8-hydroxydeoxyguanosine for both sexes at 500 ppm were elevated throughout the study. Hi...

Mechanisms of promotion and progression of preneoplastic lesions in hepatocarcinogenesis by DDT in F344 rats.

A two-generation reproductive toxicity study was conducted with 2,4-dichlorophenol (2,4-DCP), an agent suspected of exerting endocrine disrupting effects. Wistar-Hannover rats, 24/sex/group, were given diet containing 2,4-DCP at dose levels of 0, 500, 2000 or 8000 ppm to examine the potential effects of the test substance on parental animals and their offspring over 2 successive generations. Neither clear systemic nor reproductive toxicity of 2,4-DCP was apparent in the 500 ppm group. In the 2000 ppm group, mean body weight gain and food consumption of females were lowered significantly during the treatment period. Effects on body weights and food consumption were more serious in the 8000 ppm group, both males and females being significantly affected. Reproductive effects of the test substance were also observed in the 2000 and 8000 ppm groups dose-dependently. Observations included significantly increased uterine weights of F1 and/or F2 female weanlings and reduced numbers of implantation sites and live births of F1 parental females. These results suggest that 2,4-DCP has weak reproductive toxicity, possibly based on endocrine activity. However, the basic mechanisms for apparent estrogenic effects of 2,4-DCP remain to be elucidated.

A two-generation reproductive toxicity study of 2,4-dichlorophenol in rats

The effects of processing and cooking on the levels of pesticide residues in wheat samples were investigated for 13 pesticides in pre-harvest (Pre, 9 pesticides) and post-harvest (Post, 6 pesticides) samples. In the milling process, the transfer ratios (%, total pesticide residue amount in product/that in wheat grain) of wheat bran were greater than 70% and 80% for pre-harvest and post-harvest samples, respectively. The transfer ratios of flour ranged from 1.7% to 23% (Pre) and 4.0% to 11% (Post). There was no significant difference in transfer ratio among the pesticides investigated. The processing factors (Pf, the concentration (mg/kg) of pesticide in product/that in the wheat grain) of flour ranged from 0.030 to 0.40 (Pre) and 0.069 to 0.18 (Post). The values in pre-harvest samples were higher than those in post-harvest samples. Investigation of changes of pesticide residues during processing and/or cooking is useful not only to establish MRLs, but also to recognize actual levels of pesticide residues in food.

Effects of processing and cooking on the levels of pesticide residues in wheat samples

A two-generation reproduction toxicity study was conducted in rats with a reference estrogenic pesticide, methoxychlor, to validate the sensitivity and competency of current guidelines recommended by the United States Environmental Protection Agency; Japanese Ministry of Agriculture, Forestry and Fisheries; and Organisation for Economic Co-operation and Development for predicting reproductive toxicity of the test compound based on estrogenic endocrine disrupting effects. Both sexes of SD rats were exposed to methoxychlor in the diet at concentrations of 0, 10, 500 and 1500 ppm for two successive generations. The present study has successfully detected estrogenic activities and reproductive toxicities of methoxychlor, as well as its systemic toxicity. Body weights, body weight gains and food consumption of both sexes of animals were suppressed significantly in the 500 and 1500 ppm groups. Typical reproductive toxicities observed in females of these groups included, but were not limited to, prolonged estrous cycle, reduced fertility, decreased numbers of implantation sites and newborns, decreased ovary weights and/or increased incidences of cystic ovary. Uterine weights of weanlings increased significantly in these groups, suggesting that the sensitivity of this parameter for predicting estrogenic ability of the test compound is comparable to that of the uterotrophic assay. Reproductive toxicities of methoxychlor seemed less potent in males than in females. Methoxychlor delayed preputial separation and significantly reduced sperm counts and reproductive organ weights of males of the 500 and/or 1500 ppm groups; however, most males that failed to impregnate females in the same group showed normal fertility when they were re-mated with untreated females. Neither systemic nor reproductive toxicities appeared in the 10 ppm group.

Two-generation reproduction toxicity study in rats with methoxychlor

DDT, an organochlorine pesticide, has been cited as a representative chemical suspected of having endocrine disrupting effects. In this study, the potential endocrine disrupting activities of p,p'-DDT, a major component of DDT, were investigated in rats in a 2-generation reproduction toxicity study in accordance with the most current test guidelines of the Ministry of Agriculture, Forestry and Fisheries in Japan, Organization for Economic Cooperation and Development (OECD) and United States Environmental Protection Agency (USEPA) with some modifications and additions. p,p'-DDT was given to parental rats at dietary levels of 0, 5, 50 or 350 ppm. Systemic toxicities in the parental animals consisted of tremors and subsequent deaths (females only) and/or pathological alterations of the liver (both sexes of animals) of the 2 higher dose groups. Reproductive and postnatal developmental toxicities were not evident up to the highest dose level except for the decreased pup viability index on postnatal day 21 in the 350 ppm group. Changes in serum estradiol and progesterone levels and/or a delay in male sexual maturation were noted in the 2 higher dose groups in a dose-dependent fashion, suggesting alterations of endogenous endocrine functions. However, these changes never resulted in substantial reproductive disorders.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1741-4520.2006.00110.x

Machiko Saka

Papers

Mechanisms of promotion and progression of preneoplastic lesions in hepatocarcinogenesis by DDT in F344 rats.

A two-generation reproductive toxicity study of 2,4-dichlorophenol in rats

Effects of processing and cooking on the levels of pesticide residues in wheat samples

Two-generation reproduction toxicity study in rats with methoxychlor

Two‐generation reproduction toxicity study in rats with 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane (p,p′‐DDT)