Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes?

BACKGROUND: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. OBJECTIVES: We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. METHODS: We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. RESULTS: Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. CONCLUSIONS: Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans.

The Pine River statement: human health consequences of DDT use.

OBJECTIVES: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. DATA SOURCES AND EXTRACTION: We conducted a PubMed search in October 2008 and retrieved 494 studies. DATA SYNTHESIS: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. CONCLUSIONS: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.

Chemical exposures in the workplace: effect on breast cancer risk among women.

Occupational health nurses need to be aware of the current science on breast cancer risks in the workplace because they are risk communicators for employees and their families. Occupational health nurses can serve as advocates for necessary research ultimately leading to risk reduction and prevention strategies in the workplace. Current research suggests exposure to organic solvents, metals, acid mists, sterilizing agents (ethylene oxide), some pesticides, light at night (shift work), and tobacco smoke increases breast cancer risk among women in occupational settings. Animal cancer bioassays conducted by the National Toxicology Program indicate more than 40 chemicals can induce mammary tumors, and most of these are still in production. A variety of occupations worldwide, including health care providers and metal, textile, dye, rubber, and plastic manufacturing workers, have been identified as having some evidence of higher breast cancer risk. Although some chemical exposures are suspected to affect breast cancer risk, estimates of or actual exposures to these chemicals in the workplace often have not been determined. Research needed to better identify breast cancer risks in occupational settings includes monitoring breast cancer incidence in occupations with exposures to suspected carcinogens, characterizing chemical exposures by job type and task, determining whether potential gender differences affect chemical exposures, and using molecular approaches to identify gene-environment interactions.

Ochratoxin a: its cancer risk and potential for exposure.

Ochratoxin A (OA) is a naturally occurring mycotoxin known to contaminate a variety of foods and beverages. The cancer risk posed by OA was reviewed as relevant to human exposure, regulatory activities, and risk management efforts occurring worldwide, particularly in Europe. OA moves through the food chain and has been found in the tissues and organs of animals, including human blood and breast milk. Results from the National Toxicology Program's rodent bioassays show significantly increased incidence of mammary gland tumors in female rats and kidney tumors in male and female rats given OA orally. Liver tumors in female mice fed OA in the diet have also been observed. In humans, OA exposure has been most often associated with the kidney disease Balkan endemic nephropathy (BEN), symptoms of which include tumors of the kidney and urinary tract. No epidemiological studies have yet adequately evaluated the cancer risk of OA in human populations. Studies have shown OA to be genotoxic as well as immunotoxic, although its mode of action is not fully understood. Organizations and agencies in many countries are currently promulgating standards for OA in foods and beverages. Increased efforts in farm management and food safety are being made to mitigate the risks to public health posed by OA. The U.S. Food and Drug Administration (FDA) is currently evaluating data on OA levels in domestic and imported commodities but has not established official regulations or guidelines for OA in the U.S. food supply.

Critical evaluation of the cancer risk of dibromochloropropane (DBCP).

Dibromochloropropane (1,2-dibromo-3-chloropropane, DBCP), a pesticide used widely for over 20 years to control nematodes on crops, turf and in nurseries, was banned by the United States Environmental Protection Agency (US EPA) in 1977 because of evidence of infertility in men and induction of a variety of tumors in laboratory animals. Despite the ban on the use of DBCP, this pesticide remains persistent in soil and continues to be detected as a groundwater contaminant in areas of past high use, in particular California's Central Valley. In this review, we present a critical evaluation of the available scientific literature on the potential for DBCP to affect cancer risk, including the results of animal cancer bioassays, human epidemiological studies and in vitro and in vivo genotoxicity studies. In addition, we provide updated information on DBCP chemistry and metabolism, production and past use, current regulations, its environmental fate, potential for human exposure and current remediation efforts. Results from long-term cancer bioassays in rodents show a statistically significant increase in the incidence of malignant and benign mammary gland tumors in female rats treated orally with DBCP compared to controls and some evidence of increased incidence of mammary fibroadenomas in DBCP low-dose treated female rats exposed by inhalation. Significantly increased incidence of tumors of the forestomach occurred in both sexes of rats and mice treated orally. Rats exposed to DBCP by inhalation showed significant increases in tumors of the tunica vaginalis in males; tumors of the pharynx and adrenal gland in females; and tumors of the tongue, nasal turbinate and nasal cavity in both sexes compared to controls. Male and female mice exposed to DBCP by inhalation experienced increased tumor incidence in the lungs and nasal cavity compared to controls. Significant increases in tumors of the lung and forestomach have also been reported in female mice treated by a dermal route. Although high mortality rates in both rat and mouse bioassays limited the ability to detect tumors late in life, the induction of a variety of tumors by multiple routes of exposure in two rodent species provides clear evidence of a DBCP tumorigenic response. In vitro, in vivo and human genotoxicity studies indicate that DBCP is capable of acting as a mutagen and clastogen. Few studies have been conducted to assess whether DBCP workplace or drinking water exposures affect cancer risk in humans. While case-control, cohort and ecological epidemiology studies have not found significant, positive associations between DBCP exposure and cancer in exposed populations, these studies have numerous limitations including small numbers of participants, a lack of control for confounding factors, lack of exposure information on DBCP and other chemicals and short follow-up times. Given the persistent nature of DBCP contamination in areas of past use, efforts should be made to continue remediation efforts and follow previously exposed populations for development of certain human cancers, including breast, ovarian, stomach, respiratory, oral and nasal cancers, among others.