Quaternary ammonium compounds (QACs) are common substances utilized in cleaners, ophthalmic solutions, swimming pool treatments, cosmetics, and other consumer goods. Previous studies have shown that QAC exposure causes infertility in both male and female mice. Based on these studies, we hypothesized that oral QAC exposure negatively impacts male and female reproduction through changes in physiologic and endocrine mechanisms rather than direct toxicity to gametes. Endocrine disruption was assessed by evaluating luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in male and female mice exposed orally throughout gestation and lactation, and by changes in estrogen and progesterone in in orally exposed females throughout pregnancy. Sperm functionality and spermatogenesis were assessed by in vitro fertilization; while Sertoli cell homeostasis was evaluated by determining cellular metabolism, cell cycle progression and blood-testes barrier (BTB) permeability. QAC exposure decreased LH, and FSH concentrations in both males and females, and decreased progesterone and estrogen concentrations during pregnancy. QACs significantly decreased Sertoli cell metabolism at 0.0005% ADBAC+DDAC well before disruption of the BTB at 0.01%. Fertilization was not affected 24h after exposure but was decreased after a 10 day rest period suggesting a disruption in spermatogenesis rather than direct toxicity to sperm. Lastly, QAC exposure altered Sertoli cell cycling with a G2/M cycle arrest. While the effect of QAC exposure on humans is unknown, implications from the in vivo and in vitro studies are concerning given the rise in infertility rates and increased reliance on assisted reproductive technologies along with ubiquitous exposure to QACs.

Use of personal care products and household and commercial cleaners with antibacterial capabilities has increased human exposure to an array of chemicals. Because these products are washed down the drain, they are discharged with wastewater into fields, lakes, streams, oceans, and municipal water systems. This chapter focuses on the uses, persistence, routes of human exposure, and potential health effects of four common environmental chemicals or chemical classes—parabens, triclosan, triclocarban, and quaternary ammonium compounds—because exposure to them is ubiquitous, environmental contamination is significant, and evidence of harm has emerged. These man-made environmental contaminants illustrate how the rapid introduction of new chemicals into consumer products must be weighed against the unavoidable environmental contamination and potential biologic effects that may ensue.

Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common ingredients in household bathroom and kitchen cleaning sprays. ADBAC + DDAC cause reproductive toxicity in mice. The aim of the present study was to investigate gender-specific reproductive effects from ADBAC + DDAC. Female reproduction was assessed through ovulation, oocyte implantation, and estrus cycling. Male reproductive function was assessed by sperm concentration, motility, and viability. Numbers of corpora lutea were not different after 2 weeks, but decreased after 8 weeks of ADBAC + DDAC exposure. Dams exposed for 5 weeks to ADBAC + DDAC spent significantly less time in estrus. ADBAC + DDAC exposed males exhibited declines in both sperm concentration and motility, but not sperm viability. Subfertility in mice from ADBAC + DDAC exposure is, therefore, mediated through reproductive disturbances in both females and males. While the effect of ADBAC + DDAC exposure on human health is unclear, widespread exposure necessitates further consideration of their potential reproductive toxicity.

Disinfection by-products (DBPs) arise when natural organic matter in source water reacts with disinfectants used in the water treatment process. Studies have suggested an association between DBPs and birth defects. Neural tube defects (NTDs) in embryos of untreated control mice were first observed in-house in May 2006 and have continued to date. The source of the NTD-inducing agent was previously determined to be a component of drinking water. Tap water samples from a variety of sources were analyzed for trihalomethanes (THMs) to determine if they were causing the malformations. NTDs were observed in CD-1 mice provided with treated and untreated surface water. Occurrence of NTDs varied by water source and treatment regimens. THMs were detected in tap water derived from surface water but not detected in tap water derived from a groundwater source. THMs were absent in untreated river water and laboratory purified waters, yet the percentage of NTDs in untreated river water were similar to the treated water counterpart. These findings indicate that THMs were not the primary cause of NTDs in the mice since the occurrence of NTDs was unrelated to drinking water disinfection.

Quaternary ammonium compounds (QACs) are antimicrobial disinfectants commonly used in commercial and household settings. Extensive use of QACs results in ubiquitous human exposure, yet reproductive toxicity has not been evaluated. Decreased reproductive performance in laboratory mice coincided with the introduction of a disinfectant containing both alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC). QACs were detected in caging material over a period of several months following cessation of disinfectant use. Breeding pairs exposed for six months to a QAC disinfectant exhibited decreases in fertility and fecundity: increased time to first litter, longer pregnancy intervals, fewer pups per litter and fewer pregnancies. Significant morbidity in near term dams was also observed. In summary, exposure to a common QAC disinfectant mixture significantly impaired reproductive health in mice. This study illustrates the importance of assessing mixture toxicity of commonly used products whose components have only been evaluated individually.

In May of 2006, our lab suddenly began to observe neural tube defects (NTDs) in embryos of untreated control mice. Exposure to a teratogenic agent in tap water was identified as the cause. Pharmaceuticals have emerged as ubiquitous contaminants of drinking water. One such NTD inducing drug, carbamazepine (CBZ), was analyzed. CBZ was detected in several ground, surface, and tap waters, ranging in concentrations from 0.28 ng/L to 9.5 ng/L. To test whether CBZ was responsible for NTDs, we exposed mice to CBZ in 2 water types. In well water, CBZ concentrations were at 15 and 1500 ng/L. In double distilled water, CBZ concentrations were at 6 and 1500 ng/L. Both studies found no significant differences in NTD rates among the dose groups. As no dose effect was observed, we concluded that CBZ was not directly responsible for the malformations; however it is possible a mixture of contaminants, including CBZ, may be involved.Grant Funding Source : NIH‐NIHSR21E5016886‐01

Neural tube defects (NTDs) are a common birth defect responsible for spina bifida and anencephaly. They are caused by genetic and environmental factors, including vitamin deficiencies, pollutants, and pharmaceuticals. In May of 2006, NTDs were observed in untreated control mice. The cause was traced to the drinking water provided to the mice. We investigated possible sources of the teratogen to narrow the potential list of contaminants. To determine if the teratogen formed in the water bottles as a result of bacterial metabolism, we compared NTD rates in mice provided sterilized water daily with mice receiving weekly water changes. NTD rates were not significantly different between the daily (17.4%) and the weekly (19.5%) groups. Thus, the teratogen is not likely caused by bacterial metabolism in the mouse's water bottle. To determine where the teratogen might enter the water supply; we compared NTD rates in mice provided water from 5 locations along the watercourse supplying water to the treatment plant. The stream begins in unpopulated National Forest land and runs through both rural and urban areas. We found no significant difference in NTD rates in mice provided water from the 5 locations, with rates ranging from 16 – 27%. From this, it appears that the teratogen is widely distributed in the environment. This work was funded by the VA‐MD College of Veterinary Medicine and NIH‐NIEHS R21ES016886.

Land use change is one of the most commonly cited contributing factors to infectious disease emergence, yet the mechanisms responsible for such changes and the spatial scales at which they operate are rarely identified. The distributions of parasites with complex life cycles depend on interactions between multiple host species, suggesting the net effects of land use on infection patterns may be difficult to predict a priori. Here, we used an information-theoretic approach to evaluate the importance of land use and spatial scale (local, watershed, and regional) in determining the presence and abundance of multi-host trematodes of amphibians. Among 40 wetlands and 160 hosts sampled, trematode abundance, species richness, and the presence and abundance of pathogenic species were strongly influenced by variables at the watershed and regional scales. Based on model averaging results, overall parasite richness and abundance were higher in forested wetlands than in agricultural areas; however, this pattern was influenced by a wetland's proximity to the Mississippi Flyway at the regional scale. These patterns likely reflect the activity of trematode definitive hosts, such as mammals and especially birds, such that infections decreased with increasing distance from the Mississippi River. Interestingly, despite lower mean infections, agricultural wetlands had higher variances and maximum infections. At the wetland scale, phosphorus concentrations and the abundances of intermediate hosts, such as snails and larval amphibians, positively affected parasite distributions. Taken together, these results contribute to our understanding of how altered landscapes affect parasite communities and inform further research on the environmental drivers of amphibian parasite infections.