Examination of generational impacts of adolescent chemotherapy: Ifosfamide and potential for epigenetic transgenerational inheritance.

The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Pathologies such as delayed pubertal onset, kidney disease, and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) in chemotherapy lineage sperm in the F1 and F2 generations were identified. Therefore, chemotherapy exposure impacts pathology susceptibility in subsequent generations. Observations highlight the importance that prior to chemotherapy, individuals need to consider cryopreservation of germ cells as a precautionary measure if they have children.

Environmental epigenetics and epigenetic inheritance in domestic farm animals.

Epigenetics refers to molecular factors and processes around DNA that can affect genome activity and gene expression independent of DNA sequence. Epigenetic mechanisms drive developmental processes and have also been shown to be tied to disease development. Many epigenetic studies have been done using plants, rodent, and human models, but fewer have focused on domestic livestock species. The goal of this review is to present current epigenetic findings in livestock species (cattle, pigs, sheep and poultry). Much of this research examined epigenetic effects following exposure to toxicants, nutritional changes or infectious disease in those animals directly exposed, or in the offspring they produced. A limited number of studies in domestic animals have examined epigenetic transgenerational inheritance in the absence of continued exposures. One example used a porcine model to investigate the effect that feeding males a diet supplemented with micronutrients had on liver DNA methylation and muscle mass in grand-offspring (the transgenerational F2 generation). Further research into how epigenetic mechanisms affect the health and production traits of domestic livestock and their offspring is important to elucidate.

Ecological risk assessment for mink and short-tailed shrew exposed to PCBs, dioxins, and furans in the Housatonic River area.

A probabilistic risk assessment was conducted to characterize risks to a representative piscivorous mammal (mink, Mustela vison) and a representative carnivorous mammal (short-tailed shrew, Blarina brevicauda) exposed to PCBs, dioxins, and furans in the Housatonic River area downstream of the General Electric (GE) facility in Pittsfield, Massachusetts. Contaminant exposure was estimated using a probabilistic total daily intake model and parameterized using life history information of each species and concentrations of PCBs, dioxins, and furans in prey collected in the Housatonic River study area. The effects assessment preferentially relied on dose-response curves but defaulted to benchmarks or other estimates of effect when there were insufficient toxicity data. The risk characterization used a weight of evidence approach. Up to 3 lines of evidence were used to estimate risks to the selected mammal species: 1) probabilistic exposure and effects modeling, 2) field surveys, and 3) species-specific feeding or field studies. The weight of evidence assessment indicated a high risk for mink and an intermediate risk for short-tailed shrew.

Refined avian risk assessment for aldicarb in the United States.

Aldicarb was recently reviewed by the US Environmental Protection Agency (USEPA) for re-registration eligibility. In this paper, we describe a refined avian risk assessment for aldicarb that was conducted to build upon the screening-level methods used by USEPA. The goal of the refined ERA was to characterize and understand better the risks posed by aldicarb to birds in areas where the pesticide is applied. Aldicarb is a systemic insecticide sold in granular form under the trade name Temik. It is applied directly to soil and is used to control mites, nematodes, and aphids on a variety of crops (e.g., cotton, potatoes, peanuts). Consumption of grit is necessary for proper digestion in many bird species, particularly for granivores and insectivores. Thus, aldicarb granules may be mistaken for grit by birds. The Granular Pesticide Avian Risk Assessment Model (GranPARAM) is described in a companion paper and was used to estimate the probability and magnitude of effects to flocks of birds that frequent aldicarb-treated fields. One hundred thirty-five exposure scenarios were modeled that together include a range of bird species, crops, application methods and rates, and regions in the United States. The results indicated that, even for the most sensitive bird species, the risks associated with the agricultural use of granular aldicarb are negligible to low. There are several reasons for the limited risk: 1) the Temik formulation includes a gypsum core and a graphite coating and is black in color, all of which have been shown to be unattractive to birds, and 2) the pesticide is applied subsurface and rapidly dissolves following contact with water. The fact that no bird kill incidents involving appropriate label uses of aldicarb have been conclusively documented in the United States over its 38 years of use supports the results of this refined risk assessment.

Refined aquatic risk assessment for aldicarb in the United States.

Aldicarb is a systemic insecticide applied directly to soil and to control mites, nematodes, and aphids on a variety of crops (e.g., cotton, potatoes, peanuts). It is highly soluble in water (6,000 mg/L) and mobile in soils (K(oc) = 100). As a result, aldicarb has the potential to be transported to aquatic systems close to treated fields. The US Environmental Protection Agency (USEPA) recently conducted an aquatic screening-level ERA for aldicarb as part of the re-registration review process. We conducted a refined risk assessment for aldicarb to characterize better the risks posed by aldicarb to fish and invertebrates inhabiting small freshwater ponds near agricultural areas. For the exposure assessment, tier II PRZM/EXAMS (Predicted Root Zone Model [PRZM] and Exposure Analysis Modelling System [EXAMS]) modelling was conducted to estimate 30-y distributions of peak concentrations of aldicarb and the carbamate metabolites (aldicarb sulfoxide, aldicarb sulfone) in surface waters of a standard pond arising from different uses of aldicarb. The effects assessment was performed using a species sensitivity distribution (SSD) approach. The resulting risk curves as well as available incident reports suggest that risks to freshwater fish and invertebrates from exposure to aldicarb are minor. The available monitoring data did not provide conclusive evidence about risks to aquatic biota.