Improving the risk assessment of lipophilic persistent environmental chemicals in breast milk.

Lipophilic persistent environmental chemicals (LPECs) have the potential to accumulate within a woman's body lipids over the course of many years prior to pregnancy, to partition into human milk, and to transfer to infants upon breastfeeding. As a result of this accumulation and partitioning, a breastfeeding infant's intake of these LPECs may be much greater than his/her mother's average daily exposure. Because the developmental period sets the stage for lifelong health, it is important to be able to accurately assess chemical exposures in early life. In many cases, current human health risk assessment methods do not account for differences between maternal and infant exposures to LPECs or for lifestage-specific effects of exposure to these chemicals. Because of their persistence and accumulation in body lipids and partitioning into breast milk, LPECs present unique challenges for each component of the human health risk assessment process, including hazard identification, dose-response assessment, and exposure assessment. Specific biological modeling approaches are available to support both dose-response and exposure assessment for lactational exposures to LPECs. Yet, lack of data limits the application of these approaches. The goal of this review is to outline the available approaches and to identify key issues that, if addressed, could improve efforts to apply these approaches to risk assessment of lactational exposure to these chemicals.

Toxicological effects of the aquatic herbicide, fluridone, on male water mites (Hydrachnidiae: Arrenurus: Megaluracarus).

The acute toxicities for technical grade fluridone (Sonar™) and the commercial formulation of fluridone (Sonar®AS) were assessed for male water mites (Hydrachnidiae: Arrenurus: Megaluracarus). Signs of toxicity were evaluated by detection of locomotor dysfunction or death after exposure to concentrations of 100,000, 10,000, 1,000, and 100 µg/L of Sonar™ and 10,000, 5,000, 1,000, 100, and 10 µg/L of Sonar®AS in US EPA, moderately hard reconstituted water (MHRW). The median effective concentration (EC50) was 891 and 631 µg/L for Sonar™ at 48 and 96 h and less than 10 µg/L for Sonar®AS at 96 h. Increased duration of exposure to Sonar®AS from 48 to 96 h had a significant effect on increasing the rate of combined morbidity and mortality. At the lowest concentration of Sonar®AS tested, which is half the concentration allowed within 400 m of any functioning potable water intake for human usage, 40% of the mites were adversely affected at 48 h and 70% were affected after 96 h of exposure. This study demonstrates that Sonar®AS is 60-fold more toxic to water mites than the active ingredient alone. At currently acceptable application rates of 90-150 µg/L fluridone, the addition of ingredients classified as inert, as in Sonar®AS, result in an increased risk of adverse effects on populations of male water mites (Arrenurus: Megaluracarus) in aquatic ecosystems.

Saw palmetto extract induces nuclear heterogeneity in mice.

Saw palmetto (SW), a phytotherapeutic compound used in the treatment of prostate disease, was examined for potential nuclear effects. SW extract was incorporated into a complete casein-based semisynthetic rodent chow at 0%, 0.1% and 1% SW. SW was fed to mice for 6 weeks, after which the mice received a single i/p injection of either the known genotoxic agent methyl methanesulfonate (MMS) in saline or just saline. Forty-eight hours after injection, blood and bone marrow were collected for flow cytometric analysis. A significant effect of MMS was observed in both male and female mice with respect to: an increase in nuclear heterogeneity in bone marrow cells as measured by the coefficient of variation of the G1 peak in a flow histogram (6.32 versus 4.8 in male mice, 7.0 versus 4.9 in female mice) and an increase in the number of micronucleated blood cells (3.4% versus 0.56% male mice, 3.1% versus 0.6 in female mice) indicating a positive genotoxic response. SW also appears to increase the heterogeneity of bone marrow nuclei in a dose dependent manner (0-5.1%, 0.1-5.5% and 1-5.7% in male mice, 0-5.7%, 0.1-6.0% and 1-6.2% in female mice) without a concomitant increase in blood cell micronuclei. These results indicate that SW is not genotoxic with respect to physical DNA damage and that the changes observed in the bone marrow are due to chromatin conformation modifications in the nuclei of in vivo treated mouse cells.