Isocyanates and human health: multistakeholder information needs and research priorities.

OBJECTIVES: To outline the knowledge gaps and research priorities identified by a broad base of stakeholders involved in the planning and participation of an international conference and research agenda workshop on isocyanates and human health held in Potomac, Maryland, in April 2013. METHODS: A multimodal iterative approach was used for data collection including preconference surveys, review of a 2001 consensus conference on isocyanates, oral and poster presentations, focused break-out sessions, panel discussions, and postconference research agenda workshop. RESULTS: Participants included representatives of consumer and worker health, health professionals, regulatory agencies, academic and industry scientists, labor, and trade associations. CONCLUSIONS: Recommendations were summarized regarding knowledge gaps and research priorities in the following areas: worker and consumer exposures; toxicology, animal models, and biomarkers; human cancer risk; environmental exposure and monitoring; and respiratory epidemiology and disease, and occupational health surveillance.

Perfluoroalkyl acids: a review of monitoring and toxicological findings.

In recent years, human and wildlife monitoring studies have identified perfluoroalkyl acids (PFAA) worldwide. This has led to efforts to better understand the hazards that may be inherent in these compounds, as well as the global distribution of the PFAAs. Much attention has focused on understanding the toxicology of the two most widely known PFAAs, perfluorooctanoic acid, and perfluorooctane sulfate. More recently, research was extended to other PFAAs. There has been substantial progress in understanding additional aspects of the toxicology of these compounds, particularly related to the developmental toxicity, immunotoxicity, hepatotoxicity, and the potential modes of action. This review provides an overview of the recent advances in the toxicology and mode of action for PFAAs, and of the monitoring data now available for the environment, wildlife, and humans. Several avenues of research are proposed that would further our understanding of this class of compounds.

The applicability of biomonitoring data for perfluorooctanesulfonate to the environmental public health continuum.

Perfluorooctanesulfonate and its salts (PFOS) are derived from perfluorooctanesulfonyl fluoride, the basic chemical building block for many sulfonyl-based fluorochemicals used as surfactants and for their repellent properties. PFOS is highly persistent in the environment and has a long serum elimination half-life in both animals and humans. PFOS has been detected globally in the environment and in blood serum in various populations throughout the world, with the majority of human sampling done in the United States and Japan. The mechanisms and pathways leading to the presence of PFOS in human blood are not well characterized but likely involve both direct exposures to PFOS or chemicals and materials that can degrade to PFOS, either in the environment or from industrial and commercial uses. In 2000 the 3M Company, a major manufacturer, announced a phaseout of PFOS-related materials. Animal studies indicate that PFOS is well absorbed orally and distributes mainly in blood serum and the liver. Several repeat-dose toxicology studies in animals consistently demonstrated that the liver is the primary target organ. In addition there is a steep dose response for mortality in sexually mature rats and primates as well as in neonatal rats and mice exposed in utero. Several biomonitoring research needs that have been identified on PFOS include additional data from general populations pertaining to other matrices besides blood; matched serum and urine samples from humans and research animals; and comparison of whole blood, serum, and plasma concentrations from the same individuals.

Blood lead concentration and delayed puberty in girls.

BACKGROUND: Environmental lead exposure has been linked to alterations in growth and endocrine function. It is not known whether such exposure affects pubertal development. METHODS: We analyzed the relations between blood lead concentration and pubertal development among girls (defined as females 8 to 18 years of age) who were enrolled in a cross-sectional study (the third National Health and Nutrition Examination Survey) in which race was self-reported or proxy-reported: 600 were non-Hispanic white, 805 were non-Hispanic African-American, and 781 were Mexican-American girls. Puberty was measured on the basis of the age at menarche and Tanner stage for pubic-hair and breast development. RESULTS: Geometric mean lead concentrations were less than 3 microg per deciliter (0.144 micromol per liter) in all three groups. As compared with concentrations of 1 microg per deciliter (0.048 micromol per liter), lead concentrations of 3 microg per deciliter were associated with decreased height (P<0.001), after adjustment for age, race, and other factors, but not with body-mass index or weight. Blood lead concentrations of 3 microg per deciliter were associated with significant delays in breast and pubic-hair development in African-American and Mexican-American girls. The delays were most marked among African-American girls; in this group, the delays in reaching Tanner stages 2, 3, 4, and 5 associated with a lead concentration of 3 microg per deciliter as compared with 1 microg per deciliter were 3.8, 5.3, 5.8, and 2.1 months, respectively, for breast development and 4.0, 5.5, 6.0, and 2.2 months, respectively, for pubic-hair development; the associated delay in age at menarche was 3.6 months. In white girls, there were nonsignificant delays in all pubertal measures in association with a lead concentration of 3 microg per deciliter. CONCLUSIONS: These data suggest that environmental exposure to lead may delay growth and pubertal development in girls, although confirmation is warranted in prospective studies.