Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2019
2019
2019
BACKGROUND
Identification of female reproductive toxicants is currently based largely on integrated epidemiological and toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking.
OBJECTIVE
We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification.
METHODS
A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell–cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo--dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics.
DISCUSSION
Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.
View on PubMed2019
2019
2019
2019
2019
OBJECTIVE
Waterpipe tobacco (WPT; hookah) use is common in pregnant and reproductive-age women. Sweet flavours contribute to the appeal of WPT and are a potential regulatory target. This study investigated use, preferences and perceptions of WPT flavours in pregnant WPT users, and the impact of flavour preferences on preconception/prenatal WPT use and exposure biomarkers.
METHODS
58 pregnant WPT users (mean age=27 years) completed a detailed interview regarding their WPT flavours use, preferences and perceptions. Biomarkers of nicotine and carcinogen exposure (eg, cotinine, benzene, butadiene) were also collected.
RESULTS
55% of participants were dual/poly WPT users (ie, reported use of one or more other tobacco products in addition to WPT). Pregnant WPT users reported nearly exclusive use of flavoured WPT, with greater use of menthol/mint (68%) followed by fruit flavours (48%) (p<0.001), and greater preferences for fruit followed by menthol/mint flavours (ps<0.05). Harm perceptions did not differ among flavours. Compared with dual/poly WPT users, WPT-only users reported more total WPT use events, greater use of and preference for menthol/mint flavoured WPT (ps<0.001), and decreased exposure biomarkers (ps≤0.040). Preference for menthol/mint and fruit flavours predicted more flavoured WPT use events during preconception and pregnancy; preference for menthol/mint predicted detectable cotinine and benzene levels but not butadiene.
CONCLUSIONS
This is the first study of WPT flavour use, preferences and perceptions in pregnant women. Use of and preference for menthol/mint and fruit WPT flavours in this vulnerable population could be considered in regulating WPT flavours to protect the health of women and children.
View on PubMed2019