First Detection of Photoinitiators and Metabolites in Human Sera from United States Donors

Photoinitiators (PIs), including benzophenones (BZPs), thioxanthones (TXs), and amine co-initiators (ACIs), are commonly used in photopolymerization systems, and their contamination in foodstuffs and the environment is attracting attention. Although humans are likely exposed to PIs, no data on human burdens of these chemicals are available. In this study, 18 PIs were detected in 50 individual human serum samples with concentrations of Sigma PIs (sum of the detected PIs) from 423 to 2870 pg/mL (geometric mean, GM: 836 pg/mL). Sigma BZPs (231-1240 ng/g,; GM: 593 pg/mL) were the dominant components, while Sigma TXs (21.0-1431 ng/g; GM: 145 pg/mL) and Sigma ACIs (11.3-976 ng/g; GM: 48.5 pg/mL) were much lower. Data analysis found significantly higher concentrations of most PIs in the male sera than in the female (p < 0.05). Sigma PIs (2921-4139 ng/g; GM: 3621 pg/mL) were also detected in five pooled serum samples, each from at least 1000 donors, indicating the prevalent human burdens of PIs in a large population. Human liver S9 biodegradations of representative PIs, 2-isopropylthioxanthone (2-ITX) and 2,4-diethylthioxanthone (DETX), were conducted. Hydroxylation, sulfoxide, and sulfone metabolites of DETX and 2-ITX were identified by high resolution mass spectrometry in human liver S9 incubation systems. With synthesized standards, the sulfoxide and sulfone metabolites were successfully detected in the human serum samples, which contributed substantially to total human burdens. The ubiquitous presence of PIs in human sera indicates significant human exposure to PIs, although photopolymerization reaction has been generally considered a green technology.