Bioconcentration and Metabolism of Pyriproxyfen in Tadpoles of African Clawed Frogs, Xenopus laevis

Abstract

Bioconcentration and metabolism of pyriproxyfen uniformly labeled with C at the phenoxyphenyl ring were studied using tadpoles of African clawed frog, Xenopus laevis, exposed to water at the nominal concentrations of 3 and 300 ppb for 22 days under the flow-through conditions, with a following 3 day depuration phase. Neither meaningful mortality nor abnormal behavior was observed in control and exposure groups throughout the study. After the rapid uptake to tadpoles, pyriproxyfen was extensively metabolized and excreted, and as a result, steady-state bioconcentration factors and depuration half-lives ranged from 550 to 610 and from 0.34 to 0.54 days, respectively. The metabolites were mostly distributed in the liver or gastrointestinal tract. The major metabolic reactions were hydroxylation at the 4' position of the phenoxyphenyl group and cleavage of the ether linkage, followed by sulfate conjugation.

A microarray‐based comparative analysis of gene expression profiles in thyroid glands in amphibian metamorphosis: differences in effects between chemical exposure and food restriction

“…In the PYR exposure groups, the sublethal effects were confirmed to be the same as in previous studies (Ose et al, 2017;US EPA, 2015), as delayed development based on decreases in NF stage, HLL/SVL and BW with a reduction of food consumption without histopathological changes, likely to originate from systemic toxic effects (Figures 1, 2 and 3). On the other hand, PTU exposure resulted in delayed development of tadpoles based on decreases in NF stage, HLL/SVL and SVL with apparent histopathological changes in the thyroid glands as previously reported (Degitz et al, 2005;Miyata & Ose, 2012a, 2012bOpitz et al, 2005).…”

“…As reduced food consumption with so much leftover feed was observed, and as there were no histopathological changes in the thyroid glands, the delayed development was considered caused by deteriorating condition due to nutritional deficiency, concluding that the PYR has no potential for endocrine‐disrupting effects on the HPT axis. The delayed development along with so much leftover feed by the PYR exposure to tadpoles of X. laevis during metamorphosis was reproduced in our previous study (Ose, Miyamoto, Fujisawa, & Katagi, ).…”

ZIKA virus effects on neuroprogenitors are exacerbated by the main pyriproxyfen metabolite via thyroid hormone signaling disruption

“…The WHO recommended that daily intake of PPF should not exceed 0.3 mg/L for an average adult, and advised that the concentration of PPF in drinking water containers should be lower than 0.01 mg/L (13). The main pathway of PPF metabolism is hydroxylation at the 4'-position, producing principally 4'-OH-PPF in both vertebrates and invertebrates (13,(21)(22)(23). PPF is documented to be rapidly taken up and metabolized, resulting in low bio-concentrations of the parent compound circulating in the organism (21).…”

“…The main pathway of PPF metabolism is hydroxylation at the 4'-position, producing principally 4'-OH-PPF in both vertebrates and invertebrates (13,(21)(22)(23). PPF is documented to be rapidly taken up and metabolized, resulting in low bio-concentrations of the parent compound circulating in the organism (21). We therefore hypothesized that 4'-OH-PPF rather than PPF could be the main compound acting in vivo.…”

The pyriproxyfen metabolite 4'OH- pyriproxyfen disrupts thyroid hormone signaling and enhances Musashi-1 levels in neuroprogenitors.

“…The major pathway of PPF metabolism is hydroxylation at the 4’-position, producing majoritarily 4’-OH-PPF in Xenopus, mice, rats, goats, house flies and chicken (Fujimori, 1999; Ose et al, 2017; Yoshino et al, 1995; Zhang et al, 1998). To our knowledge, no studies have yet assessed the toxicological potential of 4’-OH-PPF.…”