Specific accumulation and elimination kinetics of tris(4-chlorophenyl)methane, tris(4-chlorophenyl)methanol, and other persistent organochlorines in humans from Japan.

Abstract

We examined human adipose tissue, liver, and bile from humans in Japan to understand the contamination status, specific accumulation, and elimination of two newly identified environmental contaminants, tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and other persistent organochlorines such as polychlorinated biphenyls (PCBs), DDT and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and chlordane compounds (CHLs). TCPMe and TCPMOH concentrations in Japanese human adipose tissue were slightly higher than those reported previously, indicating widespread exposure to these compounds in humans. Elevated residues of PCBs and DDTs are found in adipose tissue and liver. Concentrations in bile strongly correlated with concentrations in adipose fat and liver, which may suggest an equilibration in adipose fat/bile and liver/bile and possible biliary excretion of persistent organochlorines in humans. Composition of the organochlorines accumulated further indicates a metabolic capacity in humans higher than that of marine mammals. We observed age-dependent accumulation for TCPMe, TCPMOH, and other organochlorines, but there were no significant gender differences. p,p'-DDE and TCPMe were estimated to have low biliary excretion rate. Elimination potential of persistent organochlorines may be related to their octanol-water partition coefficient. The relationship between excretion rate and octanol-water partition coefficient may be used to predict the biliary excretion potential of some other lipophilic organochlorines such as dioxins and dibenzofurans in humans. The presence of organochlorines in bile suggests that the hepatic excretory system plays a major role in the elimination of xenobiotics in humans. To our knowledge, this is the first study of accumulation and elimination of TCPMe and TCPMOH in humans.

Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly obese patients: a cohort study

“…Regarding excretion, the presence of POPs in human bile from autopsy samples with significant relationship to concentrations in blood, adipose fat and liver indicates biliary excretion of POPs [ 46 , 47 ]. NASH patients generally have increased levels of bile acids in both plasma and liver tissue [ 48 , 49 ] and an increase of serum bile acids in NASH as compared to less severe stages of NAFLD has been found in obese patients undergoing bariatric surgery [ 50 ].…”

Profiles of polychlorinated biphenyl congeners, organochlorine pesticides, and butyltins in southern sea otters and their prey

“…Lipid-normalized concentrations of TCPMOH in sea otter livers (100 ng/g) were approximately ninefold greater than concentrations found in prey items (11 ng/g), suggesting biomagnification of this compound in the sea otter food chain. Earlier studies have also reported the biomagnification of TCPMOH in humans and marine wildlife [18,19]. Nevertheless, concentrations of TCPMOH in sea otter livers were lower than those found in livers of California sea lions from central California [20].…”

Tris(4‐chlorophenyl)methane and tris(4‐chlorophenyl)methanol disrupt pancreatic organogenesis and gene expression in zebrafish embryos

“…These concentrations of TCPM and TCPMOH were selected because they were less than half of the NOAEL concentrations for survival and deformities in zebrafish embryos (Navarrete et al, 2021;Yost et al, 2022). It is important to note that transplacental transfer of TCPMOH (3.3%-5.3%) and TCPM (0.55%-1.2%) has been confirmed in whales (Kajiwara, Kamikawa, et al, 2008) and maternal transfer of TCPMOH has been observed during lactation in seals (Kajiwara, Watanabe, et al, 2008) and humans (Minh et al, 2001). Therefore, direct transplacental perfusion of the fetus and oral exposure in infants is likely.…”