Trichloroacetic Acid Accumulates in Murine Amniotic Fluid after Tri‐ and Tetrachloroethylene Inhalation

Abstract

The distribution of trichloroethylene (Tri) and tetrachloroethylene (Tetra) and their metabolites have been studied in pregnant mice by means of whole‐body autoradiography (14C‐labelled Tri and Tetra) and gas chromatography, with special emphasis on possible uptake and retention in the foetoplacental unit. Volatile (non‐metabolized) activity appeared at short intervals after a 10 min. or 1 hr inhalation period in foetus and amniotic fluid. Most notable, however, was a strong accumulation and retention (peak at 4 hrs) in amniotic fluid of the metabolite trichloroacetic acid (TCA) after inhalation of either of the solvents. The main metabolite of Tri, trichloroethanol (TCE) (or conjugates), did not accumulate specifically as compared to maternal plasma. TCA infused intravenously in the maternal plasma was accumulated in amniotic fluid, but less pronounced than after Tri and Tetra inhalation, indicating that some metabolism of Tri and Tetra to TCA may occur in the foetoplacental unit. The results suggest that TCA may be transported to the foetus partly paraplacentally through foetal membranes and amniotic fluid, with the possibility of foetal swallowing or absorption through the skin. Foetal urinary activity also suggests that circulation between foetus and amniotic fluid may contribute to the long‐term retention in the foetoplacental unit. In the mother, after inhalation exposures, and in intraperitoneally injected newborn mice, non‐extractable radioactivity was found in the respiratory tract, liver, and kidney, indicating binding to these organs through metabolism.

Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the cape cod health study: A retrospective cohort study

“…Neuroendocrine toxicity is plausible following prenatal and childhood exposure because PCE can cross the placenta in animals [5] and is present in human breast milk among women with and without occupational exposure [6, 7]. …”

“…There is a paucity of literature on PCE and reproductive physiology. Tri- and tetrachloroethylene are noted to cross the placenta after inhalational exposure in a murine model [5]. Other organic solvents, such as chlorinated hydrocarbons are secreted into breastmilk among women with and without occupational exposure [6, 7], and benzene is detectable in the follicular fluid surrounding the oocyte among in vitro fertilization (IVF) patients at the time of egg retrieval [8].…”

Early lifestage exposure and potential developmental susceptibility to tetrachloroethylene

“…Due to its high lipophilicity, perc has been found to distribute widely to all tissues in the body as observed in early lifestages of humans (Gaillard et al, 1995;Garnier et al, 1996;Kö ppel et al, 1985) and early lifestages of animals (Dallas et al, 1994;Ghantous et al, 1986;Savolainen et al, 1977;Schumann et al, 1980;Szakmáry et al, 1997), although this is true for adults as well. It should be noted that the total body burden of perc increases with age (Clewell et al 2004), as would be expected, given that adult body weight is generally positively correlated with age.…”

“…Perc and its metabolites have been measured in the fetus and amniotic fluid in rodents after maternal inhalation. In rats after one hour of exposure, perc was measured in amniotic fluid, showing a decrease over the course of 24 hours, whereas the metabolite trichloroacetic acid (TCA) peaked 4 hours after exposure in the fetus and amniotic fluid (Ghantous et al, 1986). After exposure to 1,500 mg/m 3 , levels in fetal blood were measured at 11.971.3 ml/ml, and in amniotic fluid at 5.971.3 ml/ml; after exposure to 8,500 mg/m 3 , levels in fetal blood were measured at 25.2.972.5 ml/ml, and in amniotic fluid at 17.9710.3 ml/ml (Szakmáry et al, 1997).…”

Trichloroethylene Alters Central and Peripheral Immune Function in Autoimmune-Prone MRL+/+Mice Following Continuous Developmental and Early Life Exposure

“…Earlier work in our laboratory provided the first experimental evidence that exposure to these doses of TCE in adult mice promoted CD4 + T-lymphocyte activation and autoimmunity. TCE easily crosses the placenta (Ghantous et al, 1986) and enters the maternal milk (Fisher et al, 1990). Thus, it was hypothesized that TCE may also affect the developing immune system of the offspring.…”