Prenatal toxicity and maternal-fetal distribution of 1,3,5,8-tetrachloronaphthalene (1,3,5,8-TeCN) in Wistar rats

Chemosphere. 2019 Jul:226:75-84. doi: 10.1016/j.chemosphere.2019.03.107. Epub 2019 Mar 19.

Abstract

1,3,5,8-tetrachloronaphthalene (1,3,5,8-TeCN) is a Persistent Organic Pollutant (POP) that belongs to the group of polychlorinated naphthalenes (PCNs). The aim of the study was to investigate the maternal-fetal distribution and prenatal toxicity of 1,3,5,8-TeCN after its administration to pregnant Wistar rats during organogenesis. Radiolabeled 1,3,5,8-tetrachloronaphthalene-[ring-U-3H] was given by gavage at a dose of 0.3 mg per dam to evaluate its tissue distribution, and that of unlabeled 1,3,5,8-TeCN, at daily doses of 0.3, 1.0 or 3.0 mg kg b.w.-1 to assess prenatal toxicity. After a single administration of 1,3,5,8-TeCN, the highest concentration was detected in maternal adipose tissue. The concentration in the brain, uterus, kidneys, adrenals, ovaries, lungs and liver established in dams were two to nine times higher than in the maternal blood. 1,3,5,8-TeCN penetrated the blood-brain-barrier and the placenta. The results obtained from developmental toxicity indicate that 1,3,5,8-TeCN did not cause maternal toxicity and was not embryotoxic or teratogenic. However, fetotoxic effects were observed after non-toxic doses for dams (1.0 and 3.0 mg∙b.w.-1·day-1). 1,3,5,8-TeCN did not induce congenital skeletal defects but increased the number of fetuses with sternum ossification delay. After a dose of 3.0 mg kg b.w.-1·day-1, significantly more fetuses were found with enlargement of the renal pelvis: unilateral in female offspring and bilateral in male offspring. At the doses used, 1,3,5,8-TeCN, unlike hexachloronaphthalene, was not a CYP1A1 inducer.

Keywords: 1,3,5,8-tetrachloronaphthalene; Developmental toxicity; Fetotoxicity; Maternal-fetal transfer; Rat.

MeSH terms

  • Animals
  • Female
  • Fetus / drug effects*
  • Male
  • Naphthalenes / toxicity*
  • Placenta / drug effects
  • Pregnancy
  • Rats
  • Rats, Wistar

Substances

  • Naphthalenes
  • 1,2,3,4,5,6-hexachloronaphthalene