Neuroembryopathic effect of trichloroacetic acid in rats exposed during organogenesis.
BACKGROUND
Halogenated hydrocarbons such as trichloroacetic acid (TCA) are among the most common water supply contaminants in the world. This study examines the effect of TCA on the developing brain of the Charles Foster rat.


METHODS
Adult pregnant rats were placed in the test group and exposed to various concentration of TCA (i.e., 1000, 1200, 1400, 1600, and 1800 mg/kg body weight [b.w.]) by oral gavage throughout the period of organogenesis from Gestation Day (GD) 6-15 of gestation. Trichloroacetic acid was administered in the form of trichloroacetate, which is reduced to TCA in the body. The control mother rats were administered an equal volume of distilled water. Fetal brains were examined for their external and histological malformation.


RESULTS
On GD 19, TCA administration led to an initial increase of brain weight at 1000 mg/kg b.w. and then a weight reduction after TCA doses of 1200 mg/kg b.w. and over. The brain of the formalin-fixed fetuses at 1000 and 1200 mg/kg b.w. showed hydrocephalus with breech of the ependymal lining, altered choroids plexus architecture, and increased apoptosis. At doses of 1400 mg/kg b.w. and above, the brain showed not only enhanced apoptosis of the neuronal cells, but extravasation of erythrocytes within the cortical parenchyma, vacuolation of the neuropil, and multiple cavity formation.


CONCLUSIONS
With an increase in dose of TCA i.e., 1200 mg/kg b.w. and above, there is enhanced apoptosis, leading to increased neuronal death, which consequently led to the reduction in the brain weight as compared to controls. The fetal central nervous system is susceptible to the toxic effect of TCA.
Singh
Royana
R
Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. singhroyana@rediffmail.com
D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced*; D008297:Male; D038081:Organogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014238:Trichloroacetic Acid / Q000008:administration & dosage / Q000633:toxicity*
D014238:Trichloroacetic Acid