Acute, Short-Term, and Subchronic Oral Toxicity of 1,1,1-Trichloroethane in Rats

Abstract

1,1,1-Trichloroethane (TRI) is a widely used solvent that has become a frequent contaminant of drinking water supplies in the U.S. There is very little information available on the potential for oral TRI to damage the liver or to alter its P450 metabolic capacity. Thus, a major objective of this investigation was to assess the acute, short-term, and subchronic hepatotoxicity of oral TRI. In the acute study, male Sprague-Dawley (S-D) rats were gavaged with 0, 0.5, 1, 2, or 4 g TRI/kg bw and killed 24 h later. No acute effects were apparent other than CNS depression. Other male S-D rats received 0, 0.5, 5, or 10 g TRI/kg po once daily for 5 consecutive days, rested for 2 days, and were dosed for 4 additional days. Groups of the animals were sacrificed for evaluation of hepatotoxicity 1, 5, and 12 days after initiation of the short-term experiment. This dosage regimen caused numerous fatalities at 5 and 10 g/kg, but no increases in serum enzymes or histopathological changes in the liver. For the subchronic study, male S-D rats were gavaged 5 times weekly with 0, 0.5, 2.5, or 5.0 g TRI/kg for 50 days. The 0 and 0.5 g/kg groups were dosed for 13 weeks. A substantial number of rats receiving 2.5 and 5.0 g/kg died, apparently due to effects of repeated, protracted CNS depression. There was evidence of slight hepatocytotoxicity at 10 g/kg, but no progression of injury nor appearance of adverse effects were seen during acute or short-term exposure. Ingestion of 0.5 g/kg over 13 weeks did not cause apparent CNS depression, body or organ weight changes, clinical chemistry abnormalities, histopathological changes in the liver, or fatalities. Additional experiments did reveal that 0.5 g/kg and higher doses induced hepatic microsomal cytochrome P450IIE1 (CYP2E1) in a dose- and time-dependent manner. Induction of CYP2E1 activity occurred sooner, but was of shorter duration than CYP2B1/2 induction. CYP1A1 activity was not enhanced. In summary, 0.5 g/kg po was the acute, short-term, and subchronic NOAEL for TRI, for effects other than transient CYP2E1 induction, under the conditions of this investigation. Oral TRI appears to have very limited capacity to induce P450s or to cause liver injury in male S-D rats, even when administered repeatedly by gavage in near-lethal or lethal dosages under conditions intended to maximize hepatic effects.

Oxidative Stress Mediated Cytotoxicity of Trichloroethane in a Model of Murine Splenic Injury

“…However, the Agency for Toxic Substances and Disease Registry (ATSDR) indicated that TCE affects many internal organs within the cardiovascular and the nervous systems [30]. Despite the TCE safe profile claimed in the aforementioned reports, TCE toxicity was documented by several studies in many animal models [31][32][33][34]. Moreover, prior studies have reported that perinatal exposure to TCE affects the development of the brain, liver, adipose tissue and adversely affects their functions in animals [1,[21][22][23][24][25].…”

Effect of methanolic fraction of Kalanchoe crenata on metabolic parameters in adriamycin-induced renal impairment in rats

“…The apparent cause of death in mice at the higher doses may be due to respiratory depression or/and to methanol (solvent) poisoning, since earlier studies with aqueous ethanol extract of K. crenata did not show any overt sign or death in acute toxicity. [816] These results suggest that MEKC possesses low toxicity since the LD50 is higher than 2 g/kg and inferior to 5 g/kg and represents 65 and 88 times, respectively, the assay doses. [17]…”

Tracking health threat from gaseous organic mixture in industry

“…Typical VOCs species have been con rmed to be deleterious such as benzene, formaldehyde, trichloroethane, etc. (21)(22)(23)(24), whilst new conclusion is continuously deepening understanding of the pathogenicity of different species, for example, chloroform, ethylbenzene, naphthalene, etc. (7,25,26) Based on toxicology, exposure experiments and eld monitoring were widely conducted to assess the health risk of speci c population groups (27)(28)(29)(30)(31).…”