Subchronic Toxicity of a Fluoroalkylethanol Mixture in Rats

Abstract

The objective of this study was to evaluate the subchronic toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluoroorganic compounds that are used as protectants and surfactants. The test substance was administered daily by gavage to Sprague–Dawley rats as a suspension in aqueous methylcellulose. The dosages were 0, 25, 100, or 250 mg kg^{− 1} day^{− 1}. A 1- and 3-month recovery period was included to evaluate the reversibility of toxic effects. No test substance–related mortality or neurotoxicity occurred. Body weights and/or nutritional parameters were significantly reduced at 100 and 250 mg kg^{− 1} day^{− 1}, and these effects were reversible. Broken and absent teeth were observed in rats dosed with 250 mg kg^{− 1} day^{− 1}, and microscopic tooth lesions (ameloblast degeneration/disorganization) occurred at 100 and 250 mg kg^{− 1} day^{− 1} and persisted with decreased severity throughout recovery. Decreased red cell mass parameters occurred at 90 days in the 250 mg kg^{− 1} day^{− 1} group, but red cell counts were normal thereafter during recovery. A persistent elevation of liver weights was seen in groups given ≥ 100 mg kg^{− 1} day^{− 1}. The increased weights correlated with microscopic hepatocellular hypertrophy only in males and females administered 250 mg kg^{− 1} day^{− 1}. Hepatic β-oxidation was increased in a dose-dependent manner and persisted through 1 month of recovery at 250 mg kg^{− 1} day^{− 1}. Increased kidney weights were observed at 25 (females only), 100, and 250 mg kg^{− 1} day^{− 1}. These elevated weights persisted in the high dose after recovery and correlated with microscopic tubular hypertrophy (males only). Thyroid follicular hypertrophy was present at 100 and 250 mg kg^{− 1} day^{− 1} but was not present after recovery. Total fluorine in whole blood increased with continuous dosing and achieved steady state in approximately 42 days. Both plasma and urine fluoride levels were elevated in adose-dependent manner. Under the conditions of the study, the no-observed adverse effect level for this mixture was 25 mg kg^{− 1} day^{− 1} for subchronic toxicity.

Key Words: :

• Fluoroalkylethanol mixture
• Rat
• Subchronic toxicity