Two‐year toxicity and carcinogenicity study of acrolein in rats

Abstract

Five-hundred and sixty Sprague-Dawley rats were randomized into one control and three treatment groups (70 of each sex per group). Animals were treated by daily gavage with 0.0, 0.05, 0.5 and 2.5 mg kg-1 acrolein in water (10 ml kg-1). These dosing levels were selected as a result of a 6-week range-finding study. Ten rats of each sex per group were sacrificed at 1 year, and the remainder of the animals were treated for 102 weeks. Daily observations wer made, and various clinical, hematological and urine parameters were measured after 3, 6, 12 and 18 months of treatment and immediately prior to termination. All animals, whether found dead or sacrificed, were subject to necropsy and both absolute and relative organ weights were recorded. An extensive array of tissues were examined microscopically for all test animals. The only effects noted for treated rats that were statistically different from controls were consistent depression of creatinine phosphokinase levels, which was difficult to explain, and consistent increases in early cumulative mortalities in both males and females. There was no significantly increased incidence of microscopic lesions in treated rats, whether neoplastic or non-neoplastic. This study clearly demonstrates the lack of neoplastic response in Sprague-Dawley rats as a result of being treated with acrolein by gavage.

Introduction and Toxicology of Fungicides

“…The only effects noted were decreased serum creatinine kinase and increased early cumulative mortality. There were no significant increases in neoplastic or non-neoplastic histopathology (Parent et al, 1992a).…”

Toxicology and risk assessment of acrolein in food

“…No increased incidence of microscopically detectable lesions was reported. However, increased mortality rates were observed, which were dose-dependent [39].…”

CONTRIBUTION OF CYP3A5 TO HEPATIC AND RENAL IFOSFAMIDEN-DECHLOROETHYLATION

“…In parallel, ifosfamide is also metabolized by N-dechloroethylation to 2-dechloroethylifosfamide (2-DCEI), 3-dechloroethylifosfamide (3-DCEI), and an equivalent molar amount of chloroacetaldehyde. Both acrolein and chloroacetaldehyde cause toxicity in LLC-PK1 cells (Mohrmann et al, 1992(Mohrmann et al, , 1993; however, acrolein does not impair the function of isolated perfused rat kidneys or after long-term exposure in animal models (Parent et al, 1992;Zamlauski-Tucker et al, 1994). Chloroacetaldehyde has consistently shown a concentration-dependent cytotoxic effect in several in vitro models (i.e., porcine or rabbit cultured renal tubules and isolated perfused rat kidneys) with a minimum toxic concentration that ranges from 12.5 to 64 M (Mohrmann et al, 1993;Springate, 1997;Springate et al, 1999).…”