Toxicological responses in F344 rats following repeated dose sub-acute and sub-chronic dietary exposures to the food processing-induced contaminant 2-monochloro-1,3-propanediol (2-MCPD)

Abstract

In addressing a regulatory toxicological data gap to identify the hazard of the process-induced food contaminant 2-monochloro-1,3-diol (2-MCPD), two independent live bioassays were conducted according to the OECD TG-407 and -408. Weanling F344 rats (n = 10–12 rats/group/sex) were fed AIN-93G diets containing 2-MCPD to provide estimated daily doses of (a) 0 (control), 25 or 50 mg/kg BW for 28 days, and (b) 0 (control), 0.5, 2, 10 or 40 mg/kg BW for 90 days. Toxicological apical endpoints including histopathology were evaluated. In both studies, compared to the respective controls, the most critical 2-MCPD response was observed in the hearts; with secondary effects in the spleen and kidneys. Relative heart weights were increased in both sexes, together with non-neoplastic lesions in females (at 50 mg/kg BW), and in both males and females (at 40 mg/kg BW g). For the hearts, no-observed adverse effect levels (NOAELs) of 2-MCPD exposure were determined as 50 and 10 mg/kg BW for males, and 25 and 10 mg/kg BW for females, in the 28- and 90-day studies, respectively. These two regulatory-compliant rodent bioassays provide hazard identification data that strongly determined cardiotoxicity as the primary adverse outcome of 2-MCPD when exposed through the diet.