Comparison between 3-MCPD and its palmitic esters in a 90-day toxicological study
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Abstract
A 90-day toxicological study was carried out administering equimolar doses of either 3-MCPD (respectively 29.5, 7.37, and 1.84 mg/kg b.w. per day) or 3-MCPD dipalmitate (respectively 156.75, 39.19, and 9.78 mg/kg b.w. per day) to both male and female rats (10 animals per group). Urinary 3-MCPD and 3-MCPD mercapturate were used to monitor exposure to both 3-MCPD and its dipalmitate, and to assess the bioavailability of the latter (equimolar doses of dipalmitate gave rise to urinary metabolites lower by 30 % as compared to the administration of 3-MCPD). Histopathological examination confirmed that the kidney and, in male rats, the testes are critical organs for 3-MCPD. Changes observed after treatment with dipalmitate were similar, but milder and proportional to the urinary excretion of metabolites. The overall picture of nephrotoxicity was consistent with tubulotoxicity, which in female rats was severe enough to cause acute renal failure in 20 to 50 % of animals receiving high doses of 3-MCPD (29.5 mg/kg b.w. per day). BMD10 and BMDL10 for mortality in female rats were 7.4 and 2.3 mg/kg b.w. per day, respectively. At such high doses, male rats showed extensive testicular toxicity, with extensive cell depletion. Nephrotoxicity was milder and apparently chronic in nature. Benchmark doses (BMD10) for severe damage to renal and testicular structures in male rats were 5.6 and 8.4 mg/kg b.w. per day, respectively. The corresponding BMDL10 were 2.5 and 6.0 mg/kg b.w. per day. Different BMDs were obtained for 3-MCPD dipalmitate, depending on the contribution of the 3-MCPD moiety to the molecule and probably a slower and/or lower bioavailability and excretion rate. In male rats, BMD10 for severe renal and testicular damage were 41.1 and 64.4 mg/kg b.w. per day, respectively. The corresponding BMDL10 were 17.4 and 44.3 mg/kg b.w. per day.