Comparison between 3‐MCPD and its palmitic esters in a 90‐day toxicological study

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). BMD 10 and BMDL 10 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 (BMD 10 ) 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 BMDL 10 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, BMD 10 for severe renal and testicular damage were 41.1 and 64.4 mg/kg b.w. per day, respectively. The corresponding BMDL 10 were 17.4 and 44.3 mg/kg b.w. per day. CFP/EFSA/CONTAM/2009/01. Accepted for publication on 22 August 2011.The present document has been produced and adopted by the bodies identified above as author (s). In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the author (s) in the context of a grant agreement between the European Food Safety Authority and the author (s). The present document is published complying with the transparency principle to which the European Food Safety Authority is subject. It may not be considered as an output adopted by EFSA. EFSA reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors. 90-day toxicological study of 3-MCPD and its dipalmitateThe present document has been produced and adopted by the bodies identified above as author (s). In accordance with Article 36 of Regulation (EC) No 178/2002, this task has been carried out exclusively by the author (s) in the context of a grant agreement between the European Food Safety Authority and the author (s). The present document is published complying with the transparency ...

Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate-induced toxicity in rat kidney

“…Whereas the toxicological properties of 3-MCPD have been extensively studied in the past decades, only few studies were conducted to examine the toxicological properties of 3-MCPD fatty acid esters so far. Histopathological examination has confirmed that kidney is also the critical organ for 3-MCPD ester, but the observed changes after treatment with 3-MCPD dipalmitate in a 90-day oral rat study were slighter in comparison with equimolar 3-MCPD treatment (Barocelli et al 2011). A more recent oral 13-week study with rats revealed similar subchronic toxic effects of 3-MCPD fatty acid esters in comparison with free 3-MCPD (Onami et al 2014b).…”

“…per day 3-MCPD dipalmitate or 7.37 mg/kg b.w. per day 3-MCPD) (Barocelli et al 2011). In another study, Wistar rats were treated with 12.3 mg/kg b.w.…”

“…So far, the molecular mechanisms leading to renal toxicity are not fully understood. Based on in vivo experiments, it was shown that 3-MCPD is predominantly conjugated to glutathione and subsequently converted to 3-MCPD mercapturate which is then excreted with the urine (Barocelli et al 2011). Moreover, it was shown that 3-MCPD can be oxidized via β-chlorolactaldehyde to β-chlorolactic acid, finally yielding oxalic acid (Bakhiya et al 2011;Lynch et al 1998).…”

Analysis of occurrence of 3-monochloropropane-1, 2-diol (3-MCPD) in food in Europe in the years 2009-2011 and preliminary exposure assessment

“…Toxicological data on 3-MCPD esters are scarce. A sub-chronic toxicity study in rats administered equimolar doses of free 3-MCPD or a di-ester (di-palmitate) via gavage confirmed that the kidneys and testes are the main target organs for 3-MCPD toxicity as well as for the 3-MCPD di-ester studied, although the effects were milder and proportional to the urinary excretion of metabolites, which was lower than that observed for free 3-MCPD (Barocelli et al, 2011). Benchmark doses for renal and testicular damage were higher for the di-ester compared to those calculated for 3-MCPD, probably due to a slower and/or lower bioavailability and excretion rate (Barocelli et al, 2011).…”

Determination of 3-Monochloropropane-1,2-Diol Esters in Edible Oil―Method Validation and Estimation of Measurement Uncertainty

“…Recently, a few studies (Barocelli et al 2011;Liu et al 2012;Tee et al 2011) had evaluated toxicological properties of 3-MCPD esters using in vitro and in vivo approaches and confirmed the oral toxicity and cytotoxicity of 3-MCPD mono-and di-fatty acid esters. Studies showed the occurrence of 3-MCPD-esters in fatty food stuffs (Doležal et al 2005;Hamlet and Sadd 2004;Zelinková et al 2009;Zelinková et al 2006), even in human breast milk (Zelinková et al 2008).…”