A 24-month dietary carcinogenicity study of DAG in mice

Chengelis, Christopher P.; Kirkpatrick, Jeannie B.; Bruner, Richard H.; Freshwater, Les; Morita, Osamu; Tamaki, Yasushi; Suzuki, Hiroyuki

doi:10.1016/j.fct.2005.06.007

Cited by 17 publications

(6 citation statements)

References 28 publications

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“…Male and female Crl:CD‐1 (ICR) BR mice (50 animals/group) were fed a diet containing diacylglycerol (rich in unsaturated fatty acids (> 95%)) for 24 months (Chengelis et al., ). Dietary concentrations (% diacylglycerol/% triacylglycerol) were 0%/6.0% (control), 1.5%/4.5%, 3.0%/3.0% and 6.0%/0%.…”

Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of mono‐ and di‐glycerides of fatty acids (E 471) as food additives

Younes¹,

Aggett²,

Aguilar³

et al. 2017

EFS2

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The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re-evaluating the safety of mono-and di-glycerides of fatty acids (E 471) when used as a food additive. The Panel considered that it is very likely that hydrolysis of mono-and di-glycerides of fatty acids by lipases in the gastrointestinal tract would occur, resulting in the release of glycerol and fatty acids. Glycerol (E 422) and fatty acids (E 570) have been re-evaluated and the Panel concluded that there was no safety concern regarding their use as food additives. Toxicological studies with mono-and di-glycerides rich in unsaturated fatty acids were considered for the re-evaluation of E 471. No evidence for adverse effects was reported in short-term, subchronic studies, chronic, reproductive and developmental toxicity studies. Neither carcinogenic potential nor a promotion effect in initiation/promotion was reported. The available studies did not raise any concern with regard to genotoxicity. The refined estimates were based on 31 out of 84 food categories in which E 471 is authorised. The Panel noted that the contribution of E 471 represented at the mean only 0.8-3.5% of the recommended daily fat intake. Based on the approach described in the conceptual framework for the risk assessment of certain food additives re-evaluated under Commission Regulation (EU) No 257/2010 and taking into account the considerations mentioned above, the Panel concluded that there was no need for a numerical acceptable daily intake (ADI) and that the food additive mono-and di-glycerides of fatty acids (E 471) was of no safety concern at the reported uses and use levels. The Panel recommended some modifications of the EU specifications for E 471.

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Section: Assessmentmentioning

confidence: 99%

Re‐evaluation of mono‐ and di‐glycerides of fatty acids (E 471) as food additives

Younes¹,

Aggett²,

Aguilar³

et al. 2017

EFS2

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“…a resultant false-positive rate of approximately 10%. The use of this multiple comparison adjustment procedure is widely used in the interpretation of rodent cancer bioassays (Chengelis et al, 2006;Heim et al, 2007;Long et al, 2009;Shuey et al, 2007;Thomas et al, 2007). Application of Lin and Rahman's criteria for statistical significance for trend to the astrocytoma data in the current study suggests that the observed marginal dose effect is probably a false positive.…”

Section: Discussionmentioning

confidence: 75%

“…The Haseman procedure has been extended to trend tests by Lin and Rahman (), who recommended significance levels of P < 0.005 and P < 0.025 for testing positive linear trend in incidence rate for common and rare tumors, respectively, with a resultant false‐positive rate of approximately 10%. The use of this multiple comparison adjustment procedure is widely used in the interpretation of rodent cancer bioassays (Chengelis et al ., ; Heim et al ., ; Long et al ., ; Shuey et al ., ; Thomas et al ., ). Application of Lin and Rahman's criteria for statistical significance for trend to the astrocytoma data in the current study suggests that the observed marginal dose effect is probably a false positive.…”

Section: Discussionmentioning

confidence: 99%

Two‐year drinking water carcinogenicity study of methyl tertiary‐butyl ether (MTBE) in Wistar rats

Dodd

Willson

Parkinson

et al. 2011

J of Applied Toxicology

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Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE.

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“…DAG at dietary concentrations up to 9.5% for one year had no effect on normal dog growth and development, in comparison to TAG [ 38 ]. In mice, DAG at dietary concentrations up to 6.0% for 24 months produced no signs of systemic toxicity and had no effect on the incidence of neoplastic findings [ 39 ]. Most of studies investigating a chronic dietary toxicity of DAG reported that DAG did not produce systemic toxicity and had no effect on the incidence of neoplastic findings.…”

Section: A Safety Of a Chronic Consumption Of Dagmentioning

confidence: 99%

Diacylglycerol oil for the metabolic syndrome

Yanai

Tomono

Ito

et al. 2007

Nutr J

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Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered.

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A 24-month dietary carcinogenicity study of DAG in mice

Cited by 17 publications

References 28 publications

Re‐evaluation of mono‐ and di‐glycerides of fatty acids (E 471) as food additives

Re‐evaluation of mono‐ and di‐glycerides of fatty acids (E 471) as food additives

Two‐year drinking water carcinogenicity study of methyl tertiary‐butyl ether (MTBE) in Wistar rats

Diacylglycerol oil for the metabolic syndrome

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