A new human pathology with visceral accumulation of long-chain n-alkanes; tissue distribution of the stored compounds and pathophysiological hypotheses

Salvayre, Robert; Nègre, Anne; Rocchiccioli, F.; Duboucher, Christophe; Maret, Arlette; Vieu, Claude; Lageron, A; Polonovski, J.; Douste‐Blazy, Louis

doi:10.1016/0005-2760(88)90234-2

Cited by 24 publications

(26 citation statements)

References 23 publications

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“…In contrast to the F-344 rat response, human lipogranulomas have been described as benign, circumscribed lesions that contain mineral oil droplets in the center, but without evidence of inflammation, fibrosis, or clinically significant liver dysfunction (45). Furthermore, accumulation in humans is not unique to mineral oil and also has been described for plant long-chain alkanes (such as those that occur in leaves or fruit peel cuticles and in nut and seed oils and waxes) and those that are produced by animals (such as butter fat, fish oils, beeswax, and lanolin) (3,11,17,31,42 (7, 8, 15-17, 20, 38-41). Likewise, these publications indicate that metabolism of hydrocarbons shows species differences and that metabolism is probably mediated by cytochrome P-450 in the liver and in the intestine of some species (7,15,20,24,29).…”

Section: Hydrocarbon Analysesmentioning

confidence: 97%

Ninety-Day Feeding Study in Fischer-344 Rats of Highly Refined Petroleum-Derived Food-Grade White Oils and Waxes

et al. 1996

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Subchronic 90-day feeding studies were conducted in male and female (F-344) rats on highly refined white mineral oils and waxes representative of those used for food applications. The goal was to help clarify the mixed results found in other toxicity studies with laboratory animals. Seven white oils and 5 waxes were fed at dietary doses of 20,000, 2,000, 200, and 20 ppm and compared with control groups on untreated diet; toxicity was assessed at 90 days and also after a reversal period of 28 days and/or 85 days. Higher molecular-sized hydrocarbons (microcrystalline waxes and the higher viscosity oils) were without biological effects. Paraffin waxes and low-to midviscosity oils produced biological effects that were inversely related to molecular weight, viscosity, and melting point; oil type and processing did not appear to be determinants. Biological effects were more pronounced in females than in males. Effects occurred mainly in the liver and mesenteric lymph nodes and included increased organ weights, microscopic inflammatory changes, and evidence for the presence of saturated mineral hydrocarbons in affected tissues. Inflammation of the cardiac mitral valve was also observed at high doses in rats treated with paraffin waxes. Further studies are required to elucidate the mechanism for the responses observed and the relevance of these inflammatory responses in the F-344 rat to other species, including humans.

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Section: Hydrocarbon Analysesmentioning

confidence: 97%

Ninety-Day Feeding Study in Fischer-344 Rats of Highly Refined Petroleum-Derived Food-Grade White Oils and Waxes

et al. 1996

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“…In three spleens exhibiting severe follicular lipidosis, the MOSH concentration ranged from 3.4 to 4.2 mg/g tissue, whereas in three spleens considered negative histologically, the alkane concentration was below 0.3 mg/g. Lipid analysis of tissues from an adult male after sudden death (affected with diffuse visceral granuloma containing lipophilic crystallised material) showed the presence of long-chain n-alkanes with 29, 31 and 33 carbon atoms suspected to be of plant origin (Salvayre et al, 1988). A study of the n-alkane distribution in patient tissues showed a major accumulation in lumbo-aortic lymph nodes, adrenal glands, lung (the highest levels were found in lung granulomas) and liver; significantly lower amounts were detected in myocardium and kidney, whereas no detectable level was found in brain.…”

Section: Data From Humansmentioning

confidence: 99%

“…The authors noted that beside the pharmacological treatment, other sources of exposure, including the dietary and occupational exposure, may have contributed to the presence of MOH in the liver of the patient. Salvayre et al (1988) reported a case of a 55 year old man who died because of ventricular fibrillation. The authors reported that the man used to eat approximately one kilogram of unpeeled apples every day, which would correspond to an intake of about 10 mg of natural long chain n-alkanes per day.…”

Section: Cases Of Intoxication Associated With Intake Of Moshmentioning

confidence: 99%

Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

107

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Consumers are exposed to a range of mineral oil hydrocarbons (MOH) via food. Mineral oil saturated hydrocarbons (MOSH) consist of linear and branched alkanes, and alkyl-substituted cyclo-alkanes, whilst mineral oil aromatic hydrocarbons (MOAH) include mainly alkyl-substituted polyaromatic hydrocarbons. Products, commonly specified according to their physico-chemical properties, may differ in chemical composition depending on the oil source. Technical grade MOH contain 15 -35 % MOAH, which is minimised in food grade MOSH (white oils). Major sources of MOH in food are food packaging and additives, processing aids, and lubricants. Estimated MOSH exposure ranged from 0.03 to 0.3 mg/kg b.w. per day, with higher exposure in children. Specific production practices of bread and grains may provide additional MOSH exposure. Except for white oils, exposure to MOAH is about 20 % of that of MOSH. Absorption of alkanes with carbon number above C 35 is negligible. Branched and cyclic alkanes are less efficiently oxidised than n-alkanes. MOSH from C 16 to C 35 may accumulate and cause microgranulomas in several tissues including lymph nodes, spleen and liver. Hepatic microgranulomas associated with inflammation in Fischer 344 rats were considered the critical effect. The no-observed-adverse-effect level for induction of liver microgranulomas by the most potent MOSH, 19 mg/kg b.w. per day, was used as a Reference Point for calculating margins of exposure (MOEs) for background MOSH exposure. MOEs ranged from 59 to 680. Hence, background exposure to MOSH via food in 1 On request from the European Commission, Question No EFSA-Q-2010-00170, adopted on 3 May 2012. 2 SUMMARYFollowing a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on mineral oil hydrocarbons (MOH) in Food. Mineral oil hydrocarbons occur in food both as a result of contamination and from various intentional uses in food production. In order to assess the need for possible regulatory measures as regards MOH in food, EFSA was requested to assess the risks related to their occurrence in food. More specifically, the opinion should evaluate whether new toxicity data are available and whether the current acceptable daily intakes (ADIs) are still applicable, explore whether certain classes (or subclasses) of MOH are more relevant due to their toxicity or to differences in the way they are metabolised by the human body, and identify the different background sources, other than from adulteration or misuse, of MOH occurrence in food. In addition a dietary exposure assessment was requested for the general population and for specific subgroups of the population (e.g. infants, children and people following specific diets), by taking into account the background occurrence of MOH in food. Included in the request was also to advise on MOH and food classes to be included if monitoring were to be set up for their presence in food.The scientific literature and other sources were s...

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“…In two case reports in human patients with sudden death, the presence of abnormal compounds, notably, giant macrophagic lung granulomas of "needle-like" inclusions at microscopic examination in one case were described (Salvayre et al, 1988) and pulmonary granulomatosis and storage of "crystallized fatty substance" in the lymph nodes, spleen, adrenal glands and the lungs in the other case (Duboucher et al, 1989). Both patients were reported to eat daily about 1 kg of unpeeled apples.…”

Section: Hydrocarbons (N-alkanes N-alkenes)mentioning

confidence: 99%

Scientific Opinion on the re-evaluation of candelilla wax (E 902) as a food additive

2012

EFSA Journal

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The Panel on Food Additives and Nutrient Sources added to Food (ANS) delivers a scientific opinion re-evaluating the safety of candelilla wax (E 902). Candelilla wax (E 902) is authorised in the EU as a food additive as a glazing agent. It has been evaluated by the Scientific Committee on Food (SCF) and by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The JECFA and the SCF did not establish an Acceptable Daily Intake (ADI) but considered the use of candelilla wax as a glazing agent acceptable. Candelilla wax is obtained from leaves of candelilla plants Euphorbia antisyphilitica found in semi-desert regions. It is a complex mixture composed of wax hydrocarbons, wax, resin esters, lactones, free wax resin alcohols, and free wax resin acids. The Panel considered that absorption of candelilla wax is expected to be low, and that upon absorption the components would be incorporated into normal metabolic pathways. The Panel noted that there were limited data comparing the composition of the candelilla wax tested with the specification of the food additive. However the Panel considered that the materials tested were likely to be broadly similar in composition to the food additive. Overall, the Panel considered that the available data suggest that candelilla wax is not genotoxic. The Panel considered that long-term toxicity data on candelilla wax were lacking and therefore did not establish an ADI. However, the Panel noted that available toxicity studies consistently reported no findings associated with intake of the main components constituting candelilla wax. Furthermore, consideration of the exposure estimates to candelilla wax, using the Maximum Permitted Level (MPL) of carnauba wax, indicated sufficient margins of safety. This allowed the Panel to conclude that the use of candelilla wax as a food additive with the currently authorised uses would not be of safety concern

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A new human pathology with visceral accumulation of long-chain n-alkanes; tissue distribution of the stored compounds and pathophysiological hypotheses

Cited by 24 publications

References 23 publications

Ninety-Day Feeding Study in Fischer-344 Rats of Highly Refined Petroleum-Derived Food-Grade White Oils and Waxes

Ninety-Day Feeding Study in Fischer-344 Rats of Highly Refined Petroleum-Derived Food-Grade White Oils and Waxes

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Scientific Opinion on the re-evaluation of candelilla wax (E 902) as a food additive

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