Metabolism of nephrotoxic<i>cis‐</i>and<i>trans</i>‐decalin in fischer‐344 rats

Olson, Carl; Yu, Kefu; Serve, M. P.

doi:10.1080/15287398609530868

Cited by 21 publications

(14 citation statements)

References 8 publications

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“…The metabolic pathways of cis-and trans-decalin in rats was reported by Olson et al (1986) and by Dill et al (2003a). Both isomers were found to be metabolised differently in males and females.…”

Section: Moshmentioning

confidence: 98%

“…Extracts of kidney samples from male rats treated with cis-and trans-decalin yielded cis-2-decalone and trans-2-decalone, respectively. There was no trace of decalin metabolites in female kidney extracts (Olson et al 1986). Dill et al (2003a) showed that the retention of decalin and decalone in male rat kidney was linked with the accumulation of α 2u -globulin in this organ occurring subsequently to the production of this protein in the liver.…”

Section: Moshmentioning

confidence: 99%

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Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

102

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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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Section: Moshmentioning

confidence: 98%

Section: Moshmentioning

confidence: 99%

Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

102

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“…Olson recently studied the metabolism of 3 and 4 in male and female Fischer 344 rats (7). The results of this study are summarized in Table 1.…”

Section: Omentioning

confidence: 76%

A Study of the Toxicity of the Metabolites of the Cruise Missile Fuel JP-10 on Several Animal Species.

Serve¹

1986

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“…They possibly indicate that hydroxylation of the original substances takes place prior to binding with alpha2~t-globulin (Olson et al 1985(Olson et al , 1986Henningsen et al 1987Charbonneau et al 1987a, b;Lock et al 1987;Parnell et al 1988). Such a hydroxylation step may therefore represent a prerequisite before binding to alpha2~t-globulin can occur.…”

Section: R O M An Inspection Of the Calculated Partition Coefficientsmentioning

confidence: 89%

“…Paraffin sections of the kidneys were stained with hematoxilin and eosin, as well as with azan according to Heidenhain. The following scale was used for semiquantitative grading of the occurrence of hyaline droplets in light microscope examination of azan-stained slides: 0 = no droplets 1 = occasional droplets in some proximal tubules 2 = mild response in a large number of proximal tubules 3 = moderate response with an increase in droplets in cells and more widespread cortical distribution 4 = extensive response with a marked increase and widespread distribution a Relative activity level from Craig (1986); comparative activity level of the reference compound PS-6 gasoline (positive control) is given as 3+ b Wright Patterson Air Force Base study, no detailed experimental conditions given c Cis/trans isomer ratio not specified; according to Kanerva et al (1987 a, b, c), Stone et al (1987), Olson et al (1986) both isomers induce hyaline droplet accumulation and light hydrocarbon nephropathy…”

Section: Methodsmentioning

confidence: 99%

Relationships between structure and induction of hyaline droplet accumulation in the renal cortex of male rats by aliphatic and alicyclic hydrocarbons

et al. 1990

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A rapidly growing list of hydrocarbons has been reported to induce morphological changes in the kidney of adult male rats, beginning with hyaline droplet accumulation (HDA) followed by the development of granular casts, later on chronic nephrosis as sequela, and finally renal adenomas and carcinomas. The present study focuses on identifying structure-based properties common to HDA-inducing aliphatics and cycloaliphatics. On the basis of rank-ordered activities reported in the literature, a calculated n-octanol-water partition coefficient above 3.5 and the presence of an isopentyl structural moiety appear to be associated with HDA-inducing activity in aliphatics. A binding site model for highly active aliphatics has been derived by superimposing their minimum energy conformations along the common isopentyl substructure and calculating the union volume of their respective van der Waal (VDW) volumes. Generalization of this model to include cycloaliphatics has been achieved by maximizing the steric overlap of the VDW volumes of the compounds with their binding site union volume. HDA-inducing cycloaliphatics are correctly identified on the basis of their negligible excess volume. This approach has been used to predict the HDA-inducing activity of previously untested compounds. Eighteen aliphatic/cycloaliphatic hydrocarbons were screened in a study on adult male Wistar rats treated with 250 mg/kg per day for 5 days. Azan-stained kidney sections were semiquantitatively evaluated for the presence of HDA. The predicted and observed HDA activities were in very good agreement.

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Metabolism of nephrotoxiccis‐andtrans‐decalin in fischer‐344 rats

Cited by 21 publications

References 8 publications

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Scientific Opinion on Mineral Oil Hydrocarbons in Food

A Study of the Toxicity of the Metabolites of the Cruise Missile Fuel JP-10 on Several Animal Species.

Relationships between structure and induction of hyaline droplet accumulation in the renal cortex of male rats by aliphatic and alicyclic hydrocarbons

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