Subchronic oral toxicity study of furan in B6C3F1 Mice.

Furan is a heterocyclic organic compound formed during heat treatment for processing and preservation of various types of food. Rodent studies have previously shown that furan is a hepatocarcinogen. Those studies were conducted over a high dose range, which induced tumors at nearly 100% incidence at all doses. This ninety-day gavage study in mice was conducted to extend the dose to a lower range (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg body weight [bw] per day) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects, including those affecting clinical biochemistry, hematology, tissue morphology, and histopathology. The liver was the primary target organ with dose-dependent toxicity. Liver weights were increased at the 8.0 mg/kg bw dose in females only. Levels of the serum enzyme alanine transaminase, representative of liver damage, were increased three-fold at the highest dose. Histological changes in the liver were observed at 2.0 and 8.0 mg/kg bw in both sexes. Although clinical parameters were also altered for the kidney, these differences were not accompanied by histological changes. Based on these clinical biochemical and histological changes, a no-observed adverse effect level of 0.12 mg/kg bw per day of furan in mice is suggested.

Subchronic oral toxicity study of furan in Fischer-344 rats.

Rodent studies have shown that furan is a hepatocarcinogen. Previous studies conducted with high doses showed tumors at nearly 100% incidence at all doses. In this paper, a ninety-day gavage experiment conducted with lower doses (0.0, 0.03, 0.12, 0.5, 2.0, and 8.0 mg/kg bw) to identify a no-observed adverse effect level for hepatotoxicity and to characterize non-neoplastic effects including gross changes and histopathology, clinical biochemistry, hematology, and immunotoxicology is reported. As indicated by changes in serum biomarkers, increased liver weights and gross and histological lesions, the liver is the major target organ affected by furan. There were no changes in body weights, food consumption, or histology in other organs. Some of the serum electrolyte markers, including phosphorus, were altered. There was a significant increase in serum thyroxine and triidothyronine in males. This increase was not accompanied by histological thyroid changes. Immunophenotypic analysis showed that thymic lymphocyte maturation was altered in male rats. Although altered clinical biochemistry and hematological parameters were observed at a dose of > 0.5 mg/kg bw, mild histological lesions in the liver were observed at > 0.12 mg/kg bw. Based on this finding, a furan dose of 0.03 mg/kg bw was proposed as the no-observed adverse effect level for hepatic toxicity.

Development of an analytical method and survey of foods for furan, 2-methylfuran and 3-methylfuran with estimated exposure.

Furan has been found to form in foods during thermal processing. These findings, a classification of furan as a possibly carcinogenic to humans, and a limited amount of data on the concentration of furan in products on the Canadian market prompted the authors to conduct a survey of canned and jarred food products. Methyl analogues of furan, 2-methylfuran and 3-methylfuran, were analysed concurrently with furan via a newly developed isotope dilution method, as these analogues were detected in foods in the authors' earlier work and are likely to undergo a similar metabolic fate as furan itself. The paper reports data on 176 samples, including 17 samples of baby food. The vast majority of samples were packaged in cans or jars. Furan was detected above 1 ng g(-1) in all non-baby food samples with a median of 28 ng g(-1) and concentrations ranging from 1.1 to 1230 ng g(-1). Also, 96% of these samples were found to contain 2-methylfuran above 1 ng g(-1) with a median of 12.8 ng g(-1) and a maximum concentration of 152 ng g(-1), while 81% of samples were found to contain 3-methylfuran above 1 ng g(-1) with a median of 6 ng g(-1) and a maximum concentration of 151 ng g(-1). Similarly, furan was detected above 1 ng g(-1) in all baby food samples with a median of 66.2 ng g(-1) and concentrations ranging from 8.5 to 331 ng g(-1). Also, 100% of these samples were found to contain 2-methylfuran above 1 ng g(-1) with a median of 8.7 ng g(-1) and a maximum concentration of 50.2 ng g(-1), while 65% of samples were found to contain 3-methylfuran above 1 ng g(-1) with a median of 1.6 ng g(-1) and a maximum concentration of 22.9 ng g(-1). Additionally, three coffee samples were analysed 'as is', without brewing, and were found to have high levels of furans, especially 2-methylfuran, at a maximum of 8680 ng g(-1). Using this data set, dietary exposures to furan and total furans were calculated. Average furan and total furan intakes by adults (> or = 20 years) were estimated at approximately 0.37 and 0.71 microg kg(-1) of body weight day(-1) respectively.

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.

Permeability of the blood-brain barrier to mannitol in the rat following 2450 MHz microwave irradiation.

The radiotracer method of Oldendorf was used to determine if 2450 MHz continuous wave (CW) microwave energy increases blood-brain barrier permeability to [14C]mannitol, which is normally excluded from entering the brain. Anesthetized, adult rats were irradiated singly for 30 min in the quiet zone of an anechoic chamber, at average power densities from 0.1 to 30 mW/sq.cm. Afterwards each rat received an intracarotid bolus injection of [14C]mannitol/[3H]water mixture and was decapitated 15 sec later. Uptake of [14C]mannitol relative to the highly permeable reference substance, [3H]water, was calculated as the brain uptake index (BUI) for 4 brain regions. Mean BUI values for tissues from the microwave-irradiated rats did not differ significantly from sham-irradiated animals, and a microwave influence on barrier permeability was not evident. Irrespective of treatment, BUI values for cerebellum and medulla were much higher and more variable than values for cortex or diencephalon, and were associated with reduced absorbance or retention of [3H]water. Because of a compromising influence of the vertebral arterial supply on the distribution of intracarotid-injected radiotracers, BUI measurements in caudal brain regions are probably unreliable unless accompanied by data on regional radioisotope concentrations. The absence of such data in an earlier BUI study, suggests that increases in BUI for cerebellum and medulla attributed to microwaves were possibly misinterpreted as differences in barrier permeability to [14C]saccharides, when in fact changes in blood flow and [3H]water influx or egress were responsible.