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.
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.
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 dosedependent 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.
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