Rat liver metabolism of benzo[b]naphtho[2,1-d]thiophene

Murphy, Sharon E.; Amin, Shantu; Coletta, Kristin A.; Hoffmann, Dietrich

doi:10.1021/tx00028a006

Cited by 26 publications

(22 citation statements)

References 13 publications

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“…The metabolism of thioarenes (sulphur-containing PAHs) such as dibenzothiophene, benzo(b)naphtho(2,1-d)thiophene or benzo(b)phenanthro(2,3-d)thiophene has been investigated after oral administration to rats (Ambaye et al, 1961) or using rodent liver subcellular fractions (Murphy et al, 1992;Yuan et al, 2003). The in vivo experiment conducted by Ambaye and co-workers on dibenzothiophene showed that this compound is eliminated through urine as 1-hydroxydibenzothiophene-5,5-dioxide, indicating that oxidation occurred on the sulphur atom and on the benzene ring.…”

Section: Sulphur Compoundsmentioning

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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Section: Sulphur Compoundsmentioning

confidence: 99%

Scientific Opinion on Mineral Oil Hydrocarbons in Food

2012

EFS2

107

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“…Thiophene is a sulfur‐containing heterocyclic hydrocarbon that has been detected in a number of environmental sources as various derivatives 1,2 . Christomanos and Scholz first described neurotoxicity in dogs that had been given thiophene subcutaneously 3 .…”

Section: Introductionmentioning

confidence: 99%

Thiophene, a sulfur‐containing heterocyclic hydrocarbon, causes widespread neuronal degeneration in rats

2000

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compounds. [4][5][6][7] In addition, liver necrosis has been described in animals given thiophene, 8 and liver dysfunction has been reported in some patients treated with thiophene derivatives. 9,10 These observations give rise to the idea that although primary neuronal damage occurs during thiophene intoxication, hepatic injury may influence the progression of brain lesions because acute or chronic liver disease can cause metabolic alterations in the brain. 11,12 The purpose of this investigation was to determine whether the hepatotoxicity of thiophene influences brain pathology, and to investigate the mechanisms involved in neuronal degeneration resulting from thiophene poisoning. The results of the present study demonstrate that the progression of brain lesions was not accelerated by thiophene-induced hepatic injury and that the regional distribution of brain lesions induced by thiophene is different from that caused by methyl mercury poisoning.

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“…The metabolites of benzo[ b ]naphtho[2,1- d ]thiophene ([2,1]BNT) and benzo[ b ]phenanthro[2,3- d ]thiophene include dihydrodiols with a bay-region double bond, as well as the sulfoxide and the sulfone [8,9]. In addition, [2,1]BNT-3,4-diol, which forms a bay-region diol epoxide, was as mutagenic in Salmonella TA100 as the parent compound [2,1]BNT; however, [2,1]BNT-1,2-diol was not mutagenic [10].…”

Section: Introductionmentioning

confidence: 99%

Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene

Swartz¹,

King²,

Nesnow³

et al. 2009

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, but only a few have been studied for health effects. We evaluated the mutagenicity in Salmonella TA98, TA100, and TA104 of two sulfur-containing derivatives of benzo[c]phenanthrene, phenanthro[3,4-b]thiophene (P[3,4-b]T), and phenanthro[4,3-b]thiophene (P[4,3-b]T) as well as their dihydrodiol and sulfone derivatives. In addition, we assessed levels of stable DNA adducts (by 32P-postlabeling) as well as abasic sites (by an aldehydic-site assay) produced by six of these compounds in TA100. P[3,4-b]T and its 6,7- and 8,9-diols, P[3,4-b]T sulfone, P[4,3-b]T, and its 8,9-diol were mutagenic in TA100. P[3,4-b]T sulfone, the most potent mutagen, was approximately twice as potent as benzo[a]pyrene in both TA98 and TA100. Benzo-ring dihydrodiols were much more potent than K-region dihydrodiols, which had little or no mutagenic activity in any strain. P[3,4-b]T sulfone produced abasic sites and not stable DNA adducts; the other five compounds examined, B[c]P, B[c]P 3,4-diol, P[3,4-b]T, P[3,4-b]T 8,9-diol, and P[4,3-b]T 8,9-diol, produced only stable DNA adducts. P[3,4-b]T sulfone was the only compound that produced significant levels of frameshift mutagenicity and induced mutations primarily at GC sites. In contrast, B[c]P, its 3,4-diol, and the 8,9 diols of the phenanthrothiophenes induced mutations primarily at AT sites. P[3,4-b]T was not mutagenic in TA104, whereas P[3,4-b]T sulfone was. The two isomeric forms (P[3,4-b]T and P[4,3-b]T) are apparently activated differently, with the latter, but not the former, involving a diol pathway. This study is the first illustrating the potential importance of abasic sites in the mutagenicity of thia-PAHs.

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Rat liver metabolism of benzo[b]naphtho[2,1-d]thiophene

Cited by 26 publications

References 13 publications

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Scientific Opinion on Mineral Oil Hydrocarbons in Food

Thiophene, a sulfur‐containing heterocyclic hydrocarbon, causes widespread neuronal degeneration in rats

Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene

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