Precautionary allergen labelling: perspectives from key stakeholder groups.

Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counterproductive for consumers with food allergies. This review aims to summarize the perspectives of all the key stakeholders (including clinicians, patients, food industry and regulators), with the aim of defining common health protection and risk minimization goals.

Dietary caffeine reduces the genotoxicity of MeIQx in the host-mediated assay in mice.

The influence of dietary caffeine on the genotoxicity of the cooked food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) was evaluated using the host-mediated assay in mice. For four weeks, BALB/c mice were fed a purified diet with or without caffeine (0.01% wt/wt in the diet).

Tumorigenicity of a combination of psoriasis therapies.

Coal tar, a tumour initiator, and dithranol, a tumour promoter, are used in the treatment of psoriasis. Topical treatment of mice with pharmaceutical formulations of these two agents, at therapeutic doses, induced skin papillomas in a classical two-stage carcinogenesis protocol, while treatment with either agent alone did not. This finding has implications for the use of both agents in combination in the treatment of psoriasis.

Influence of dietary fat on DNA binding by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the mouse liver.

Female BALB/c mice were fed either a low (1%)-fat or one of three high-fat diets (containing an additional 25% (w/w) beef fat, hydrogenated vegetable oil or non-hydrogenated vegetable oil) for 4 wk. They were then orally treated with 10 mg 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)/kg body weight and killed 6 hr later. Consumption of the hydrogenated vegetable oil was accompanied by increased DNA adduct formation in mice.

Effect in vitro of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on the hepatic activation of dietary genotoxins by rat post-mitochondrial fractions.

The effect of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on the conversion of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to its genotoxic metabolites was investigated using a modified bacterial mutation assay. The assay used Salmonella typhimurium TA98 as an indicator of the mutagenicity and hepatic post-mitochondrial fractions (S-9) from male Sprague-Dawley rats as the activating system. All three fatty acids inhibited the mutagenicity of IQ without effect on the uptake of the active metabolites and/or on the DNA repair processes within the bacterial cell.

Inhibition of the metabolism of mutagens occurring in food by arachidonic acid.

Hepatic microsomal fractions (microsomes) were prepared from male Sprague-Dawley rats. The effect of arachidonic acid on the conversion of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to its genotoxic metabolites was investigated using a modified bacterial mutation assay (indicator: Salmonella typhimurium TA98). Arachidonic acid inhibited the mutagenicity of IQ without effect on the uptake of the active metabolites and/or on the DNA-repair processes within the bacterial cell.

Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens.

Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay.

Roles of dietary fat and fibre in the disposition and metabolism of carcinogens associated with foods.

The abilities of dietary fibre (wheat bran) or fat (olive oil) to modify the genotoxicity of radiolabelled MeIQ were evaluated in mice using in vivo and in vitro bacterial mutation assays. Bran reduced genotoxicity by restricting uptake of MeIQ from the gut lumen. In contrast, feeding mice a high fat diet led to increased hepatic conversion of MeIQ to an active genotoxin.

Modification of in vivo heterocyclic amine genotoxicity by dietary flavonoids.

Female BALB/c mice were fed diets containing equimolar amounts of quercetin or its glycoside, rutin, for 5 weeks. These mice were used either in host-mediated bacterial mutation assays or as sources of hepatic microsomes. In host-mediated bacterial mutation assays using radiolabelled mutagens, the heterocyclic amines 2-amino-3,5-dimethyl[4,5-f]imidazoquinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) induced greater numbers of revertants in mice fed either of the flavonoid diets compared with control.

Covalent binding of [2-14C]2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) to mouse DNA in vivo.

Female BALB/c mice were administered intragastrically with equimolar amounts of either [2-14C]2-amino-3,8-dimethyl-[4,5-f]quinoxaline (MeIQx) or 2-acetylamino[9-14C]fluorene (2AAF). DNA was isolated from tissues of mice killed either 6 or 24 h after administration. Analysis of lvier DNA nucleotide digests by HPLC analysis revealed that all of the radioactivity was attributable to adduct formation.

Effect of dietary fibre on the mutagenicity and distribution of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ).

Female BALB/c mice were fed either a fibre-free diet or one supplemented with 30% wheat-bran for 5 weeks. The ability of these mice to convert MeIQ to a bacterial mutagen in vivo was determined using intrasanguinous host-mediated bacterial mutation assays. Less mutagenic activity was detected in the livers of mice fed the bran-supplemented diet compared with those fed the fibre-free diet.

Distribution of radiolabelled [2-14C]IQ and MeIQx in the mouse.

The kinetics of distribution of radiolabelled [2-14C]IQ (2-amino-3-methylimidazo[4,5-f]quinoline) and [2-14C]MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) following the oral administration to BALB/c mice of single doses were studied. Both compounds were taken up into the blood-stream and other tissues rapidly after administration and approximately 20-25% of the radioactive dose of IQ or MeIQx was excreted in urine over 6 h, reflecting the rapid absorption of the mutagens. Significantly greater levels of MeIQx than IQ were isolated from the lungs and blood of treated mice.

Caffeine inhibits hepatic-microsomal activation of some dietary genotoxins.

Hepatic microsomal fractions (microsomes) were prepared from female BALB/c mice. The potential of caffeine to modify the ability of microsomes to convert the heterocyclic aromatic amines MeIQ, Trp-P-2 and MeIQx, to bacterial mutagens (indicator: Salmonella typhimurium TA98) was investigated. Caffeine inhibited mutagenicity and did so by inhibiting microsomal metabolism of the three compounds, rather than by altering uptake of the active mutagens and/or interacting with the DNA repair processes in the bacterial cell.

Counteraction of the genotoxicity of some cooked-food mutagens by biogenic amines.

The biogenic amines tryptamine, 5-hydroxytryptamine, tyramine and histamine were assessed for their abilities to modify the genotoxicity of the cooked-food mutagens IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2. These measurements were made using a bacterial mutation assay with hepatic fractions from either SWR mice or DSN Syrian hamsters as the activating system and Salmonella typhimurium TA98 as the indicator organism. Although histamine had very little effect on the genotoxicity of these mutagens, the other amines reduced genotoxicity, with tryptamine and 5-hydroxytryptamine exerting the greatest effect.

High levels of dietary fat: alteration of hepatic promutagen activation in the rat.

Male Ola:Sprague-Dawley rats were fed diets containing either low or high levels of fats. After being fed these diets for 4 weeks, the rats were killed and individual hepatic postmitochondrial (S9) fractions were prepared. The ability of these fractions to convert the heterocyclic aromatic amines (HAAs)--2-amino-3-methylimidazo[4,5-f]quinoline; 2-amino-3,4-dimethylimidazo[4,5-f] quinoline; and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (compounds produced during the cooking of proteinaceous food)--to bacterial mutagens was studied, with the use of Salmonella typhimurium TA98 as indicator.

The hepatic conversion of some heterocyclic amines to bacterial mutagens is modified by dietary fat and cholesterol.

Groups of Sprague-Dawley rats were fed on diets containing increasing amounts of beef dripping, but having a constant cholesterol content. One group of rats was fed on a diet containing no dripping and no added cholesterol (control). We have studied the ability of individual hepatic S9 preparations to activate the cooked food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX) to bacterial mutagens using Salmonella typhimurium TA98 as indicator.

Use of continuous culture to study the gastric microflora of a hypochlorhydric patient.

A method of maintaining the microflora obtained from the hypochlorhydric stomach of a patient suffering from hypogammaglobulinaemia has been developed using continuous culture (chemostat) techniques. The culture was maintained at pH 8.0 (the pH of the original gastric juice) and subsequently at pH 7.

Effects of plant-derived flavonoids and polyphenolic acids on the activity of mutagens from cooked food.

The ability of 3 plant flavonoids (morin, myricetin and quercetin) and 4 polyphenolic acids (caffeic acid, chlorogenic acid, ellagic acid and ferulic acid) to inhibit the genotoxic effects of a number of cooked-food mutagens (IQ, MeIQ, MeIQx, Trp-P-1 and Trp-P-2), was investigated in a bacterial mutation assay using Salmonella typhimurium TA98 as indicator and hepatic S9 mixes from either SWR mice or Syrian hamsters as metabolic activating systems. Although the polyphenolic acids failed to have an effect, the flavonoids generally inhibited IQ, MeIQ, MeIQx and Trp-P-1 induced mutagenesis in a dose-dependent manner, irrespective of the source of S9. This was not the case with Trp-P-2 where the flavonoids were only observed to inhibit when SWR mouse S9 but not Syrian hamster S9 was used.

Metabolic conversion of IQ and MeIQ to bacterial mutagens.

The metabolic conversion of 2-amino-3-methyl- and 2-amino-3,4-dimethyl-imidazo[4,5-f]quinoline (IQ and MeIQ respectively) to bacterial mutagens was studied using a bacterial mutation assay. Studies were performed using S9 fractions derived from either corn oil (uninduced) or Aroclor-1254-treated Sprague-Dawley rats. Aroclor 1254 treatment lowered the S9 protein concentration required for optimum levels of mutagenesis, enhanced the numbers of mutants observed and altered the effects of metabolic inhibitors and cofactors added to the assay.

Pilot study of the effect of diet on the mutagenicity of human faeces.

A healthy non-smoking man, consuming a normal 'western' diet (meat, vegetables, bread and alcohol) collected five consecutive complete bowel movements. He then added an extra 150 g of fat (from butter, cheese, milk, chocolate, peanuts, bacon and eggs) to his daily diet for 2 weeks, and collected four further consecutive bowel movements in the second week. After 6 months on his normal diet, he added 30 g of wheat bran to his daily diet for 3 weeks, and collected four complete stool samples in the third week.

Activation of the food mutagens IQ and MeIQ by hepatic S9 fractions derived from various species.

The ability of hepatic S9 mixes derived from different rodent species (rat, mouse, Syrian and Chinese hamster) to activate the mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was investigated using Salmonella typhimurium strain TA98. In general, the mutagenicity of IQ and MeIQ was greatest in the presence of S9 fractions from Swiss albino mice and least from fractions derived from Chinese hamsters. However, treatment of rats or hamsters with Aroclor 1254 had little or no effect on the activation of IQ or MeIQ to mutagens.

The role of DNA-repair processes in N-nitrosopyrrolidine-induced mutagenesis.

The cytotoxic and mutagenic effects of increasing concentrations of N-nitrosopyrrolidine (NPYR) were studied using various DNA repair mutants of Escherichia coli together with rat-liver S9 activation system. Irrespective of which strain was used, the cytotoxic effects of NPYR were similar to those observed in the parent strain. Mutagenicity studies revealed that the uvrA- derivative was more mutable than its repair proficient parent.