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Biomedical subjects

J Gry

Publications and source records attributed to J Gry.

11 recordsLinked to original sources

Subchronic oral toxicity study on the three flavouring substances: octan-3-ol, 2-methylcrotonic acid and oct-3-yl 2-methylcrotonate in Wistar rats.

Groups of 10 male and 10 female rats were administered 0, 25, 100 or 400 mg octan-3-ol/kg body weight per day, 77 mg 2-methylcrotonic acid/kg body weight per day or 163 mg oct-3-yl 2-methylcrotonate/kg body weight per day by gavage for 90 days. Relative liver weights of high-dose octan-3-ol males, and males and females dosed with oct-3-yl 2-methylcrotonate were significantly greater than those of the control. In male and female rats dosed with the highest level of octan-3-ol and in male rats dosed with 2-methylcrotonic acid, incidences of bile duct proliferation were increased. In the kidneys of males dosed with mid- and high level of octan-3-ol and oct-3-yl 2-methylcrotonate, tubular karyomegaly and desquamation of tubular epithelial cells were observed. Based on increased liver weight and microscopic evaluation of the liver and kidney, a no-observed-effect level (NOEL) of 25 mg/kg for octan-3-ol in rats was established. The histopathological evaluation of the liver of rats dosed with oct-3-yl 2-methylcrotonate revealed lesions corresponding to the lesions seen in rats dosed mid-dose with octan-3-ol. This observation is in accordance with the general assumption that oct-3-yl 2-methylcrotonate is completely hydrolysed to octan-3-ol and 2-methylcrotonic acid. However, when comparing the liver histopathology of oct-3-yl 2-methylcrotonate and 2-methylcrotonic acid and the kidney lesions of all three substances, conflicting results were seen and the present study does not allow the conclusion to be drawn that oct-3-yl 2-methylcrotonate and structurally-related esters are completely hydrolysed, at least under the conditions of the present study.

Administration, Oral↗

Influence of storage and household processing on the agaritine content of the cultivated Agaricus mushroom.

Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethyl-phenylhydrazine) was identified and quantified by high-pressure liquid chromatography and used as a marker for the occurrence of phenylhydrazine derivatives in the cultivated Agaricus bitorquis and A. garicus hortensis mushrooms. Although relatively high levels of agaritine (around 700 mg kg(-1)) could be found in freshly harvested A. bitorquis from early flushes, samples from supermarkets contained less agaritine. The content of 28 samples varied between 165 and 457 mg kg(-1), on average being 272 +/- 69 mg kg(-1). The highest amounts of agaritine were found in the skin of the cap and in the gills, the lowest being in the stem. There was no significant difference in agaritine content of the two mushroom species in our study. Pronounced reduction in agaritine content was observed during storage of mushrooms in the refrigerator or freezer, as well as during drying of the mushrooms. The degree of reduction was dependent on the length and condition of storage and was usually in the region 20-75%. No reduction in agaritine content was observed during freeze-drying. Depending on the cooking procedure, household processing of cultivated Agaricus mushrooms reduced the agaritine content to various degrees. Boiling extracted around 50% of the agaritine content into the cooking broth within 5min and degraded 20-25% of the original agaritine content of the mushrooms. Prolonged boiling, as when preparing a sauce, reduced the content in the solid mushroom further (around 10% left after 2h). Dry baking of the cultivated mushroom, a process similar to pizza baking, reduced the agaritine content by approximately 25%, whereas frying in oil or butter or deep frying resulted in a more marked reduction (35-70%). Microwave processing of the cultivated mushrooms reduced the agaritine content to one-third of the original level. Thus, the exposure to agaritine was substantially less when consuming processed Agaricus mushrooms as compared with consuming the raw mushrooms. However, it is not yet known to what extent agaritine and other phenylhydrazine derivatives occurring in the cultivated mushroom are degraded into other biologically active compounds during the cooking procedure.

Agaricus↗

Stability of agaritine - a natural toxicant of Agaricus mushrooms.

Agaritine (N-(gamma-L(+)-glutamyl)-4-hydroxymethylphenylhydrazine) is a phenylhydrazine derivative found in the cultivated Agaricus mushroom which is claimed to give rise to carcinogenic products when metabolized. The stability of a synthetic sample of agaritine was tested in water and methanol. In tap water kept in open vials, agaritine was totally degraded within 48h. Since agaritine degradation was less pronounced in closed than in open vials, and slower in Milli Q water and, in particular, in Milli Q water purged with N(2), the degradation seems to be oxygen-dependent. The antioxidant dithiothreitol reduced the degradation. Four or possibly five ultraviolet-absorbing compounds were formed during degradation, but these have not yet been identified. Whereas the rate of degradation was similar at temperatures between 4 and 22 degrees C, it was quicker at an acidic than at a neutral pH. The latter observation was confirmed in experiments where agaritine was incubated in simulated gastric fluid (pH 1.2). The importance of the degradation when performing toxicological studies with agaritine is discussed.

Agaricus↗

Agaritine content in processed foods containing the cultivated mushroom (Agaricus bisporus) on the Nordic and the Czech market.

The level of agaritine was measured in fresh and canned cultivated mushroom (Agaricus bisporus) as well as in other food products containing A. bisporus, by reversed phase high performance liquid chromatography. The two fresh samples were purchased on the open market and contained 212 and 229 mg/kg, respectively. Of the 35 different trademarks of canned mushroom products studied, 25 were based on cut mushrooms and 10 on whole mushrooms. On average, whole mushrooms contained 14.9 +/- 6.7 mg agaritine per kg product whereas cut mushrooms contained 18.1 +/- 7.8 mg/kg. There was no statistically significant difference between these two values. Agaritine levels in brine were generally slightly lower than the levels detected in canned mushrooms. Thus, the level of agaritine in A. bisporus is reduced more than 10 times during the wet canning process, resulting in low levels in canned products. On a portion basis, somewhat higher amounts of agaritine may be found in some other food products (mushroom soup and pasta sauce) containing A. bisporus.

Agaricus↗

Failure of the cultivated mushroom (Agaricus bisporus) to induce tumors in the A/J mouse lung tumor model.

We studied whether the cultivated mushroom (Agaricus bisporus) or 4-(carboxy)phenylhydrazine (CP) induce lung adenomas in the A/J mouse lung tumor model. For 26 weeks female mice were fed a semisynthetic diet where 11 or 22% of the diet was replaced by freeze-dried mushrooms. The intake of the mushroom diets was equivalent to an intake of agaritine, the major phenylhydrazine derivative occurring in the mushroom, of 92 or 166 mg/kg body weight per day. The intake of CP was 106 mg/kg body weight per day. Neither the freeze-dried mushroom nor CP induced statistically significant increased numbers of lung adenomas in female A/J mice in the administered dosages.

Adenoma↗

Carcinogenicity study of the emulsifier TOSOM and the release agent TOS in Wistar rats.

Groups of 60 Wistar rats of each sex were fed diets containing 3, 6 or 12% of the margarine emulsifier TOSOM (thermally oxidized soybean oil interacted with mono- and diglycerides of fatty acids) for 2.5 yr. In addition, three groups of 60 rats of each sex were fed two products of the release agent TOS (thermally oxidized soybean oil) in dietary levels of 1.2% TOS(G) (TOS from Grindsted Product A/S, Denmark) and 0.3 and 1.2% TOS(N) (TOS from Nexus Aps, Denmark), respectively for 2.5 yr. 120 rats of each sex fed a diet containing mono- and diglycerides served as controls. The diets given to all groups were isocaloric. Clinical appearance, food consumption, body weight and weight gain, survival, haematology, and clinical chemistry parameters were examined. Gross and histopathological examinations, including neoplastic and non-neoplastic lesions, were performed on all groups. Time to occurrence of tumours was recorded. No substance-related effect, including carcinogenicity, was found.

Animals↗

HPLC profiles of mutagens in lean ground pork fried at different temperatures.

Ground lean pork was formed into patties and fried under ordinary conditions making sure that the crust was not charred. No fat was added when frying. The meat was fried at pan temperatures of 200 degrees C, 250 degrees C, and 300 degrees C until the temperature at the centre of the patties was either 65 degrees C or 70 degrees C. The crust was extracted with aqueous acid followed by concentration of the mutagens on an XAD-2 column and elution with acetone. The total mutagenic activity and high-pressure liquid chromatography (HPLC) analysis of the mutagenic components ("mutagrams") in the eluates were determined for the different frying procedures using the Salmonella/mammalian microsome test strain TA 98. Each 50 degrees C increase in the pan temperature (from 200 degrees C to 250 degrees C and from 250 degrees C to 300 degrees C) resulted in a doubling of the total mutagenic activity. The HPLC profiles of the mutagens were quite similar for the different frying temperatures, although a strong increase in the relative amount of more apolar mutagens was seen at 300 degrees C (the highest temperature). The major mutagenic activity of the HPLC fractions was confined to seven regions (mutagenic peaks) and a comparison of the HPLC profiles of the mutagens in fried beef and pork patties showed identical profiles. It is therefore concluded that the mutagenic compounds formed in fried beef and pork are similar in structure.

Animals↗

Animal feeding study with nitrite-treated meat.

In order to detect possible formation of carcinogenic N-nitroso compounds from nitrite and nitrosatable compounds in meat, studies were carried out with 70 male and 140 female F0 rats, divided into six groups, and 60, 100, 70, 60, 60 and 66 of their male and female offspring. One control group received casein and other groups chopped pork as the sole protein source (45%, mass/mass) on a fresh basis, either salted (sodium chloride) or not. For test groups, nitrite was also added to the meat before autoclaving and storing the diet and represented mass fractions of 200, 1 000 and 4 000 mg/kg, as sodium nitrite. The results do not demonstrate any effect on reproduction and no significant carcinogenic effect was revealed. However, an observed tendency toward an increased number of tumour-bearing rats in the highest dose group, plus the possible formation of carcinogenic N-nitroso compounds in nitrite-treated meat products, led to a recommendation to reduce the use of nitrite. Results from a concomitant study demonstrate that it is possible to produce many cured-meat products with the addition of only 50 mg/kg nitrite.

Animal Feed↗

Effects of rapeseed oil compared to hydrogenated marine oil in rats. Histopathological effects of erucic acid and isomers on the heart.

In a recent review on the role of fats in human nutrition Vergroesen and Gottenbos (1975) emphasize, that the presence of erucic acid isomers in hydrogenated marine oils (HMO) may constitute a toxicological problem as serious as erucic acid in rapeseed oil (RSO). On the contrary Christophersen et al. (1976) stress, that these fatty acids in HMO represent a minor toxicological problem, and that conclusions drawn from HMO to RSO are questionable. Preliminary studies at our institute indicate lipidosis in the heart both in rats fed RSO and HMO, containing equivalent amounts of erucic acid and erucic acid isomers respectively. Further experiments of longer duration are performed with HMO and RSO in order to compare the effect on the heart, especially in relation to the formation of cell necrosis.

Animals↗

Metabolism of L(+)-and D(-)-tartaric acids in different animal species.

L(+)-Tartaric acid, which is the naturally occurring form, is used as a food additive in a variety of foodstuffs. Recently, there has been an increasing interest in using synthetic (D,L)-tartaric acid as a substitute. Several toxicological studies have been published on L(+)-tartaric acid, but practically nothing concerning the racemic form. The metabolism of L(+)-tartaric acid has been investigated in a variety of species including man. Species differences have been noted in the ability to excrete the acid in the urine after oral administration. The decomposition of tartaric acid by the intestinal flora has been implicated as an important factor. (Underhill et al., 1931 a,b). In the present study the metabolic fate of L(+)- and D(-)-tartaric acids is compared in different species, in vivo after oral administration and in vitro after incubation with caecal extract.

Animals↗