Toxicological evaluation of rapeseed products in a subacute feeding study in rats.

Groups of 15 male rats were fed ad libitum for 4 weeks standard diet containing 0, 2.5, 5 or 10% rapeseed protein isolate (RPI), 2.5, 5 or 10% rapeseed extraction residue (RER) or 10% casein. Body weight gain and food intake were recorded weekly. Clinical chemistry analyses, haematology, urinalysis, organ weights and histology were performed terminally. Serum alanine aminotransferase was decreased by RPI, RER and casein, while serum albumin only increased in rats fed RER. Microscopic examinations revealed abnormalities in liver and kidneys of animals at the 10% RPI, RER and casein levels. The absolute liver weights showed increases in the 5 and 10% RER groups and in the 10% RPI group. The relative kidney weights were reduced at all RER levels and in the 2.5% RPI group. Antithyroid activity of the rapeseed products were not noted.

[The prenatal toxicity of butenylisothiocyanate in rats]. / Untersuchungen der Pränataltoxizität von Butenylisothiocyanat an Ratten.

Butenyl isothiocyanate (BylITC), the hydrolysis product of the glucosinolate gluconapin, present in various cruciferous vegetables and in rapeseed, was administered in oral doses of 0, 50, 100 and 150 mg/kg to pregnant rats on day 12 to 19 of gestation. Maternal toxicity was indicated by reduced body weight gain and increases in the weights of liver and kidneys. BylITC doses of 100 and 150 mg/kg caused retardation of fetal growth and ossification.

Effects of 5-vinyloxazolidine-2-thione on lactating rats and their sucklings.

5-vinyloxazolidine-2-thione (VOT) administered orally to lactating rats was found to be efficiently transferred to the sucklings via the milk. In mothers the exposure to VOT resulted in an increased percentage of neutrophils, a decreased percentage of lymphocytes and increases in the relative weights of liver and thyroid. Suckling rats showed a decreased number of leucocytes, increases in the relative weights of liver and thyroid and structural changes in the thyroid. Male sucklings were more affected than female pups. The antithyroid effects were clearly related to the maternally administered VOT doses.

Subacute oral toxicity study of benzyl isothiocyanate in rats.

The subacute toxicity of benzyl isothiocyanate (BITC) was investigated in male rats given oral doses of 0, 50, 100 and 200 mg/kg body weight/day for 4 weeks. Body weight gain and food consumption were decreased with increasing doses of BITC. Haematological changes of toxicological relevance were observed in the highest dose group. BITC administration resulted in increased serum cholesterol level in all treatment groups and decreased serum triglycerides level at 200 mg/kg. Renal dysfunction was indicated by reduced urine volume, proteinuria and enhanced urinary lactate dehydrogenase activity. BITC exposure also affected the weights of various organs and caused histological changes in the ductus choledochus, liver, ileum and mesenteric lymph nodes.

[Toxicological effect of a fatty acid mixture in rats]. / Toxikologische Wirkungen eines Fettsäuregemisches bei Ratten.

The effects of a fatty acids mixture containing nearly 50% odd numbered fatty acids (PC-Säure) were studied in a subchronic toxicity test in male and female rats. The animals received PC-Säure in their diet at levels of 0, 1.25, 2.5 and 5% for 13 weeks. Food intake was increased at 5% PC-Säure level in males. Food efficiency was initially decreased in males and females of this group. Ingestion of PC-Säure resulted in increases of the urine volume and the urinary lactate dehydrogenase activity in both sexes. Male and female rats fed PC-Säure showed elevated serum activities of alkaline phosphatase and leucine aminopeptidase and decreases in serum cholesterol and triglycerides. Dietary PC-Säure elevated the serum creatinine content in males at the two highest levels. A transitory increase in the activity of the serum alanine aminotransferase was observed in females fed 5% PC-Säure. Increased liver and kidney weights were found in both sexes.

[Toxicological evaluation of saccharose carbonic acid esters in basic subchronic feeding trials with rats. 1. Effect of saccharose fatty acid polyester]. / Toxikologische Beurteilung von Saccharosecarbonsäureestern auf der Grundlage subchronischer Fütterungsversuche mit Ratten. 1. Mitt. Wirkung von Saccharosefettsäurepolyester.

Groups of male and female rats received a sucrose fatty acid polyesters containing product (SPE) in their diet for 13 weeks at levels of 0, 5, 10 or 15%. Additional groups were pair-fed to the high-dose SPE-group (standard diet, 92.5%) or given food containing 7.5% hydrogenated lard (HF) or 4.5% fatty acid ethyl ester (FEE). Compared to the controls, there were increases in the food intake in males and females of the SPE-groups, HF- group and FEE-group. Male rats fed SPE showed increases in serum urea nitrogen at all levels, in serum alkaline phosphatase activity and urinary glucose excretion at 10 and 15%, in serum leucine amino-peptidase at 15%. In females dietary SPE increased the blood glucose content and serum alkaline phosphatase activity at 15% and the serum leucine aminopeptidase activity at 10 and 15%.

[Toxicologic evaluation of sucrose carbonic acid esters in basic subchronic feeding studies in rats. 2. Effect of sucroacetoglycerides]. / Toxikologische Beurteilung von Saccharosecarbonsäureestern auf der Grundlage subchronischer Fütterungsversche mit Ratten. 2. Mitt. Wirkung von Sucroacetoglyceriden.

Groups of male and female rats received a sucroacetoglycerides containing product (SAG) for 3 months at dietary levels of 0, 2.5, 5 and 10%. Food consumption was initially increased in females at all SAG-levels. After two weeks significant increases in food intake were observed in males and females fed 10% SAG throughout the feeding period. The serum analysis revealed significantly elevated activity in serum alkaline phosphatase at the highest SAG-level in males and females after 6 weeks and in females after 13 weeks. Histological changes related to the SAG-feeding were noted in the intestinal lymph nodes of male and female animals fed 10% SAG. The no-adverse effect level established in this subchronic feeding study was 5% SAG in the diet of rats, equivalent to a daily intake of 3.6 g/kg body weight in males and 4.0 g/kg in females.

[Dietary fiber. Effect on colon carcinogenesis]. / Ballaststoffstudie Wirkungen auf Coloncarcinogenese.

The etiopathogenesis of colon carcinogenesis is supposed to be a two-step process consisting of initiation and promotion. In human nutrition the range of xenobiotics acting possibly as initiators occurs mostly in very low concentrations. Therefore, performing a one-factorial consideration they are not claimed seriously to account for initiation. On the contrary, it can be taken for granted that bile acids exert promoting effects in connection with colon carcinogenesis. All factors influencing the promoting effect of bile acids are able to do so probably due to a decrease of pH and as a result the shift of the two bile acid fractions in favour of the soluble fraction, and/or due to the intensification of shift of bile acid metabolism (7-alpha-dehydroxylase). These processes are indirectly influenced to a large extent by the lipid content of food as a result of cholegenesis induction. The "protective Effect" of dietary fibre in colon carcinogenesis (reduced number of tumour carriers, and/or number of tumors per animal) cannot been interpreted as such. Only a delayed promotion phase could been proven. It can be reached only by plant products (bran, lupin), but not by dietary fibre in general.

[Progress report. What can one expect from a "functional prenatal toxicology?"]. / Fortschrittsbericht. Was kann man von einer "funktionellen Präntaltoxikologie" erwarten?

In the strategy of investigation applied and demanded in prenatal toxicology partial aspects have been overstressed until now, although here as well as in postnatal toxicology the problems should be viewed in its complexity (in this case, F1-generation in its several pre- and postnatal stages of development). Therefore, there was the urgent need to summarize the existing methods of functional investigation in the field of prenatal toxicology and to compare them with conventional morphological methods as to their meaningfulness and sensitivity. As a result, the routine introduction of clinical-functional investigations is demanded.

[The subacute toxicity of glucosylthiazolidine-4-carbonic acid in rats]. / Untersuchung der subakuten Toxizität von Glucosylthiazolidin-4-carbonsäure an Ratten.

Glucosylthiazolidine-4-carbonic acid, an intermediate of the Maillard reaction between D-glucose and L-cysteine, was given in doses of 0, 25, 50 or 100 mg/kg b.w. by oral intubation to male and female rats for 21 days. General appearance, growth, food consumption, haematology, urine analysis and serum chemistry including determinations of enzyme activities, organ weights and macroscopic and microscopic pathology were used as criteria for adverse effects. Effects on the kidneys were indicated by oliguria and decreased specific gravity of the urine in males and histopathological changes of the proximal tubules in females. The no-effect dose established from this study is 25 mg/kg b.w.

[The use of image analysis in nutritional toxicology--determination of goitrogenic effects]. / Anwendung der Bildanalyse in der Ernährungstoxikologie--Bestimmung goitrogener Effekte.

The estimation of the colloid area in PAS-stained thyroid slices were used for the proof of goitrogenic dose-effect-relations in nutritional toxicology.

[Progress report. Factors influencing nutritional toxic effects]. / Fortschrittsbericht. Einflussfaktoren auf ernährungstoxikologische Effekte.

The basis of the requirement for nutrio-toxicological model investigations is the result of many years of international experience. They are, however, limited for pragmatic reasons to standardized one-dimensional test conditions and can only be partially compared with the variable exposure conditions of man. Therefore, we have tried to review the practical significance of factors influencing nutrio-toxic effects. It has been shown that due to physiological and genetic differences, different lifestyle, biogeochemical and nutritional factors, additional occupational exposure as well as spontaneous diseases individual sensitivity shows a great variation range in man and laboratory animals. The multiple exposure which is common practice makes it difficult to provide proven evidence. The safety factor used for the extrapolation of results obtained in animal experiments as compared with man is a suitable pragmatic safety measure, but in the case of 1:100 as to the order of magnitude it is not always in accordance with the range of response to xenobiotics in a human population. This fact raises the necessity of searching for so-called "risk-groups" in the population. Additionally, the possible acceleration of spontaneous diseases by exposure to xenobiotics has to be taken into consideration.

[The subchronic toxicity of 5-vinyloxazolidine-2-thione in rats]. / Untersuchung der subchronischen Toxizität von 5-Vinyloxazolidin-2-thion an Ratten.

Groups of male and female rats received 5-vinyloxazolidine-2-thione (VOT) in their drinking water for 13 weeks at concentrations of 0, 10, 25, 50 or 100 mg/l and 0, 2.5 or 5 mg/l respectively. Compared with the controls, there were decreases in food intake and growth of females given VOT-doses of 10 mg/l and higher. Liquid intake was reduced in males and females of the highest dose group. Terminal haematological examination revealed an increase in white cell count at the 50 and 100 mg levels in females and a reduction in the red cell count at 100 mg/l in males. Organ weight changes were dose-related increases in the relative thyroid and liver weight and a decrease in the relative thymus weight. Structural and functional changes of the thyroid were observed in animals at levels of 10 mg/l and higher. Histological examinations of the kidneys showed tubulonephrosis in animals at and above a VOT-level of 5 mg/l. The no-observed-effect level (NOEL) established from these studies was 2.5 ml VOT/l drinking water (approximately equivalent to an daily intake of 0.4 mg/kg body weight).

Short-term toxicity study of allyl isothiocyanate in rats.

Allyl isothiocyanate (AITC) was given in doses of 0, 10, 20, or 40 mg/kg (5 days/week) by oral intubation to male rats for up to 6 weeks. The highest dosage level caused a decrease in body weight, thymus weight, blood glucose and serum globulin levels. Haematological examination revealed an increased percentage of neutrophils and a decreased percentage of lymphocytes after treatment for 2 weeks. Increased liver and adrenal weights were found in all test groups. Renal dysfunction was indicated by increased urinary aspartate amino-transferase activity, reduced urine volume and changes in the specific gravity of the urine. Histopathological changes were observed in the kidneys of animals at dosages of 20 and 40 mg/kg and in the livers of animals at the highest dosage level.

Is the variational scope of individual sensitivity given enough consideration in evaluation of risks caused by toxicological substances in food?

The contemporary concept of evaluation of risks with humans caused by xenobiotics in food is critically reviewed. In this context it is pointed out that epidemiologic studies, in most cases, give little reliable evidence only. Mankind's risk factors are of a multi-dimensional composition, depending on genetic aspects and the differring health and nutrition statuses of the individuals. This leads to an enormously wide scope of variations in the individual sensitivity to xenobiotics. Contemporary knowledge leaves the question open, whether predisposed population groups are always sufficiently protected by the level of the permissible amount of xenobiotics.