Highest Dietary Concentration Research Articles

Extended one-generation reproductive toxicity study evaluating gardenia blue in Sprague Dawley rats

Gardenia blue powder was administered at 0.5%, 2.5%, or 5.0% in feed to male and female Sprague Dawley rats in an Extended One-Generation Reproductive Toxicity Study (OECD Test Guideline 443). The dosed diet began 14 days before mating and was continued at the same concentration level for the entire study for all parental animals (P0) and offspring (F1). At weaning, offspring were allocated into one of 5 cohorts for different endpoints. P0 and F1 animals had blue urine, blue or black feces, and blue discolorations in gastrointestinal organs, mesenteric lymph nodes, and kidneys. This treatment-related finding was not considered adverse as there were no histopathologic correlates. There was a dose-related increase in sperm concentration in P0 and F1 males. There were dose-related increases in heart weights of F1 postnatal day (PND) 21 males, male and female thyroid weights, and female TSH levels of PND 91 F1 offspring, with no histopathological correlate. There were no consistent treatment-related adverse effects on any other parameters evaluated for general toxicity, reproductive toxicity, developmental neurotoxicity, or developmental immunotoxicity. The highest dietary concentration (5.0%) of gardenia blue powder was the no observed adverse effect level (NOAEL) for male and female rats at all life stages evaluated.

Extended One-Generation Reproductive Toxicity (EOGRT) study of benzoic acid in Sprague Dawley rats

Benzoic acid (BA) was administered in the diet to male and female Sprague Dawley Crl:CD(SD) rats in an OECD Test Guideline 443 Extended One-Generation Reproductive Toxicity (EOGRT) study to test for effects that may occur as a result of pre- and postnatal exposure. The study included cohorts of F1 offspring to evaluate potential effects of benzoic acid on reproduction, the developing immune system, and the developing neurological system with the inclusion of learning and memory assessments. Benzoic acid was incorporated in the diet at concentrations of 0, 7,500, 11,500, and 15,000 mg/kg diet (ppm). These concentrations were selected based on the results of preliminary studies, and, based on average food consumption, were intended to supply BA doses of approximately 0, 500, 750, and 1000 mg/kg bw/day. To avoid exceeding these target dose levels, the dietary concentrations were adjusted (based on historical control body weight and food consumption data) to maintain the target mg/kg bw/day dose levels during those life periods when food intake per unit of body weight was increased to support milk production by females (gestation and lactation) and rapid pup growth (post-weaning).In the parental (F0) generation, survival, clinical observations, organ weights, pathology, hematology, serum chemistry, urinalysis, and bile acids were unaffected by BA administration. Reproductive parameters were also unaffected by BA administration.In the F1 generation, survival, growth and developmental landmarks, organ weights, pathology, immunotoxicity assessment, and neurotoxicity and neurobehavioral parameters such as auditory startle response, locomotor activity, learning and memory assessments were unaffected by BA administration, as were clinical pathology (hematology, serum chemistry, urinalysis, bile acids and thyroid hormones) and reproductive performance. Similarly, no adverse effects or systemic toxicity were observed in the F2 generation.Overall, the highest dietary concentration (15,000 ppm), providing a dosage of approximately 1000 mg/kg bw/day, was the NOAEL for benzoic acid in this EOGRT study.

The effect of Artemisia annua on broiler performance, on intestinal microbiota and on the course of a Clostridium perfringens infection applying a necrotic enteritis disease model

The aerial parts of the plant Artemisia annua contain essential oils having antimicrobial properties against Clostridium perfringens Type A, the causal agent for necrotic enteritis in broilers. In two experiments, the influence of increasing dietary concentrations of dried A. annua leaves (0, 5, 10 and 20 g/kg) and n-hexane extract from fresh A. annua leaves (0, 125, 250 and 500 mg/kg) on broiler performance was investigated. Dried plant material decreased feed intake and body weight in a dose-dependent manner, and 10 and 20 g/kg diet tended to improve the feed conversion ratio. The n-hexane extract also reduced feed intake, but broiler weight tended to decrease only at the highest dietary concentration. The feed conversion ratio tended to improve when birds received 250 and 500 mg/kg n-hexane extract. In a third experiment, a necrotic enteritis disease model was applied to investigate the effect of the dietary addition of dried A. annua leaves (10 g/kg on top) or n-hexane extract of A. annua (250 mg/kg) on the severity of the disease in broilers. The addition of n-hexane extract reduced the intestinal C. perfringens numbers and the severity of the disease-related small intestinal lesions. Over the infection period from day 17 to day 27, birds supplemented with the n-hexane extract gained more weight than both the challenged control birds and birds receiving dried plant material. The results indicate that n-hexane extracts derived from A. annua can modulate the course of necrotic enteritis and compensate to a certain extent for the disease-associated weight losses.

Tissue lipid peroxidative responses in Atlantic salmon (Salmo salar L.) parr fed high levels of dietary copper and cadmium

Atlantic salmon (Salmo salar L.) parr were fed for one month on fish meal based diets supplemented with Cd (0, 0.7, or 204 mg Cd kg−1 DW) or Cu (0, 34, or 691 mg Cu kg−1 DW) to assess the effects of non-essential (Cd) and essential (Cu) dietary metals on lipid peroxidation and the oxidative defence system. Cadmium accumulated significantly in the liver, intestine, and kidney of 204 mg Cd kg−1exposed fish compared to controls. Copper accumulated significantly in the intestine, kidney, and liver of fish exposed to 691 mg Cu kg−1, and in the intestine of 34 mg Cu kg−1 exposed fish. Tissue Cu accumulation significantly increased intestinal and hepatic lipid peroxidation (as seen from thiobarbituric acid reactive substances, TBARS, levels) and subsequently decreased intestinal α-tocopherol levels and increased intestinal and hepatic selenium dependent glutathione peroxidase (SeGSH-Px) activity. Dietary Cd significantly reduced SeGSH-Px activity in the intestine and liver of 204 mg Cd kg−1 exposed fish compared to controls. No significant increase in tissue TBARS or reduction of α-tocopherol levels was observed in the intestine of fish exposed to dietary Cd, with exception of the highest exposure group (204 mg Cd kg−1). Dietary Cu caused depletion of tissue Se and glutathione levels, however the reduced availability of GSH and Se did not seem to explain the differences in SeGSH-Px activity. Dietary Cu had a direct effect on lipid peroxidation at a relatively low concentration (34 mg Cu kg−1). Cadmium indirectly affected tissue lipid peroxidation by damaging the oxidative defence system at the highest dietary concentration (204 mg Cd kg−1).

Comparative organophosphate-induced effects observed in adult and neonatal sprague–dawley rats during the conduct of multigeneration toxicity studies

Five organophosphates: tribufos, oxydemeton-methyl, fenamiphos, coumaphos, and trichlorfon were evaluated for their potential to produce reproductive and neonatal toxicity following continuous dietary exposure during multigenerational reproduction toxicity studies in the Sprague–Dawley rat. Dietary concentrations were selected to demonstrate parental effects in the high dose and provide for a no-adverse effect level at the low dose. There were no clinical signs observed in the adults or neonates during either generation. Significant effects on body weight and food consumption, when observed, were typically observed only with the highest dietary concentration and were greater in the second generation. Reproductive effects, including decreased fertility and mating indices, were only observed with test compounds and at dietary concentrations demonstrating effects on body weight and/or food consumption. Similarly, pup body weight was also affected by those test compounds that produced significant maternal effects during lactation. Significant inhibition of parental cholinesterase activities (plasma, erythrocyte, and brain) was similarly observed in both generations with all test compounds, with at least the highest concentrations. In general, females demonstrated greater enzyme inhibition than the males. For example, mean PChe inhibition considering both generations and all test compounds was 74% for the females, whereas inhibition was 51% in the males. Effects on cholinesterase activities in the neonates (Lactation Day 4) were, for most test compounds, below 10% at the highest dietary concentration. However, by Lactation Day 21, inhibition of enzyme activity (considering all test compounds at the highest concentration and all enzymes) was approximately 30%. The increase in inhibition is attributed to the consumption of the treated feed during the latter stages of lactation. Considering the relative maternal (termination) and neonatal (Lactation Day 4) cholinesterase effects at the highest dietary concentration, it was observed that the effects in the neonate were, for all organophosphates tested, significantly less than those observed in the dam.

Regulation of Adipsin and Body Composition in the Monosodium Glutamate (MSG)-Treated Mouse

Changes in food intake, serum adipsin, and obesity were evaluated in the MSG-treated mouse. In Experiment 1, mice treated with MSG had 50% lower serum adipsin and over 2-fold higher percentage of body fat than the lean controls. Both feeding caffeine and restricting intake normalized serum adipsin and caused weight loss, but did not normalize the percentage of body fat. No additional effect was gained by feeding isoproterenol or ephedrine in combination with caffeine. In Experiment 2, we separated the direct effect of caffeine from the associated depression in intake using a paired feeding design, and also determined the effects of selected adrenergic agents and somatotropin (S). Somatotropin increased weight gain and reduced the percentage of body fat in healthy and obese mice, and tended to lower serum adipsin. Caffeine clearly depressed intake, caused weight loss, and increased serum adipsin, but similar results were achieved by restricting intake. None of the adrenergic drugs tested changed serum adipsin. Ephedrine depressed food intake and caused weight loss, but reduced the percentage of body fat only at the highest dietary concentration (2000 mg per kg of diet). Phenylephrine reduced weight gain without a concomitant effect on the percentage of body fat, and isoproterenol did not influence weight gain or body fat.

Influence of faba bean tannins on male broiler chicks: evaluation of hulls from white- and coloured-flowered cultivars and of near-isogenic lines

SUMMARYThe hulls (seed coat) of tannin-free, white-flowered and tannin-containing, coloured-flowered faba beans (ViciafabaL.) were used in three experiments (1989–90) to investigate the effect of tannins on the apparent metabolizable energy corrected to zero nitrogen retention (AMEN) and apparent metabolizable nitrogen (AMN) of broiler chick diets.In Experiment 1, the effects of four rates of hull inclusion from one white- and one colouredflowered cultivar (0, 28, 56 and 84 g/kg) on dietary AMENand AMN were studied. There was a significant response of AMENto hull inclusion rate (P <0·001) but no inclusion rate × cultivar interaction. For dietary AMN there was a significant effect of hull inclusion rate (P <0· 001) but no inclusion rate x cultivar interaction.Experiment 2 consisted of two parts. In both, the total concentration of hulls was 227 g/kg but the ratio of white- to coloured-flowered hulls was varied in five increments; initially over the range 0·42–16·58 g/kg dry matter (DM) and subsequently, with another cultivar, 0·44–7·85 g/kg DM. Synthetic lysine and methionine were added to ensure that the basal diet was not limiting in these amino acids. A significant effect of tannin intake on dietary AMENand AMN was detected across the greater range of tannin concentrations (P <0·001) but not across the smaller one.Experiment 3 evaluated three pairs of near-isogenic faba bean lines differing only in the gene governing tannin content and flower colour. Diets were formulated using three bean inclusion rates; 200, 400 and 600 g/kg. At each rate the white- and coloured-flowered lines were mixed in the ratios 100:0, 75:25, 50:50, 25:75 and 0:100. The response in carcass nitrogen retention (CNR) to tannin intake was assessed at each bean inclusion rate and for each pair of lines.There was a significant effect of tannin intake on CNR in only one of the nine comparisons and in that case CNRincreasedas dietary content increased.It was concluded that faba bean tannins can have a negative effect on the dietary AMENand AMN for chicks when present at a sufficiently high dietary concentration. However, the highest dietary concentration of faba bean tannins in Expt 3 was 10·52 g/kg DM, giving a maximum daily intake of 1·03 g tannins for the two-bird experimental unit. At concentrations and intakes up to this there was no evidence to suggest that faba bean tannins had a significant adverse effect.

Effects of boron on growth and physiology in mallard ducklings

High concentrations of boron (B) have been associated with irrigation drainwater and aquatic plants consumed by waterfowl. Day-old mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) or diets containing 100, 400 or 1,600 ppm B as boric acid. Survival, growth and food consumption were measured for 10 weeks. At termination, blood and tissue samples were collected for biochemical assays and histological examination. The highest dietary concentration of B caused 10% mortality, decreased overall growth and the rate of growth (sexes combined), whereas lower concentrations of B altered growth only in females. Food consumption was lower during the first 3 weeks in the 1,600-ppm group and during the second week in all B-treated groups compared to controls. Hematocrit and hemoglobin were lower and plasma calcium concentration higher in the 1,600-ppm group compared to controls. Plasma triglyceride concentration was elevated in all B-treated groups. Brain B concentration increased to 25 times that of controls in the 1,600-ppm group. Brain ATP decreased with increasing dietary B. Brain acetylcholinesterase activity and total ATPase activity (in males) were elevated and protein concentration lowered in the 1,600-ppm group. Boron accumulated less in the liver than in the brain but resulted in an initial elevation of hepatic glutathione. These findings, in combination with altered duckling behavior, suggest that concentrations of B occurring in aquatic plants could adversely affect normal duckling development.

Toxicity of o‐cresol to mink and european ferrets

AbstractThe toxicity of o‐cresol to mink (Mustela vison) and European ferrets (Mustela putorius furo) was evaluated through dietary LC50 and reproduction tests. Twenty‐eight‐day LC50 tests with each species resulted in no overt signs of toxicity or mortalities, with the highest dietary concentrations being 2,520 ppm for mink and 4,536 ppm for ferrets. Mink were more sensitive to o‐cresol than were ferrets, based on feed consumption, body weight data and hematologic parameters. Both species routinely consumed in excess of the estimated oral LD50 in an average day's feed consumption at the highest dietary concentration. Mink in a reproduction test exhibited no significant adverse effects at dietary concentrations as high as 1,600 ppm over 6 months.

Experimental toxicity of sodium 2-ethylhexyl sulfate

Some aspects of the toxicity of the anionic surfactant sodium 2-ethylhexyl sulfate (Tergitol® anionic 08 2) were determined in rats, mice, rabbits, and dogs. The most toxic commercial samples found during 12 years had rat LD50 values of 5.61 ml/kg orally, 4.73 ml/kg sc, and 0.32 ml/kg ip. In the diet of rats for 90 days 1.25% of the commercial sample resulted in diffuse cloudy swelling of convoluted kidney tubules and central parts of the hepatic cords, while 0.25% was without effect. The highest dietary concentration (0.64%) studied for two years in rats and dogs was without effect.