Certified LabDiet® 5K96 Advanced Protocol™ Verified Casein Diet 10 IF (5K96) is a commercial diet low in soy isoflavones developed for use in developmental and reproductive toxicity (DART) studies, especially those designed to detect endocrine disruptors. The objective of this study was to determine the incidences and severities of 5K96-associated renal lesions in control F0 and F1 cohorts of rats fed the 5K96 diet. Kidneys from control animals of four DART studies involving Sprague-Dawley rats fed the 5K96 diet, were evaluated microscopically. Mineralization and basophilic tubules were present in high incidence/severity in males and females compared to historical controls fed conventional diets. F1 cohorts were affected to a far greater degree than F0 cohorts, and females were affected more than males. Consideration of target tissue and mode of action should be given before automatically incorporating the 5K96 diet into DART study designs, and caution should be exercised when identifying and interpreting renal toxicity in the F1 cohorts of such studies.

Alkaline phosphatase (ALP) hydrolyzes a variety of monophosphate esters and plays an important role in phosphorus (P) metabolism. Several nutrients in food have been reported to affect intestinal ALP activity in animal models. Previous reports indicated that high levels of P or phosphate in diets decreased intestinal ALP activity in rats. Because potato starch contains considerable amounts of esterified P, unlike other starch-derived plants, we hypothesized that the feeding of potato starch would decrease ALP activity in the intestinal tract. Male Sprague-Dawley rats (7 weeks old) were fed 3 different types of diet containing 60% corn starch or 1 of 2 types of potato starch with different esterified P content for 1 or 5 weeks. Body weight and food intake of each rat were measured every day throughout the experimental periods. At the end of the feeding periods, the small intestine was removed to determine ALP activity in the mucosal tissues. Significant differences were observed in ALP activity in the small intestine between the 2 feeding periods, among the 4 segments of the small intestine, and among the 3 diet groups. Significant positive linear correlations between the amount of P derived from the starch and mucosal ALP activity were obtained in the jejunum and jejunoileum in rats after feeding for 5 weeks. We concluded, contrary to our hypotheses, that the ingestion of potato starch adaptively increases ALP activity in the upper part of the small intestine of growing rats in an esterified P content-dependent manner.

Two chick assays were conducted in an attempt to understand how 1alpha-hydroxylated cholecalciferol compounds [1,25-(OH)2 D3 and 1alpha-OH D3] function in chicks to improve utilization of phytate-bound phosphorus (P) and trace minerals. Mucosal tissue from chicks fed a P-deficient corn-soybean meal diet, with or without supplemental 1alpha-OH D3, was incubated with sodium phytate. Inorganic P (Pi) release from sodium phytate, a measure of mucosal phytase activity, was not influenced by 1alpha-OH D3 presence in the diet. Increasing doses of mucosal protein in tubes containing sodium phytate resulted in marked increases (P < 0.01) in Pi release, but 1alpha-OH D3 in the diet from which the duodenal mucosal tissue was obtained had no effect on Pi release. Similarly, addition of either 1alpha-OH D3 or 1,25-(OH)2 D3 directly to the incubation tubes had no effect on Pi production. Efficacy of supplemental 1alpha-OH D3 and phytase was also tested in cecectomized vs. sham-operated chicks that were fed P-deficient and cholecalciferol-adequate corn-soybean meal diets. Removal of the twin ceca was done in an attempt to remove much of the intestinal microbial activity, and in turn, much of the gut microbial phytase activity. Marked increases (P < 0.01) in bone ash occurred in response to phytase or 1alpha-OH D3 supplementation, and cecectomized birds responded to either addition in the same manner as sham-operated controls. The data suggest that the marked phytate-P releasing capacity of dietary 1alpha-OH D3 or 1, 25-(OH)2 D3 is not caused by an increased specific activity of intestinal phytase.

Experiments were conducted with pigs and rats to determine the availability of P in feeds. Initially, the availability of P in a soya-bean meal and field peas (Pisum sativum cultivar Early Dun) was assessed using a slope-ratio assay for grower pigs. Three different levels of either monosodium phosphate (MSP), soya-bean meal or field peas were added to a basal sucrose-soya-bean meal diet (2.5 g/kg P) to give three levels of P (3.0, 3.5 and 4 g/kg) for each source. The diets were offered for 35 d at three times maintenance energy requirements to female pigs initially weighing 20 kg live weight. Several bone variables and the ash and P concentration and retention levels in the empty body were used as criteria of availability. The responses to MSP were linear for all variables. However, responses to P in the test proteins, particularly soya-bean meal, were mostly non-linear, except for ash and P concentrations and retentions in the empty body. The estimates of P availability in the soya-bean meal and in the field peas were dependent on the criteria used to assess availability. Using bone variables as the criterion, the availabilities of P in soya-bean meal and field peas were approximately 0.17 and 0.38 respectively. Using ash or P concentrations or retentions in the empty body as the response criterion, the availabilities of P in soya-bean meal and field peas were 0.61 and 0.38 respectively. The mean retention values for P from MSP, soya-bean meal and field peas were 0.74, 0.33 and 0.21 respectively. Experiments were then conducted to define the conditions necessary for a slope-ratio assay for P availability with growing rats to determine if they could be used as a model to assess P availability for pigs. These experiments examined level of P in the diet, the effect of Ca:P ratio and criteria for assessing response (growth rate, feed intake, feed conversion ratio, bone ash and bone bending moment). The results indicated that a suitable range of dietary P for a slope-ratio assay in rats was 1.8-3.5 g/kg, with Ca:P ratio of between 1.3 and 6.2, and that ash content or bone bending moment of the femur bone were suitable criteria of response. However, using bone bending moment as the criterion of response, the availability of P in soya-bean meal was 0.81, which was considerably higher than the estimate with pigs.(ABSTRACT TRUNCATED AT 400 WORDS)