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Biomedical subjects

J F Borzelleca

Publications and source records attributed to J F Borzelleca.

At least 19 recordsLinked to original sources
PubMed2006

A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats.

This study was conducted to evaluate the safety of l-theanine (Suntheanine) when administered as a dietary admixture to male and female Crl:CD (SD)GS BR rats at concentrations providing doses of 0, 1500, 3000 or 4000 mg/kg bw/day for 13 weeks. The study design was consistent with OECD Guideline 408 and USFDA Redbook II (1993) and GLP. There were no consistent, statistically significant treatment-related adverse effects on behavior, morbidity, mortality, body weight, food consumption and efficiency, clinical chemistry, hematology, or urinalysis. There were no consistent treatment-related adverse effects in gross pathology, organ weights or ratios or histopathology. The increased incidence of renal tubular cell adenomas in high-dose females only were not consistent with the characteristics of a renal carcinogen (due to early onset and low number of animals affected) but were more consistent with a genetic predisposition than with direct organ toxicity. The no-observed-adverse-effect-level (NOAEL) was 4000 mg/kg bw/day, the highest dose tested.

Animals↗
PubMed2005

Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy.

Glucosamine is widely used to relieve symptoms from osteoarthritis. Its safety and effects on glucose metabolism are critically evaluated in this review. The LD50 of oral glucosamine in animals is approximately 8000 mg/kg with no adverse effects at 2700 mg/kg for 12 months. Because altered glucose metabolism can be associated with parenteral administration of large doses of glucosamine in animals and with high concentrations in in vitro studies, we critically evaluated the clinical importance of these effects. Oral administration of large doses of glucosamine in animals has no documented effects on glucose metabolism. In vitro studies demonstrating effects of glucosamine on glucose metabolism have used concentrations that are 100-200 times higher than tissue levels expected with oral glucosamine administration in humans. We reviewed clinical trial data for 3063 human subjects. Fasting plasma glucose values decreased slightly for subjects after oral glucosamine for approximately 66 weeks. There were no adverse effects of oral glucosamine administration on blood, urine or fecal parameters. Side effects were significantly less common with glucosamine than placebo or non-steroidal anti-inflammatory drugs (NSAID). In contrast to NSAID, no serious or fatal side effects have been reported for glucosamine. Our critical evaluation indicates that glucosamine is safe under current conditions of use and does not affect glucose metabolism.

Administration, Oral↗
PubMed2005

A subchronic toxicity study in rats and genotoxicity tests with an aqueous ethylcellulose dispersion.

Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified release coating for beads, granules, non-pariels, drug crystals and tablets and for taste masking applications for drug products and dietary supplement products. A study was conducted to assess the toxicity of spray-dried Surelease when administered orally, via dietary admixture, to Sprague-Dawley CD rats (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period of at least 3 months. After 3 months of treatment, all rats scheduled for terminal sacrifice were killed and selected organs were weighed. Complete macroscopic examinations and histopathological evaluation of selected tissues were conducted on all animals. Neuropathological evaluations were performed on 5 animals/sex/group. No mortality occurred during the study. Clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalysis, functional observational assessments, motor activity, organ weights and ratios and macroscopic and microscopic observations did not reveal any significant, consistent, dose-dependent test article-related adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day, the highest dose tested. A series of genotoxicity tests were conducted with Surelease. Surelease showed no evidence of mutagenic activity in the bacterial reverse mutation test with and without metabolic activation and in the in vitro cell mutation assay under the experimental conditions employed. Surelease did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by gavage in the mouse micronucleus in vivo test procedure. These findings support the safety of Surelease for use as an excipient.

Animals↗
PubMed2003

Evaluation of the toxicity of polyvinylacetate phthalate in experimental animals.

Polyvinylacetate phthalate (PVAP) is used in the pharmaceutical industry as an ingredient in coating systems for oral solid dosage forms and in inks for monogramming capsules. PVAP has been evaluated in both sexes of several species in a number of toxicological studies including acute, repeated dosing, subchronic, chronic and reproductive and developmental. The acute oral toxicity is low in rats and mice (LD(50) > 8000 mg/kg body weight), although it appears to be more toxic in the dog. The gastrointestinal tract appears to be the target organ and effects seen (irritation, laxation, colitis with erosions and submucosal fibrosis in the dog and ulcers, polyps, and cecal wall thickening in rats) were dose dependent. There were no consistent treatment-related adverse effects on reproductive performance or development (not teratogenic). The no-observed-adverse-effect levels (NOAELs) ranged from 100 mg/kg body weight/day in the rabbit developmental toxicity study, to 500 mg/kg body weight/day in 24 month rat and dog studies, to 1000 mg/kg body weight/day in a one-generation reproduction study in the rat.

Animals↗
PubMed2003

Subchronic toxicity study in rats and genotoxicity tests with polyvinyl alcohol.

The potential systemic and neurotoxicity of polyvinyl alcohol (PVA) was assessed when fed in the diet to male and female Sprague-Dawley rats for 90 days at doses of 2000, 3500 and 5000 mg/kg/day. Control rats received untreated standard laboratory diet. Assessments included clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalyses, motor activity and functional observational battery evaluations and gross and microscopic pathology. The only test-article-related finding observed during the study was unformed stool with brown/black anogenital staining in rats fed 3500 and 5000 mg/kg/day. This finding was attributed to the high levels of test article being consumed and subsequently excreted in the stool. It was not accompanied by macroscopic or microscopic changes in these rats. No test-article-related changes were seen in mortality, ophthalmology, body weight and food consumption data, hematology, clinical chemistry, urinalysis data, functional observational assessments, motor activity, organ weight data and macroscopic and microscopic examinations. Doses of 2000, 3500 and 5000 mg/kg/day of PVA administered as a dietary admixture to male and female Sprague-Dawley rats for up to 90 days did not result in any adverse, toxicological effects. The no-observed-adverse-effect level (NOAEL) was determined to be 5000 mg/kg/day. PVA showed no evidence of mutagenic activity in the Ames test, mouse lymphoma assay and the mouse micronucleus test. (A critical evaluation of the available information on PVA will appear in a review to be published in Food and Chemical Toxicology 2003, 41, 319-326)

Administration, Oral↗
PubMed2003

Effects of polyvinyl alcohol administered in the diet to rats on fertility, early embryonic development, growth and development.

PVA was administered in the diet to male and female Sprague-Dawley rats (26/sex/group) at doses of 0, 2000, 3500 and 5000 mg/kg/day for two generations. The study design assessed gonadal function, estrous cycle, mating behavior, conception, gestation, parturition, lactation, weaning, and growth and development of F(1) and F(2) offspring. Parental rats were treated for 70 days prior to mating, throughout mating, gestation and lactation until sacrifice. Clinical observations, body weights and feed consumption were recorded routinely. Dietary concentrations were adjusted for each sex on a weekly basis except during gestation and lactation, to provide the intended mg/kg/day PVA levels. Pups were weighed routinely and weaned at 21 days of age prior to selection for the next generation. Unformed stool was noted predominately at the 3500 and 5000 mg/kg/day levels in P(0) and F(1) parental animals. This finding was attributed to the high levels of PVA being fed and subsequently excreted in the stool. Slight decreases in the mean body weights of P(0) males were noted at 2000 and 5000 mg/kg/day. Feed consumption was elevated at the 3500 and 5000 mg/kg/day doses in both generations but not during either lactation period. These increases generally were observed in a dose-related manner (g/kg/day), as a result of the large amount of PVA being consumed to maintain the caloric intake necessary for normal growth. There were no effects of PVA on P(0), F(1) male or female reproductive performance or pup survival, growth, organ weights, and macroscopic or microscopic observations at doses of 2000, 3500 and 5000 mg/kg/day. Therefore the no-observed-effect level (NOAEL) is 5000 mg/kg/day for both parental and offspring in this reproductive study.

Administration, Oral↗
PubMed2001

Comparison of AIN-76A and AIN-93G diets: a 13-week study in rats.

Either purified or cereal-based diets may be used for toxicity testing in rats. Purified diets have advantages in terms of flexibility of formulation to meet specific study objectives and also assurance of relatively low levels of contaminants (e.g. heavy metals and pesticides). The American Institute of Nutrition recommended that the widely used purified diet AIN-76A be replaced by two newer diets, AIN-93G (for use during rapid growth, pregnancy and lactation) and AIN-93M (maintenance diet). The present study compared AIN-76A and AIN-93G by feeding these diets for 13 weeks to male and female rats. A cereal-based diet was also included for reference purposes. The groups fed purified diets had higher serum cholesterol and triglyceride levels than the chow-fed group. An increased incidence and severity of renal tubular mineralization in the purified diet groups was not observed in this study (in contrast to other published studies where rats were fed AIN-76A). Several histopathologic observations, including eosinophilic gastritis and mucification of gastric glands of the glandular stomach, occurred at higher rates in the AIN-76A group than the other dietary treatments. Hepatocellular fatty changes occurred in the purified diet groups at a significantly higher rate than in the chow diet group. In conclusion, AIN-93G is an appropriate diet for use in rat safety evaluation studies.

Animal Feed↗
PubMed1999

Safety evaluation of ferrous bisglycinate chelate.

Ferrous bisglycinate chelate (Ferrochel) is a highly stable chelate that can be added to most foods. Data from human and animal studies indicate that the ferrous iron is readily bioavailable with fewer side-effects than the more commonly used iron salts. The acute oral LD50 for male and female Sprague-Dawley (S-D) rats is 2800 mg/kg body weight (560 mg/kg body weight iron [confidence limit (CL) 399-786] as the active ingredient). Male and female CD (Sprague Dawley-derived) rats were fed ferrous bisglycinate as a dietary admixture at doses of 0, 100, 250 and 500 mg/kg body weight/day. There were no biologically or statistically significant dose-related differences between the control and treated animals with respect to body weight gain, food consumption, food efficiency, behavioural effects, clinical chemistries, haematology, absolute and relative organ weights, or gross and microscopic findings. Hepatic non-heme iron concentrations were elevated, indicating that the ferrous iron had been absorbed. The no-observed-adverse-effect level (NOAEL) was 500 mg/kg body weight/day, the highest dose tested.

Animals↗
PubMed1998

Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data.

A critical and comprehensive review of the safety information on erythritol was undertaken. Numerous toxicity and metabolic studies have been conducted on erythritol in rats, mice and dogs. The toxicity studies consist of long-term feeding studies conducted to determine carcinogenic potential, intravenous and oral teratogenicity studies to determine the potential for effects on the foetus, oral studies in which erythritol was administered over one or two generations to determine the potential for reproductive effects, and studies in bacterial and mammalian systems to determine mutagenic potential. The majority of the safety studies conducted were feeding studies in which erythritol was mixed into the diet at concentrations as high as 20%. The metabolic studies in animals have shown that erythritol is almost completely absorbed, not metabolized systemically and is excreted unchanged in the urine. The safety studies have demonstrated that erythritol is well tolerated and elicits no toxicological effects. The clinical program for erythritol involved a series of single-dose and repeat-dose, short-duration studies which have been used to investigate the human correlates to the physiological responses seen in the preclinical studies. The clinical studies showed erythritol to be well tolerated and not to cause any toxicologically relevant effects, even following high-dose exposure. Erythritol administered orally to humans was rapidly absorbed from the gastrointestinal tract and quantitatively excreted in the urine without undergoing metabolic change. At high oral doses, urinary excretion accounted for approximately 90% of the administered dose with minimal amounts appearing in the faeces. A comparison of the human and animal data indicated a high degree of similarity in the metabolism of erythritol and this finding supports the use of the animal species used to evaluate the safety of erythritol for human consumption. It can be concluded, based on the available studies that erythritol did not produce evidence of toxicity.

Animals↗
PubMed1997

Assessment of cassia gum.

Cassia gum is approved for use in Europe by the Commission Directive (EEC No. E 499) and is listed in the Annex of the Council Directive (70/524/EEC) as a stabilizer (thickening and gelling agent) in the manufacture of canned pet foods (for cats and dogs). It is also approved for use in Japan and is listed as a food additive in The Ministry of Health and Welfare Announcement No. 160 (10 August 1995). A panel of experts in the areas of toxicology, pharmacology and food science was assembled to review the safety of cassia gum for use as a thickening agent in human and pet foods in the United States. The available data on cassia gum and structurally related gums demonstrate a lack of toxic effects in animals. This review is the basis for the consideration of cassia gum as generally recognized as safe (GRAS) under conditions of its intended use as a thickening agent in human and pet foods.

Animal Feed↗
PubMed1996

A proposed model for safety assessment of macronutrient substitutes.

Restriction of fatty foods is an effective means of reducing caloric intake and is consistent with public health goals to reduce the risk of chronic diseases. Compliance with low-fat diets is enhanced by the substitution of foods with the same organoleptic properties as fat, namely flavor, texture, and mouth-feel. Fat substitutes could replace a significant proportion of dietary fat and as such become macronutrient substitutes. The safety of these materials must be established prior to introduction into the food supply. As their use increases so will concerns about their safety. Appropriate methods of safety evaluation must be used. Traditional methods for the safety evaluation of food additives are inappropriate, since concentrations of the test materials high enough to provide a 100-fold safety factor cannot be used. An approach that recognizes the unique nature of macronutrient substitutes and includes the use of in vitro, whole-animal, and human studies and nutritional, physiological, and toxicological end points is proposed. Evaluations in humans are conducted early in this program but only when the animal data adequately support these studies. Human data will complement the animal data and may eliminate the need for some animal studies. The introduction of postmarketing surveillance will identify consumption patterns, associated adverse reactions, and potentially sensitive segments of the population and will ensure the continued safety of macronutrient substitutes.

Dietary Fats, Unsaturated↗
PubMed1996

A new approach to the safety assessment of pharmaceutical excipients. The Safety Committee of the International Pharmaceutical Excipients Council.

This article presents a set of proposed guidelines for the safety assessment of new pharmaceutical excipients. These guidelines were developed by the Safety Committee of the International Pharmaceutical Excipients Council and represent a new, scientifically based approach to establishing conditions for the safe use of proposed pharmaceutical excipients utilizing various routes of human exposure. They are based upon the best currently available toxicological science and have taken the deliberations of the International Conference on Harmonization into consideration. These guidelines were developed because there are no regulatory agency guidelines currently available which specifically address the toxicological testing of a material intended for use as an excipient in pharmaceutical preparations. Only materials which have been previously permitted for use in a pharmaceutical preparation or which have been permitted for use in foods may be considered safe under current practices. If implemented, these guidelines should expedite the review of a proposed new excipient by regulatory agencies.

Chemistry, Pharmaceutical↗
PubMed1996

Evaluation of the safety of sodium pectate as a food ingredient.

New potential uses of pectates in food products have recently stimulated interest in re-evaluating the information available concerning the safety of pectins and pectates as food ingredients. Data relevant to this re-evaluation have been obtained in rats in recent 14-day and 13 wk subchronic feeding studies with sodium pectate. Ames tests and other mutagenicity tests have been conducted with sodium pectate, bleached sodium pectate and mixed sodium/calcium pectate salts. These toxicological studies with pectates have provided further evidence of their safety, and support of the continued GRAS status of pectins and pectate salts.

Animals↗
PubMed1996

Serum creatine kinase does not predict ectopic pregnancy.

OBJECTIVE: To evaluate the discriminatory ability of maternal serum creatine kinase (SCK) as a test for ectopic pregnancy (EP). DESIGN: Serum creatine kinase concentrations were obtained prospectively from symptomatic patients being evaluated for early abnormal pregnancy. Serum creatine kinase concentrations from all patients and from a subset of these patients with maternal serum beta-hCG concentrations < 6,500 mIU/mL (conversion factor to SI unit, 1.00) were analyzed with descriptive statistics, receiver operator characteristic (ROC) curve analysis, and calculations of predictive values. SETTING: A university hospital emergency room. PATIENTS: Fifty-six patients with intrauterine gestations (25 with beta-hCG concentrations < 6,500 mIU/mL) and 23 patients with EP (20 with beta-hCG concentrations < 6,500 mIU/mL) were studied. RESULTS: For all patients and the subgroup with beta-hCG concentrations < 6,500 mIU/mL, mean SCK levels were not significantly different between ectopic and intrauterine gestations. For all patients and the subgroup with beta-hCG concentrations < 6,500 mIU/mL, the areas under the ROC curves did not demonstrate discriminatory ability of the SCK test. The highest positive predictive value of an elevated SCK for EP was 52% using the SCK concentration of 70 U/L, and this was seen in the subgroup of patients with beta-hCG values < 6,500 mIU/mL. CONCLUSIONS: Maternal SCK concentrations do not reliably predict EP.

Adult↗
PubMed1995

Safety assessment of polylactide (PLA) for use as a food-contact polymer.

This report constitutes a safety assessment of polylactide (PLA), a polymer of lactic acid intended for use in fabricating various food-contact articles. Migration studies were conducted on samples of the polymer following guidelines issued by the Food and Drug Administration. Potential migrants from PLA include lactic acid, lactide (the monomer), and lactoyllactic acid (the linear dimer of lactic acid). The studies were designed to model reasonable 'worst' case extraction situations when the polymer is used (a) in houseware articles for short and intermediate time periods at various temperatures and (b) in food-packaging materials. The limited migration observed during the trials represents no significant risk since migrating species are expected to convert to lactic acid, a safe food substance. It is concluded that PLA is safe and 'Generally Recognized As Safe' for its intended uses as a polymer for fabricating articles that will hold and/or package food.

Acetates↗