Depressed Body Weight Gain Research Articles

Comparative Effects of Phytosterols and Plant Oils on the Growth Depression in Chicks Fed Quillaja Saponin

To compare the effect of phytosterols (PS) and plant oils on the growth depression due to saponin, seven-day-old chicks were fed experimental diets for 10-12 days. A 0.6% Quillaja saponin in the diet depressed body weight gain, feed intake and gain/feed ratio. PS partly (0.1-0.2%) or completely (0.4 or 0.6%) counteracted the adverse effect of saponin. The effect of cholesterol (CHS) on saponin-fed chicks was compatible with that of PS. The alleviation in growth depression by both sterols was always accompanied by the increase in both feed intake and gain/feed ratio. PS also suppressed the elevated CHS concentrations in the serum and liver induced by the dietary CHS. Corn oil and coconut oil added to the saponin diet improved gain/feed ratio, but they failed to increase feed intake sufficiently. Consequently, the addition of plant oils was less effective than that of PS in alleviating the growth depressing-effect of saponin. Beef tallow, animal fat, showed the same effect on saponin-fed chicks as did plant oils. In addition, the beneficial effect of added corn oil or beef tallow disappeared when metabolizable energy of the diet containing oil or fat was equal to that of basal diet. Thus, the alleviative effect of plant oils seems to be attributed to the increase in the dietary energy rather than to the PS present in oils. In conclusion, increasing feed intake is necessary to improve the growth depression due to saponin.

Developmental toxicity studies in rats and rabbits with 3,5,6-trichloro-2-pyridinol, the major metabolite of chlorpyrifos.

3,5,6-Trichloro-2-pyridinol (TCP), the primary metabolite of chlorpyrifos and chlorpyrifos-methyl, was evaluated for potential developmental toxicity. Groups of 32-34 bred female Fischer 344 rats were given 0, 50, 100, or 150 mg TCP/kg/day by gavage on gestation days 6-15; the fetuses were evaluated on gestation day 21. Similarly, groups of 16 inseminated female New Zealand White rabbits were given 0, 25, 100, or 250 mg TCP/kg/day by gavage on gestation days 7-19, and fetuses were evaluated on gestation day 28. No clinical signs of toxicity attributed to TCP were noted in either species. In rats, at 150 mg/kg/day, maternal effects included slight decreases in feed consumption, significantly depressed body weight gain (25% relative to controls) resulting in significantly lower maternal terminal body weights, and increased relative liver weight. At 100 mg/kg/day, maternal body weight gain in rats was depressed approximately 22%. Among rabbits, maternal effects were limited to the group given 250 mg/kg/day, which lost an average of approximately 70 g during the treatment period (vs. 140 g in the controls). There were no effects on fetal weight or viability, nor were there significant increases in any fetal alteration in either species. A slightly higher (not statistically significant) than usual incidence of central nervous system anomalies occurred in rabbits, but these anomalies were found in both treated and control groups in this study as well as contemporaneous studies of unrelated compounds. This, and the fact that these anomalies were not seen with the parent compound, chlorpyrifos, suggest that their origin was spontaneous. Thus, TCP was not considered fetotoxic or teratogenic in either rats or rabbits, even at dose levels that produced maternal toxicity.

Amino Acid Supplementation of Low-Protein Broiler Diets: 2. Formulation on an Ideal Amino Acid Basis

In order to apply the ideal amino acid concept to broiler production, more knowledge is needed concerning low crude protein (CP), amino acid-supplemented diets. Three experiments were conducted to evaluate performance, carcass traits, and nitrogen balance of broilers fed low-CP diets supplemented with amino acids according to an ideal amino acid ratio. Marginal reductions in CP in both experiments resulted in equal body weight (BW) gain and feed conversion compared to birds fed the control diet, regardless of Thr supplementation. In contrast, severe CP reduction in both experiments resulted in a significant depression in BW gain and feed:gain. Although amino acid supplementation corrected the depression in BW gain and feed conversion in Experiment 1, it did not restore feed conversion in Experiment 2. A small reduction in dietary CP had little effect on carcass fat or lean yields, while further reductions in dietary CP, without amino acid supplementation, demonstrated inconsistent responses. Breast meat yield was unaffected by the further reduction in dietary CP, regardless of amino acid supplementation. Nitrogen excretion was dramatically reduced by a reduction in dietary CP by 1.2 percentage units but unexpectedly not when dietary CP was reduced by 2.7 percentage units.

Studies on semduramicin and nutritional responses. 1. Level and source of protein

An experiment was conducted to determine whether feeding semduramicin at recommended levels (25 mg/kg) would affect the broiler chicken's response to dietary protein; and to determine whether protein source (all vegetable, corn and soybean meal, vs 12% high animal protein ingredients) would affect the response to semduramicin. Semduramicin was fed to half of 1,584 male Ross x Ross broilers in floor pens during the growing phase (18 to 35 d). Three protein fortification levels were also fed with protein and amino acid minimum restrictions at 80, 100, and 120% of NRC (1994) recommendations. At 35 d, semduramicin was found to cause a slight growth depression in body weight gain only when low protein levels were fed (P = 0.051). After a 7-d withdrawal period, compensatory gains occurred (P = 0.006) such that there was no interaction effect of semduramicin by protein level for 42-d body weight (P = 0.75). Birds fed the diets containing high animal protein were slightly heavier than those fed control diets containing all-vegetable protein (2.40+/-0.02 vs 2.36+/-0.01 kg/bird; P = 0.059). Semduramicin feeding did not affect feed consumption (2.43+/-0.03 vs 2.40+/-0.02 kg per bird during the growing period when it was fed) so that overall feed conversion ratios were identical to two decimal places (1.90+/-0.02 vs 1.90+0.02). Neither did semduramicin affect feathering score or weight of the No. 8 primary feather, except that feather weight tended to be improved by semduramicin feeding with the diets containing ingredients high in animal protein (P = 0.067).

Liver Tumor Promoting Effects of Febantel in a Two-stage Hepatocarcinogenesis Model of Rats Using D-galactosamine and Diethylnitrosamine.

To examine whether febantel has a tumor promoting activity, a total of 50 male F344 rats, divided into five groups each consisting of 10 rats, were initiated with a single intraperitoneal injection of 100 mg/kg of diethylnitrosamine (DEN). Starting 1 week later, Groups 1, 2, and 3 were fed diet containing 2,500,500, and 0 ppm febantel, respectively, for 7 weeks. D-galactosamine (DGA) of 300 mg/kg was administered intraperitoneally at Weeks 1 and 6 of febantel treatment. The remaining two groups (Groups 4 and 5) were fed diet containing 2,000 or 0 ppm febantel without DGA treatment for 7 weeks. Animals in the DEN/DGA + 2,500 ppm group showed a significant depression of body weight gain, as compared to the DEN/DGA + 0 ppm group. Significant increases in the absolute and relative liver weights were observed in the DEN/DGA + 2,500 ppm and DEN +2,000 ppm groups in comparison with the corresponding controls. Similar increases in the relative liver weights were also seen in the DEN/DGA + 500 ppm group. Histologically, centrilobular hepatocellular hypertrophy was observed in the DEN/DGA + 2,500 ppm and DEN +2,000 ppm groups. Significant induction of CYP1A1/2, 2B1/2 and 4A1/3 was observed in the DEN/DGA + 2,500 ppm and DEN +2,000 ppm groups, as compared to the corresponding control groups. Similar induction of CYP1A2 and 2B1 was observed in the DEN/DGA + 500 ppm group. Significant increases in GST-P positive cells and/or mini-foci in the liver were observed in the DEN/DGA + 2,500 ppm group. These results suggest that febantel exerts liver tumor promotion potential. Since no increases in GST-P positive cells and/or foci in the liver were observed at the dose level of DEN/DGA + 500 ppm febantel, this dose is considered to be a no effect level for this promotion effect.

Effect of F-2 and T-2 fusariotoxins on experimental Cryptosporidium baileyi infection in chickens

The course of Cryptosporidium baileyi infection in chickens fed with different doses of fusariotoxins was compared with that of control groups. F-2 toxin levels of 0.187–1.5 mg kg −1 and T-2 toxin levels of 0.187–6.0 mg kg −1 were investigated. The experimental amimals were orally infected with 6 × 10 5 C. baileyi oocysts at 1 week of age. Total daily oocyst output was monitored by a quantitative method. Acquired immunity was tested at the age of 4 weeks, by ELISA and by a challenge infection with an equal number of oocysts, upon recovery from the primary infection. The results show that in chickens kept on the lower doses of F-2 and T-2 toxins, the parasite infection ran a similar course to that in the control groups, and the animals became resistant to re-infection. However, when higher doses (2.0–6.0 mg kg −1) of T-2 toxin were used, a depression of weight gain was observed with some other physiological parameters (PCV, weight of bursa, weight of thymus, skin thickness in PHA-P skin test) also indicating toxic effect and, simultaneously, the oocyst output decreased significantly and the patent period was slightly prolonged. Although certain modifications of the immune response could be revealed, the chickens became resistant to re-infection. Only early (1 week of age) parasite infection and 6 mg kg −1 T-2 toxin in the feed significantly depressed body weight gain and immunity.

Pathogenicity of chicken anaemia virus (isolate 10343) for young and older chickens

Summary One‐day‐old chicks, inoculated intramuscularly (i.m.) with the chicken anaemia virus (CAV) isolate 10343, showed depression of body weight gain and anaemia, particularly between days 14 and 21 post‐inoculation (p.i.)‐ The weights of thymus and bursa were substantially reduced compared to controls at days 14 and 21 p.i. The histological lesions detected in thymus, bursa, spleen and liver were similar in frequency at days 14 and 21 p.i. Eosinophilic intranuclear inclusion bodies, lymphocyte depletion, and focal necrosis were detected in the thymus, spleen, bursa and liver of more than 50% of the inoculated chicks at days 14 and 21 p.i. Focal necrosis and vacuolar degeneration in the liver, as well as apoptosis in different organs were more evident at days 14 and 21 p.i. Ten‐week‐old broiler breeders, inoculated i.m. with isolate 10343 showed pathological changes that were less severe than the changes shown by 1‐day‐old chicks. No anaemia could be detected in this group. However, severe thymus atrophy, and histological lesions in bursa, spleen, and liver, were also evident at days 14 and 21 p.i. in some of the inoculated birds. Viral detection by immunofluorescence using a monoclonal antibody revealed a wide distribution of the CAV isolate. CAV antigen was detected until day 21 p.i. in thymus, spleen, bursa and liver. According to the severity of the lesions shown by 1‐day‐old chicks, the length of the period in which CAV antigen could be detected in tissues, and the fact that CAV isolate 10343 was capable of inducing disease in 10‐week‐old chickens, it seems that this CAV isolate may be particularly virulent.

Effects of replacement of maize with dried leaves of sweet potato ( Hypomoea batatas) and perennial peanuts ( Arachis glabrata Benth) on the growth performance of finishing broilers

A total of 100 4-week-old unsexed Anak-2000 broiler chicks were used in a 4-week experiment to study the effect of replacing 200 or 300 g of maize kg −1 in the finisher diet with either sweet potato leaves ( Hypomoea batatas) or perennial peanut leaves ( Arachis glabrata Benth) on their growth rate and feed conversion ratio. The results revealed that the replacement of maize with sweet potato leaves significantly ( P < 0.05) depressed body weight gain. Perennial peanut leaves had the same adverse effect on weight gain when replacing 300 g maize kg −1. However, when 200 g maize kg −1 was replaced by perennial peanut leaves, weight gain by chicks was similar to that of the control treatment. The substitution of 300 g maize kg −1 by either sweet potato leaves or perennial peanuts significantly ( P < 0.05) increased feed conversion ratio. Therefore, the replacement of maize by either sweet potato or Arachis glabrata leaf meal does not seem justified under the conditions of this experiment.

Reproductive and developmental toxicity studies of calcipotriol (MC903): (1)--A fertility study in rats by subcutaneous administration

Calcipotriol (MC903), an anti-psoriasic agent, was given subcutaneously at dose levels of 1, 5 and 25 micrograms/kg/day during the pre-pairing period (9 weeks prior to pairing in males and 2 weeks prior to pairing in females) and the pairing period to male and female rats and in the early stage of pregnancy (day 0 through 7 of gestation) to female rats, and the effects of the test compound on male and female reproductive performance and fetal development were evaluated. 1. In the male 25 micrograms/kg group, opacity of the eyeball surface was observed, and depression of body weight gain, and decreases of body weight and food consumption, and increases in the weight of the kidney were statistically significant in comparison with vehicle controls. 2. In the female 25 micrograms/kg group, depression of body weight gain and food consumption were statistically significant in comparison with vehicle controls. 3. No changes in parameters of reproductive performance were seen in any dosed groups. 4. No changes in parameters of implantation performance were seen. There were no treated-related abnormalities in fetal mortality, weights of fetuses, and external, visceral and skeletal examinations. Based on there results, it is considered that in the present study the no-toxic dose levels of MC903 were 5 micrograms/kg/day for parents, 25 micrograms/kg/day for reproductive performance and fetal development.

Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice.

Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS.

Inhalation Teratology and Reproduction Studies with 1, 1-Dichloro-2,2,2-Trifluoroethane(HCFC-123)

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and two-generation inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F1 generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F1 generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern. Since weight gain for the F1 animals was normal following weaning, this depression of body weight gain may be related to the depression of serum triglycerides. In addition, liver weights of the adult rats exposed to levels of 100 ppm and higher of HCFC 123 were higher than controls, histological examination revealed only hepatic enlargement and vacuolation. It was concluded that exposure to HCFC 123 did not cause reproductive effects although it did effect the body weight gain of the offspring during lactation.

Developmental Toxicity of Amesergide Administered by Gavage to CD Rats and New Zealand White Rabbits

Developmental Toxicity of Amesergide Administered by Gavage to CD Rats and New Zealand White Rabbits. Kelich, S. L., Meade, P. L., II, and Seyler, D. E. (1995). Fundam. Appl. Toxicol. 27, 247-251. Amesergide is a selective serotonin 5-HT 1C/2 receptor antagonist being developed for the treatment of depression. The potential developmental toxicity of amesergide was evaluated in CD rats and New Zealand white rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation Days 6-17 and 6-18, respectively. Doses for rats were 0, 3, 10, and 30 mg/kg; doses for rabbits were 0, 0.2, 2, and 15 mg/kg. Cesarean sections were performed on rats and rabbits on Gestation Days 20 and 28, respectively. In rats, maternal effects expressed as depression of body weight gain and food consumption were observed at the 30 mg/kg dose level. Fetal viability and morphology were not affected at any dose level. Fetal weight was depressed at the 30 mg/kg dose level. The no-observed-effect level (NOEL) in the rat was 19 mg/kg. In rabbits, maternal effects expressed as a decrease in food consumption occurred at the 2 and 15 mg/kg dose levels; weight gain was depressed at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. The NOELs for maternal and developmental effects in the rabbit were 0.2 and 15 mg/kg, respectively.

Dietary Protein Quality Alters Ornithine Decarboxylase Activity but Not Vitamin B-6 Nutritional Status in Rats1

Weanling male rats were fed diets that varied in protein quality (casein or wheat gluten) and vitamin B-6 (0.0, 0.5, 1.0 and 1.5 mg pyridoxine HCl/kg diet) to test the hypotheses that low protein quality would depress vitamin B-6 nutritional status and that activity of ornithine decarboxylase (ODC) would be a sensitive functional indicator of vitamin B-6 nutritional status. The wheat gluten diet depressed body weight gain -17% at higher vitamin B-6 levels, as expected. However, vitamin B-6 nutritional status was not worse in gluten-fed compared with casein-fed groups, as evidenced by static measures (B-6 vitamer concentrations in plasma and tissues) and a functional indicator (tryptophan load test). The activity of ODC (holo- and total) in liver, kidney and small intestine did not vary significantly at the three higher levels of vitamin B-6 intake. In groups fed casein, total ODC activity in these tissues was two- to fivefold higher in rats fed diets containing 0.0 mg vitamin B-6/kg compared with higher B-6 levels, without corresponding differences in ODC mRNA abundance in liver and kidney. Concentrations of B-6 vitamers (except pyridoxal phosphate in plasma) increased linearly with dietary vitamin B-6 in plasma, liver, kidney and intestine. These data suggest that low quality protein fed as wheat gluten suppresses growth but not vitamin B-6 nutritional status, and that ODC activity is not a sensitive functional indicator of marginal vitamin B-6 status.

Short-term inhalation toxicity of methanol, gasoline, and methanol/gasoline in the rat.

Four- to five-week-old male and female Sprague Dawley rats were exposed to vapors of methanol (2500 ppm), gasoline (3200 ppm), and methanol/gasoline (2500/3200 ppm, 570/3200 ppm) six hours per day, five days per week for four weeks. Control animals were exposed to filtered room air only. Depression in body weight gain and reduced food consumption were observed in male rats, and increased relative liver weight was detected in rats of both sexes exposed to gasoline or methanol/gasoline mixtures. Rats of both sexes exposed to methanol/gasoline mixtures had increased relative kidney weight and females exposed to gasoline and methanol/gasoline mixtures had increased kidney weight. Decreased serum glucose and cholesterol were detected in male rats exposed to gasoline and methanol/gasoline mixtures. Decreased hemoglobin was observed in females inhaling vapors of gasoline and methanol/gasoline at 570/3200 ppm. Urine from rats inhaling gasoline or methanol/gasoline mixtures had up to a fourfold increase in hippuric acid, a biomarker of exposure to the toluene constituent of gasoline, and up to a sixfold elevation in ascorbic acid, a noninvasive biomarker of hepatic response. Hepatic mixed-function oxidase (aniline hydroxylase, aminopyrine N-demethylase and ethoxyresorufin O-deethylase) activities and UDP-glucuronosyltransferase activity were elevated in rats exposed to gasoline and methanol/gasoline mixtures. Histopathological changes were confined to very mild changes in the nasal passages and in the uterus, where decreased incidence or absence of mucosal and myometrial eosinophilia was observed in females inhaling gasoline and methanol/gasoline at 570/3200 ppm. It was concluded that gasoline was largely responsible for the adverse effects, the most significant of which included depression in weight gain in the males, increased liver weight and hepatic microsomal enzyme activities in both sexes, and suppression of uterine eosinophilia. No apparent interactive effects between methanol and gasoline were observed.

Intravenous single dose toxicity of iodixanol, a new nonionic iso-osmolar contrast medium, in mice, rats and monkeys

The single-dose intravenous toxicities of iodixanol, a new nonionic iso-osmolar contrast medium, were investigated in mice, rats and monkeys. The LD50 values were estimated to be 17.9 gI/kg for male mice and 16.2 gI/kg for female mice, 18.8 gI/kg for male rats and 22.0 gI/kg for female rats, and more than 10.0 gI/kg for monkeys. There was no marked sex difference in mice or rats, nor any significant difference observed between these two rodent species. Decrease in spontaneous locomotor activity, ptosis, respiratory depression and abdominal posture were observed in many mice and rats. These signs disappeared mostly by 8 days after dosing in surviving animals. Death occurred between immediately and 4 days after dosing in mice, and between immediately and 14 days after dosing in rats. Transient depression of body weight gain was observed in the surviving mice and rats by 7 days after dosing. Histological examinations revealed congestion or hemorrhage in the renal medulla, vacuolation or necrosis of the renal proximal tubular epithelium in mice and rats that died and vacuolation of the renal proximal tubular epithelium in surviving rats. There were no significant treatment-related changes in the laboratory and pathological examinations in monkeys.

Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat.

In a chronic toxicity study in the rat, bidisomide administered as a dietary admixture produced a dose-related lowering of reticulocytes and leucocytes. Plasma alanine aminotransferase activity was increased at 300 mg/kg and decreased at 900 mg/kg. The potential mechanisms of these effects were investigated by comparing the responses in groups of male Sprague-Dawley rats receiving a control diet, or 300 or 1200 mg/kg/day bidisomide. Subsets of these groups were co-treated subcutaneously with folinic acid or with a vitamin B1, B6, B12 complex. Subsets of control and 300 mg/kg groups were maintained on a 20-25% feed restriction regimen for 3 months, to mimic the depression in body weight gain observed in animals receiving 1200 mg/kg. Body weight gains were significantly reduced at 1200 mg/kg and in all feed-restricted animals. Plasma and liver alanine aminotransferase (ALT) and plasma aspartate aminotransferase (AST) levels were also reduced at this dose level. At 300 mg/kg, plasma transaminases, glutamate dehydrogenase (GLDH) and sorbitol dehydrogenase (SDH) activities were increased. These changes were prevented in animals receiving folinic acid supplementation. Plasma glucose, triglycerides, and unsaturated and total iron binding capacities were decreased, while plasma iron levels tended to increase, mainly at the high dose. Vitamin supplementation prevented a decrease in reticulocyte counts at 300 mg/kg. Bidisomide increased urinary formimino-glutamic acid (FIGLU) excretion but did not affect methylmalonic acid (MMA) or taurine excretion. The effect on FIGLU at 1200 mg/kg was prevented by folinic acid co-treatment. Absolute liver weight was lowered at both dose levels and in feed-restricted animals. However, the relative liver weights were unaffected. Thymidine kinase and thymidylate synthase activity of the bone marrow cells were not altered by the bidisomide treatment. Except for the increase in plasma transaminase, GLDH and SDH levels at 300 mg/kg, changes in clinical chemistry parameters are considered to result mainly from nutritional restrictions. Changes in hematologic parameters appear to be related to the combination of decreased feed consumption (leukocytes) and decreased availability or utilization of folates (reticulocytes). This alteration, however, did not affect DNA synthesis in bone marrow. The prevention by folinic acid, but not by feed restriction, of the elevation of liver enzymes at 300 mg/kg is an intriguing, yet unexplained finding. There was no evidence that bidisomide affected B6 and B12 availability.

Effects of dietary corticosterone and trilostane on growth and skeletal muscle protein turnover in broiler cockerels

1. The effects of dietary corticosterone and trilostane, an inhibitor of glucocorticoid synthesis, on: growth, rates of synthesis and breakdown of skeletal muscle protein, and content of abdominal fat were studied in broiler chickens. 2. Dietary corticosterone (5, 10 or 20 mg/kg) depressed body weight gain and increased abdominal fat content in a dose-dependent manner while dietary trilostane (1.4 or 7.0 mg/kg) had no effect. 3. The rate of protein breakdown in skeletal muscle estimated from N tau-methylhistidine excretion was increased in a dose-dependent manner by dietary corticosterone but it was decreased by trilostane. 4. The rate of skeletal muscle protein synthesis was not affected by corticosterone although it was decreased by trilostane. 5. Plasma corticosterone concentration was increased in a dose-dependent manner by dietary corticosterone and decreased by treatment with 7 mg trilostane/kg diet. 6. The results indicate that higher concentrations of plasma corticosterone increase protein breakdown in skeletal muscle but do not affect muscle protein synthesis while both the rates of synthesis and breakdown are decreased when plasma corticosterone concentration is reduced.

Developmental Toxicology Studies of Vancomycin Hydrochloride Administered Intravenously to Rats and Rabbits

Developmental Toxicology Studies of Vancomycin Hydrochloride Administered Intravenously to Rats and Rabbits. Byrd, R. A., Gries, C. L., and Buening, M. K. (1994) Fundam. Appl. Toxicol. 23, 590-597. Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis. Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin. Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively. In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group. Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin. Mater nal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively. Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus.

Effects of tri- n-butyl phosphate on pregnancy in rats

A teratological study was carried out on the plasticizer tri- n-butyl phosphate (TBP). Pregnant Wistar rats were treated orally on days 7–17 of gestation with TBP at 0, 100, 200, 400 or 800 mg/kg/day in the dose-finding study and 0, 62.5, 125, 250 or 500 mg/kg/day in the subsequent teratological study. Caesarean sections were performed on day 20 of gestation. In the dose-finding study, all of the pregnant rats were killed by the treatment with TBP at 800 mg/kg/day. In the teratological study, salivation and depression of body weight gain, adjusted body weight gain and food consumption were observed at the higher doses of TBP. There were no significant differences between the groups in the incidence of dead or resorbed foetuses, the number of living foetuses and the body weights of living foetuses of both sexes. The incidence of rudimentary lumbar rib increased significantly at 500 mg/kg/day. There were two cases of malformation: a foetus with deformity of fore- and hind-limbs at 400 mg/kg/day in the dose-finding study and conjoined twins exhibiting three fore-limbs and four hind-limbs at 125 mg/kg/day in the teratological study. These malformations were rare in the background data of teratology, and the incidence of foetuses with malformations was not increased significantly. Therefore, TBP was considered not to be teratogenic in this study.

Evaluation of Subchronic (13 Week), Reproductive, and in Vitro Genetic Toxicity Potential of 2-Ethylhexyl-2-cyano-3,3-diphenyl Acrylate (Octocrylene)

Evaluation of Subchronic (13 Week), Reproductive, and in Vitro Genetic Toxicity Potential of 2-Ethylhexyl-2-cyano-3,3-diphenyl Acrylate (Octocrylene). Odio, M. R., Azri-Meehan, S., Robison, S. H., and Kraus, A. L. (1994). Fundam. Appl. Toxicol. 22, 355-368.Use of 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Octocrylene) in commercial sunscreen products has increased considerably in recent years. To support larger scale human exposure to this compound, additional toxicological information was needed in several key areas. The present studies evaluated subchronic toxicity, developmental toxicity, and in vitro genotoxic potential of Octocrylene. In the subchronic study, male and female New Zealand white (NZW) rabbits treated topically with concentrations of octocrylene up to 534 mg/kg/day for 13 weeks showed slight to moderate dose-dependent skin irritation that correlated positively with a mild depression in body weight gain. Lack of associated histopathologic or clinical hematology abnormalities suggested that the body weight effect probably reflected a nonspecific response to topical irritation. In percutaneous developmental toxicity studies, NZW does were treated topically with Octocrylene at levels up to 267 mg/kg/day on Days 6 through 18 of gestation. Body weight gain, food consumption, and all maternal, reproductive, and offspring parameters evaluated were comparable between Octocrylene-treated and control animals. In the oral developmental toxicity assay, female CD-1 mice received oral doses of Octocrylene up to 1000 mg/kg/day on Days 8-12 of gestation. No evidence of maternal or developmental toxicity was seen at any dose tested. Genotoxicity was evaluated in vitro using the Chinese hamster ovary cell assay to assess clastogenicity and the mouse lymphoma cell assay to assess forward gene mutations. Octocrylene did not induce any significant increase in genotoxicity. This evaluation of toxicological potential supports the use of Octocrylene as a human photoprotectant.