Depressed Body Weight Gain Research Articles

Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide

A chronic toxicity and carcinogenicity study was conducted by feeding diets containing 80, 200 or 500 ppm total bromine following fumigation with methyl bromide, a diet containing 500 ppm potassium bromide, or a basal diet alone to groups of 60 male and 60 female Fischer (F344) rats for up to 2 yr. Ten males and ten females from each group were killed after wk 52 and 104 for urinalysis, haematology, blood biochemistry and pathology. Rats that were killed in extremis or found dead during the study and all rats that survived to the end of the study were also subjected to pathological examinations. In rats fed the diets fumigated with methyl bromide there were no marked toxic changes, except for a slight depression of body-weight gain from wk 60 onwards in males of the 500-ppm group, and tumour incidence was unaffected. Rats given a diet containing potassium bromide did not show any treatment-related changes. It was concluded that residues of up to 500 ppm total bromine in diets fumigated with methyl bromide are not carcinogenic in F344 rats of either sex and that the maximum no-effect level is 200 ppm (6.77 mg total bromine/kg body weight/day) in males. The maximum no-effect level could not be determined in females.

Vitamin B-6 Requirement of Growing Kittens

Two experiments were conducted to determine the vitamin B-6 requirement for growing kittens. Ten kittens were divided into two groups and given a purified diet containing 8.0 mg pyridoxine (PN)/kg diet (+PN) or a PN-free diet (-PN) for 11 wk. Daily body weight gain, food intake, weekly plasma free amino acids, plasma B-6 vitamers, urinary oxalate excretion, hemoglobin (Hb) and hematocrit were measured. Kittens fed a -PN diet had depressed body weight gain, food intake, plasma pyridoxal phosphate (PLP) and pyridoxal (PL), Hb and hematocrit, and had elevated urinary oxalate, plasma tyrosine and plasma cystathionine. In a second experiment, 24 kittens were given a -PN diet for 45 d to deplete their body reserves. The kittens were then divided into six groups of four kittens each and given a purified diet containing either 0.5, 1.0, 2.0, 3.0, 4.0 or 8.0 mg PN/kg diet for 46 d. Following supplementation, positive responses in body weight gain, PLP, Hb and hematocrit, and decreased urinary oxalate excretion, plasma tyrosine and plasma cystathionine occurred in all groups except those fed 0.5 mg PN/kg diet. At the end of the repletion period, kittens fed 1.0 mg PN/kg diet had lower body weight gain, higher plasma tyrosine and cystathionine, slower rate of decrease in urinary oxalate, and lower values for Hb, hematocrit and PLP than did the kittens from groups fed 2.0-8.0 mg PN/kg diet. These findings indicate that the dietary requirement for PN is greater than 1.0 mg/kg diet, but 2.0 mg PN/kg diet is adequate for growing kittens given a 35% casein diet.

Thirteen-week toxicity study of n-hexane in B6C3F 1 mice after inhalation exposure

B6C3F 1 mice were exposed to n-hexane 6 h/day, 5 days/week for 13 weeks at concentrations of 0, 500, 1000, 4000, and 10 000 ppm and at 1000 ppm 22 h/day, 5 days/week for 13 weeks (1000C group). Toxicological endpoints assessed included clinical signs, body and organ weight changes, gross and histopathology, neuropathology, and a battery of neurobehavioral tests. All mice survived the treatment. Exposure-related effects of n-hexane included sneezing at 10 000 ppm and body weight gain depression at 1000C and 10 000 ppm. Histopathologic changes included mild inflammatory, erosive and regenerative lesions in the olfactory and respiratory epithelium of the nasal cavity at 1000C, 4000, and 10 000 ppm. The only neurobehavioral parameter affected was a decrease in locomotor activity in female mice at 1000C and 10 000 ppm. In teased fiber preparations of tibial nerve, paranodal axonal swellings were observed at 1000C or at 10 000 ppm, but not in the control groups. The severity of the peripheral nerve lesion was mild. These studies show that n-hexane has minimal toxicity to the nervous system and respiratory system of mice.

Toxicity studies of amphetamine sulfate, ampicillin trihydrate, codeine, 8-methoxypsoralen, α-methyldopa, penicillin VK and propantheline bromide in rats and mice

Thirteen-week toxicity studies in F344/N rats and B6C3F 1 mice were conducted to determine general toxicity and target organ toxicity with amphetamine sulfate, ampicillin trihydrate, codeine, 8-methooxypsoralen, α-methyldopa sesquihydrate, penicillin VK, and propantheline bromide. This paper discusses the toxicity observed; use of the toxicity data to set dose levels for subsequent 2-year studies; and comparison of dose levels administered to rodents with doses used in the treatment of human disease. Drugs were administered orally in the feed or by gavage. The lowest doses in the 13-week studies were comparable to therapeutic doses in man on a mg/m 2 (body surface area) basis or 5–10 times doses used in man on a mg/kg body weight basis. Little toxicity was seen at the low dose level with ampicillin, penicillin VK, 8-methoxypsoralen or propantheline bromide. At higher doses, target organ toxicity seen included the urinary bladder in male rats after propantheline bromide; the glandular stomach in rats and mice after penicillin VK; the liver and adrenals in rats after 8-methoxypsoralen; and the kidney in mice and rats after α-methyldopa. After amphetamine, codeine, or ampicillin administration, no target organ toxicity was seen in rats or mice, even at doses which caused body weight gain depression. The high doses chosen for subsequent 2-year studies were within 10 times human dose levels when compared on a mg/m 2 body surface area.

Reproduction study of propiverine hydrochloride (4)--perinatal and postnatal study in rats by oral administration

A perinatal and postnatal study was performed in Sprague-Dawley rats by oral administration of propiverine hydrochloride (P-4) at dose levels of 0 (control), 2, 10 and 50 mg/kg/day to dams from day 17 of pregnancy to day 21 after delivery. Twenty two or twenty four dams in each group were allowed to deliver for the postnatal examination of their offspring. In dams, the dose of 50mg/kg caused toxic signs consisting of mydriasis, salivation and rale. One dam of this group showed piloerection, low body temperature, blanching of extremity and auricle, and emaciation associated with marked prolongation of delivery. Body weight gain of the dams was retarded in the 50 mg/kg group throughout the administration period. Food and water intakes were reduced in the 50mg/kg group. In gross pathology of the dam that showed prolonged delivery, the spleen and thymus were moderately or severely atrophied and the adrenal was moderately enlarged. The viability index of the offspring on day 4 was reduced in the 50mg/kg group. Body weight of pups slightly decreased in the 50mg/kg group during sucking and rearing periods. Absolute weights of some organs of the three-week aged offspring were reduced due to attributable depression of body weight gain. However, P-4 had no adverse effect on the postnatal development such as emotionality, motor activity, learning ability or reproductive performance. The results suggest that the non-effective dose level of P-4 is 10mg/kg/day in maternal animals and offspring.

Toxic responses in F344 rats and B6C3F 1 mice given roxarsone in their diets for up to 13 weeks

Thirteen-week toxicity studies were conducted in groups of 10 F344 rats and B6C3F 1 mice of each sex fed roxarsone at 0, 50, 100, 200, 400, or 800 ppm in the diet. Arsenic levels in blood, urine, kidneys, and liver of rats were measured in additional animals of each sex dosed with 100 or 400 ppm roxarsone. Compound-related mortality occurred in both sexes of rats at 800 ppm and mice at 800 and 400 ppm. Significant body weight gain depression occurred in both sexes of rats at 200, 400, and 800 ppm and mice at 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats and mice at 800 ppm. Lesions associated with roxarsone administration were noted only in the kidney of rats and were characterized by tubular necrosis and mineralization at the corticomedullary junction. Arsenic levels in urine, blood, liver, and kidneys increased over time and were directly proportional to the level of roxarsone in feed. These levels were > 6 times higher in rats than in mice and were about 2 times higher in males than in females. The no-observable-effect level for roxarsone toxicity was estimated at 100 ppm for rats and 200 ppm for mice. No hematology or clinical chemistry effects were found in rats or mice of either sex.

Early Protein Undernutrition and Subsequent Realimentation in Turkeys.: 1. Effect of Performance and Body Composition

Male and female Large White Nicholas turkeys were fed corn and soybean meal diets for 24 and 20 wk, respectively. Control and low protein (75% of control in protein and 66% of control in lysine and methionine) diets were fed during 0 to 6 wk of age. Thereafter, both groups received the control diet. Body composition of turkeys was determined at 0, 2, 4, 6, 8, 12, 16, 20, and 24 (males), and at 0, 2, 4, 6, 8, 11, 14, 17, and 20 (females) wk of age.Compared with controls, undernourished turkeys had depressed body weight gain, lower feed intake, poorer feed efficiency, reduced carcass protein, increased carcass fat, and better efficiency of protein retention at 6 wk of age. During realimentation (after 6 wk of age), undernourished turkeys increased average daily feed consumption to that of controls and showed increased weight gains. By 24 and 20 wk of age, weights of undernourished male and female turkeys were no longer different from the weights of their respective controls. Feed efficiency of undernourished turkeys was better than that of controls during realimentation. Differences in body composition of undernourished and control turkeys were no longer evident after realimentation.

Experimental T-2 toxicosis in swine following inhalation exposure: Clinical signs and effects on hematology, serum biochemistry, and immune response

Nine- to ten-week-old, male castrated, specific pathogen-free derived pigs, weighing 34 to 42 kg, were exposed to a T-2 toxin aerosol (390 μg/liter, 1.5 μ M mass median aerodynamic diameter) for a time period which allowed an amount equivalent to 8 mg/kg to be nebulized (six pigs). Control animals (five pigs) were exposed to an equivalent amount of the nebulized vehicle. Pigs were immunized subcutaneously with sheep red blood cells on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic studies. Pigs were closely observed, and daily rectal temperatures and weekly weights were measured. The T-2-treated pigs vomited and exhibited cyanosis, anorexia, lethargy, lateral recumbency, slightly elevated rectal temperature, and depressed body weight gain. The lymphocyte count decreased while the neutrophil count increased. The concentrations of total serum protein and hemoglobin declined. There was a marked increase in serum alkaline phosphatase activity on Day 1, followed by a marked and persistent decrease. Mitogen-induced (Con A, PHA, and PWM) blastogenic responses of peripheral blood mononuclear cells and hemagglutination titers to SRBC were also transiently decreased. Thus, inhalation exposure of pigs to a sublethal dose of T-2 toxin caused clinical signs of toxicity and adverse effects on clinical pathologic parameters and immune responses; however, most of these effects were short-lived. The changes described in our study resemble those reported in pigs given T-2 toxin by intravascular injection.

Teratology studies of compound LY171883 administered orally to rats and rabbits

The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20 Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.

Experimental T-2 Toxicosis in Swine following Inhalation Exposure: Clinical Signs and Effcts of Hematology, Serum Biochemistry and Immune Respones

Nine- to ten-week-old, male castrated, specific pathogen-free derived pigs, weighing 34 to 42 kg, were exposed to a T-2 toxin aerosol (390 micrograms/liter, 1.5 microM mass median aerodynamic diameter) for a time period which allowed an amount equivalent to 8 mg/kg to be nebulized (six pigs). Control animals (five pigs) were exposed to an equivalent amount of the nebulized vehicle. Pigs were immunized subcutaneously with sheep red blood cells on Days 0 and 21. Whole blood and serum samples were taken periodically for clinical pathologic and immunologic studies. Pigs were closely observed, and daily rectal temperatures and weekly weights were measured. The T-2-treated pigs vomited and exhibited cyanosis, anorexia, lethargy, lateral recumbency, slightly elevated rectal temperature, and depressed body weight gain. The lymphocyte count decreased while the neutrophil count increased. The concentrations of total serum protein and hemoglobin declined. There was a marked increase in serum alkaline phosphatase activity on Day 1, followed by a marked and persistent decrease. Mitogen-induced (Con A, PHA, and PWM) blastogenic responses of peripheral blood mononuclear cells and hemagglutination titers to SRBC were also transiently decreased. Thus, inhalation exposure of pigs to a sublethal dose of T-2 toxin caused clinical signs of toxicity and adverse effects on clinical pathologic parameters and immune responses; however, most of these effects were short-lived. The changes described in our study resemble those reported in pigs given T-2 toxin by intravascular injection.

Research Note: Effects of Dietary Butylated Hydroxyanisole and Cysteine on Toxicity of Lathyrus odoratus to Broiler and Japanese Quail Chicks

The effect of .75% dietary butylated hydroxyanisole (BHA) and 1% cysteine on the toxicity of Lathyrus odoratus seed to Japanese quail and broiler chicks was examined. In both species, the feeding of Lathyrus seed as a component of a complete diet depressed (P<.05) body weight gain and feed intake. Typical signs of lathyrism, including ruffled feathers, enlarged hocks, curled toes, ataxia, leg paralysis, and mortality, were observed. Neither BHA nor cysteine exerted protective effects against the lathyrogenic effects. As assessed by mortality, these additives appeared instead to potentiate Lathyrus toxicity.

Deficient Amino Acids in Protein of Dehulled Soybean Meal for Young Turkeys

Two 12-day experiments were conducted with Large White turkeys to determine which amino acids are deficient in a diet containing dehulled soybean meal as the sole source of protein. A 22% protein basal diet composed of 43.3% glucose monohydrate, 45.4% dehulled soybean meal, .5% DL-methionine, 6% stabilized fat, and added minerals and vitamins served as the negative control. Two positive control diets were formed by substituting either 16.5% dehulled soybean meal or a mixture containing amounts of essential amino acids equivalent to those in the added dehulled soybean meal in place of an equal amount of glucose monohydrate in the basal diet. Nine additional diets were formed by removing one or more amino acids from the mixture. Each of the 12 diets in a block design was fed to two pens of males and two pens of females with 8 birds per pen from 7 to 19 days of age in each experiment.Average body weight gain of poults fed the 22% protein diet with added amino acids approached that of poults fed the 30% protein diet (288 vs. 300 g, respectively). Removal of the amino acid mixture from the 22% protein diet depressed body weight gain by 19.0%. Depressions of 19, 16, 11, 7, and 6% in body weight gains resulted from the removal of valine, threonine, lysine, phenylalanine (or tyrosine or glycine), and isoleucine, respectively. A decrease of 5% was required for significance (P≤.05). When evaluated by this deletion technique, effects of valine and threonine deficiency were more pronounced than effects of lysine deficiency in dehulled soybean meal for young turkeys.

Effect of exogenous corticosterone in genetically fat and lean chickens

1. The effects of daily injections of corticosterone (1 or 5 mg/bird) on growth, fat deposition, liver lipid and plasma concentrations of uric acid, glucose, insulin and growth hormone were studied using genetically selected lines of fat (FL) and lean (LL) chickens. 2. Both doses of corticosterone depressed body weight gain and increased the liver lipid and the abdominal fat to the same extent in both lines. 3. In both lines, corticosterone caused a dose-dependent increase in the plasma concentrations of uric acid, glucose and insulin in the fasted and refed states. 4. In untreated birds, plasma concentrations of growth hormone (GH) were slightly higher in FL than in LL chickens and slightly decreased during refeeding. The response was not modified by injection of 1 mg corticosterone. Injections of 5 mg decreased plasma GH in both lines in the fasting state and in LL chickens during refeeding. In contrast, the same dose increased GH in FL chickens during refeeding. This contradiction remains unexplained. 5. The results suggest that corticosterone sensitivity is not involved in difference of fattening between FL and LL chickens.

Effect of unbalanced diets on incorporation of δ-aminolevulinic acid into cytochrome P-450

The in vivo syntheses of two liver microsomal cytochromes P-450 PB 3a, P-450 UT 50 [(1987) Eur. J. Biochem., submitted] ( M r 50 000, 52 000) have been estimated by measuring the specific activity 2 h after i.p. administration of δ-[ 3H]aminolevulinic acid to male Sprague Dawley rats. The animals were fed either a standard rat chow (5% lard, 22% casein) or unbalanced diets (high lipid, 30% lard or low protein, 6% casein) with or without 50 ppm Phenoclor DP6. The high-lipid diet supported a more rapid body weight gain but had little impact on cytochrome P-450 content, expressed either per whole liver or per mg microsomal protein, and on the incorporation of the precursor into cytochrome P-450. The latter was determined by measuring the radioactivity incorporated into the cytochrome P-450 fraction, partially purified by afffinity chromatography, as well as into two cytochrome P-450 isozymes ( M r 50 000 or 52 000) purified by DEAE-52 cellulose ion-exchange chromatography. The low-protein diet, on the other hand, severely depressed body weight gain and cytochrome P-450 content as well as incorporation of radioactivity, the lower- M r cytochrome ( M r 50 000) being particularly affected. However, when a potent inducer, Phenoclor DP6, was added to the low-protein diet, cytochrome synthesis was restored indicating that the effect was reversible.

Methodological studies of the metabolism-oriented determination of the lysine requirement in broiler chickens. 1. Influence of the lysine content of the diet on the lysine oxidation rate in short-term food withdrawal before 14C-lysine injection

For the estimation of lysine requirement 128 male broiler chickens were used at an age of 7 to 21 days posthatching. They received a lysine deficient diet composed of wheat and wheat gluten. To this basal diet L-lysine-HCL was supplemented successively resulting in 8 lysine levels ranging from 5.8 to 23.3 g lysine per kg DM (2.2 to 8.7 g lysine per 16 g N). At the end of the two-week feeding period of the experimental diets 14C-lysine was injected intravenously 1.5 and 5.5 hours after feed withdrawal. During the following 4 hours the excretion of CO2 and 14CO2 was measured. This 4 hours absorption period for 14CO2 was regarded as sufficient according to a preliminary experiment. The highest daily gain of 21.5 g was observed in animals fed 13.3 g lysine/kg DM. Lysine concentrations exceeding 18.3 g/kg DM depressed body weight gain. The CO2-excretion was not influenced by lysine intake. The 14CO2-excretion was low with diets low in lysine content and increased 3 to 4 times with diets meeting the lysine requirement. Based on measurements 1.5 to 5.5 hours after feed withdrawal the saturation value for lysine was reached at 13.3 g/kg DM. This value was lowered (10.8 g/kg DM), however, if the estimation was carried out 5.5 to 9.5 hours after feed withdrawal. These results suggest a higher metabolic lysine requirement during the earlier period after feed intake. Both, reduced weight gain and non linearity in 14CO2-excretion with diets exceeding a lysine content of 18.3 g/kg DM indicate a limited capacity of the organism to degrade excessive lysine. According to the results of this experiment for broiler chickens 3 weeks posthatching a lysine requirement between 10.8 and 13.3 g/kg DM (27% CP and 660 EFUhen/kg DM) was concluded. The range of estimated requirement data could be narrowed by the use of diet with other lysine content.

Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil.

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).

Electrophysiological investigation of 2,5-hexanedione neurotoxicity in rats

Rats were subcutaneously administered 0.8 ml/kg/day 2,5-hexanedione for periods of 18, 25, and 32 days, respectively, and were processed for electrophysiological observations. Action potential and membrane currents were recorded from the sciatic nerve under current- and voltage-clamp conditions. The contractile responses of gastrocnemius and diaphragm muscles following sciatic nerve and phrenic nerve stimulation, respectively, were observed. Animals developing peripheral neuropahy showed hindlimb weakness and depression of body weight gain. Current- and voltage-clamp experiments have shown that after 32 days treatment, the amplitude of the action potential recorded from single myelinated nerve fibers was reduced and the duration was slightly increased; peak sodium current was reduced by 15% and high potassium current density (12 nA) appeared. The twitch responses of diaphragm and gastrocnemius muscles following electrical stimulation of the phrenic and sciatic nerves, respectively, were strongly affected in the 32 day-treated rats. The results are discussed in terms of demyelination which should increase the amplitude of delayed current by exposing potassium channels which under physiological conditions are buried under the myelin sheath.

Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

The effects of DEHP on sperm morphology and on peripheral blood micronuclei were studied for 12 weeks following five subacute IP injections of DEHP at 1/6, 1/12, and 1/60 of the LD50 per day. Sperm morphology was examined in both adult mice and rats, while peripheral blood micronuclei were scored in mice up to 4 weeks after treatment. In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks. Numbers of morphologically abnormal sperm did not differ from controls in the 12 weeks following treatment. In addition, DEHP did not increase the numbers of peripheral blood micronuclei. Studies in the rat indicated that exposure to doses of 1/6 and 1/12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls. Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment. In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells. Although DEHP is known to cause testicular atrophy in rats and to a lesser extent in mice, it did not cause an increase in abnormal sperm in either species. Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line.

Dietary Protein and Yolk Sac Inoculation with Escherichia coli in Young Turkeys

An experiment was conducted to examine the effect of pathogenic Escherichia coli inoculated into the yolk sac of day-old turkeys. Escherichia coli was isolated from the yolk sac of stunted poults and inoculated directly into the yolk sac of day-old birds. Poults were administered either .1 ml of uninoculated sterile Todd-Hewitt broth or .1 ml of a 10−3 or 10−2 dilution of a 24-hr E. coli culture containing 3.4 × 108 viable bacteria/ml. In addition, poults were fed either 28 or 22% protein diets from 0 to 21 days of age to form a 3 × 2 factorial arrangement. Body weight gain and feed consumption were measured weekly, and dry matter and protein retention and nitrogen-corrected metabolizable energy were measured from 7 to 10 and 17 to 20 days postinoculation. Intestinal mucosal dipeptidase and maltase activities were determined at 21 days of age.Average mortality by 7 days of age was increased from 1 to 36% from the E. coli inoculation of the yolk sac. Escherichia coli significantly depressed body weight gain and feed consumption 27 and 30, 13 and 16, and 6 and 8%, respectively, during the first, second, and third weeks of the experiment but failed to affect feed efficiency. Feeding a 28% protein diet alleviated the depression in feed consumption and body weight gain to some extent compared with a substantial depression at 22% protein.Nitrogen content and gross energy of the excreta were increased by both dilutions of E. coli for the 7 to 10-day period; this was indicative of a malabsorption of nutrients. Dry matter and nitrogen retention values were variable in the 7 to 10-day period and did not differ during the 17 to 20-day period. Changes in mucosal maltase and dipeptidase activities varied along the length of the intestine at 21 days of age.

Reproduction in Fischer-344 rats exposed to methyl chloride by inhalation for two generation

Male and female Fischer-344 rats were exposed to methyl chloride by inhalation (0, 150, 475, or 1500 ppm, 6 hr/day, 5 days/week, 40 males and 80 females per group). The only treatment-related clinical signs were a 10 to 20% body weight gain depression (BWGD) in both males and females exposed to 1500 ppm at all weekly weighings after 2 weeks of exposure and a 5–7% BWGD in 475-ppm exposed animlas after Day 57. After 10 weeks the exposure schedule was changed to 6 hr/day, 7 days/week and each male was mated to two exposed females. The mating period was ended after 2 weeks, at which point 10 males/group were necropsied. The only tratment-related lesions found were severe bilateral testicular degeneration ( 10 10 ) and granulomas in the epididymis ( 3 10 ) in the 1500-ppm males. The remaining 30 males per group were then removed from exposure and mated during a 2-week period with 60 unexposed females. The exposed females were continued on exposure from the start of mating to Postnatal Day 28 (6 hr/day, 7 days/week). The females were not exposed from Gestation Day 18 to Postnatal Day 4, and the pups were never directly exposed prior to weaning. There were no significant differences between groups in the number of exposed or unexposed females that mated, as evidenced by copulation plugs. No litters were born to exposed or unexposed females mated to the 1500-ppm males. There was no significant difference in the number of litters produced by the 150-ppm groups when compared to the control groups. Fewer litters were born in the 475-ppm groups than in the control groups. No differences in litter size, sex ratio, pup viability, or pup growth were found among the 475-ppm, 150-ppm, or control F 0 groups. When bred 10 weeks after the cessation of exposures, 5 to 20 1500-ppm F 0 males had regained the ability to sire normal litters. The same number of 475-ppm F 0 males proved as fertile ( 15 20 ) as control F 0 males ( 13 20 ). After weaning, F 1 pups from the 475-, 150-, and 0-ppm groups were exposed to the same concentrations of methyl chloride for 10 weeks and then mated. A trend toward decreased fertility was found in the 475-ppm F 1 group.