Induction of rat hepatic microsomal enzymes by toxaphene pretreatment

Abstract

The effects of pretreatment of rats with toxaphene on hepatic drug metabolizing enzymes and several other parameters of the mixed function oxidase system were investigated. Adult male Sprague‐Dawley rats were fed diets containing 0, 50, 100, 150 and 200 ppm of toxaphene for 14 days. The body weight gain was unaltered as well as the food consumption in all the toxaphene fed groups. There was no change in the weights of brain, kidney, heart, and testes but the liver weight was significantly increased. The thymus weight in all the toxaphene fed groups was decreased. Hydroxylation of pentobarbital and aniline was significantly enhanced in rats exposed to toxaphene. Ethylmorphine‐N‐demethy‐lase activity in the toxaphene treated rats was also elevated. Enhanced hydroxylation of pentobarbital was also evident from the decreased sleeping time following pentobarbital administration. Exposure to toxaphene increased cytochrome P‐450, NADPH‐cytochrome c‐reductase and dehydrogenase in hepatic microsomal fractions. The binding of aniline and hexobarbital to microsomes was also enhanced, suggesting that the intermediate steps in the electron‐transfer system were increased. In conclusion, pretreatment of rats with toxaphene for fourteen days resulted in the induction of the hepatic mixed function oxidase system.     

The subchronic toxicity of acridine in the rat

Abstract

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O‐deethylase (EROD) and pentoxyresorufin O‐dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose‐related increases in inorganic phosphate and uric acid levels. Treatment‐related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose‐dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.     

Pentachlorotoluene and pentabromotoluene: results of a subacute and a subchronic toxicity study in the rat

Pentachlorotoluene (PCT) and pentabromotoluene (PBT) are environmental contaminants detected in the Great Lakes ecosystem. In view of the paucity of toxicity data and the potential for human exposure, a subacute (28 day) and a subchronic (91 day) study were conducted in the rat. In the subacute study, groups of 10 male and 10 female rats were fed the diet containing PCT or PBT at 0, 0.5, 5.0, 50 or 500 ppm for 28-days. In the subchronic study, the group size was increased to 15, the dose levels were 0, 0.05, 0.5, 5.0, 50 and 500 ppm in the diet and the exposure period was 91 days. Growth rate and food consumption were not affected by exposure to either chemical in the subacute and subchronic study. Clinical observations revealed no abnormalities. Decreased hemoglobin was observed in female rats fed 5.0 ppm PCT and higher levels in the subacute (28 day) study. In the same study the hematocrit value and erythrocyte numbers of females fed 5.0 or 500 ppm PCT diets were significantly lower than the control. In both subacute and subchronic studies mild dose-dependent histopathological changes were observed in the thyroid, liver and kidney of rats fed PCT and PBT diets. In general male rats were more susceptible than females to the treatment of PCT and PBT. Based on these data, it was concluded that the no observable adverse effect level for PCT was 50 ppm in the diet (3.5 mg/kg b.w./day) and that of PBT was 5.0 ppm (0.35 mg/kg b.w./day).     

Toxicity of trichlorotoluene isomers: a 28-day feeding study in the rat

Groups of 10 male and 10 female rats were fed alpha,alpha,alpha-, alpha,2,6- or 2,3,6- trichlorotoluene (TCT) in their diet at 0, 0.5, 5.0, 50 or 500 ppm for 28 days. Growth rate and food consumption were not affected by treatment. No deaths occurred. Significant increases in liver weights were observed in male rats fed 5.0 and 500 ppm 2,3,6-TCT. Mild serum biochemical changes occurred in male rats. These included increased SDH activities in the groups fed 5.0 and 50 ppm alpha, alpha, alpha-TCT, and 5.0 ppm 2,3,6-TCT. Alpha, alpha, alpha-TCT at 500 ppm caused elevated LDH activities in male rats. Hepatic microsomal aminopyrine N-demethylase activities were increased in male rats fed 500 ppm alpha,2,6-TCT. Hematological parameters were not affected by treatment. Mild histological changes were seen in the liver, kidney and thyroid of treated rats. Data presented here suggest that alpha, alpha, alpha-, alpha,2,6- and 2,3,6-TCT possess a low order of oral toxicity in the rat.     

Pentachlorotoluene and pentabromotoluene: Results of a subacute and a subchronic toxicity study in the rat

Abstract

Pentachlorotoluene (PCT) and pentabromotoiuene (PBT) are environmental contaminants detected in the Great Lakes ecosystem. In view of the paucity of toxicity data and the potential for human exposure, a subacute (28 day) and a subchronic (91 day) study were conducted in the rat. In the subacute study, groups of 10 male and 10 female rats were fed the diet containing PCT or PBT at 0, 0.5, 5.0, 50 or 500 ppm for 28‐days. In the subchronic study, the group size was increased to 15, the dose levels were 0, 0.05, 0.5, 5.0, 50 and 500 ppm in the diet and the exposure period was 91 days. Growth rate and food consumption were not affected by exposure to either chemical in the subacute and subchronic study. Clinical observations revealed no abnormalities. Decreased hemoglobin was observed in female rats fed 5.0 ppm PCT and higher levels in the subacute (28 day) study. In the same study the hematocrit value and erythrocyte numbers of females fed 5.0 or 500 ppm PCT diets were significantly lower than the control. In both subacute and subchronic studies mild dose‐dependent histopathological changes were observed in the thyroid, liver and kidney of rats fed PCT and PBT diets. In general male rats were more susceptible than females to the treatment of PCT and PBT. Based on these data, it was concluded that the no observable adverse effect level for PCT was 50 ppm in the diet (3.5 mg/kg b.w./day) and that of PBT was 5.0 ppm (0.35 mg/kg b.w./day).     

Toxicity of pirimiphos-methyl: I. The acute and subacute oral toxicity in albino rats

In an acute study, albino rats of both sexes were orally administered graded doses of Pirimiphosmethyl, and the statistically computed median lethal dose (LD-50) were 1861 and 1667 mg/kg body weight for male and female rats respectively. No treatment related changes were discernible with regard to food intake, growth, gross or histopathology of the organs. In a time-course study, the correlation between symptoms and degree of esterase inhibition was examined in rats administered the minimum lethal dose (MLD: 1000 mg/kg b.w.) of the insecticide. Time-course inhibition pattern of both cholinesterase (ChE) and non-specific carboxylesterase (NSE) activities in brain and plasma revealed maximum inhibition at 24 h post-treatment which correlated well with the intensity of symptoms. In a subacute study, groups of male rats were fed dietary Pirimiphos-methyl at 0, 10, 250, 500 and 1000 ppm for 28 days. Food consumption and growth rate were not affected throughout the experimental period. At necropsy after 28 days, no gross pathological changes were seen in any of the organs except a slight increase in liver weight at 1000 ppm. Though no statistical differences were observed in the levels of hepatic transaminases, a significant increase in serum transaminase was evident. Significant increase in the activities of hepatic ALP, beta-GLR and serum ALP were evident at 500 and 1000 ppm. Further, significant inhibition of plasma PChE was evident at 250, 500 and 1000 ppm while the degree of inhibition of brain AChE was significant only at the higher dosages. No histopathological alterations were observed in any of the organs.     

Effect of cadmium on ATPase activities in rats fed on iron-deficient and sufficient diets

Male Sprague-Dawley rats were fed on different levels of cadmium mixed with purified diets containing iron or no iron for 8 weeks. The body weight gain, tissue weights, hemoglobin, hematocrit, liver and brain ATPase were measured at 2, 4 and 8 weeks after feeding. The hemoglobin and hematocrit values were the same in all rats fed on cadmium. The rats fed on iron-deficient diets mixed with cadmium showed a significant decrease in body weight gain. However, the rats receiving only the 100 ppm of cadmium in iron-sufficient diet showed a significant decrease in body weight gain. There were no significant changes in the weights of thymus, spleen, kidney, heart, brain and testes. However, the liver weights were decreased in the highest treatment of cadmium but the liver weight/body ratios were uneffected. Na+-K+ activated ATPase activity in brains of rats fed on cadmium were significantly decreased at 2, 4 and 8 weeks of treatment. The decrease was more pronounced in rats fed on iron-deficient diets. Oligomycin-sensitive (Mitochondrial) Mg2+ ATPase activity was also significantly decreased in liver and brain tissues of rats fed on cadmium. Oligomycin-insensitive Mg2+ ATPase activity, however, was not altered in any tissues tested. It appears that cadmium may be interfering with energy (ATP) production and utilization processes in rat brain and liver tissues.     

Toxicological assessment of chlorinated diphenyl ethers in the rat, Part II

Chlorinated diphenyl ethers (CDE's) are environmental contaminants that have been found in Great Lakes fish. Because of the paucity of toxicity data and potential for human exposure, the present short-term study was conducted to assess their potential toxic effects. Groups of 10 male and 10 female rats were administered the three CDE congeners (2,2',4,4',5-pentachlorodiphenyl ether (PCDE), 2,2',4,4',5,5'-hexachlorodiphenyl ether (HCDE), 2,2',3,4,4',6,6'-heptachlorodiphenyl ether (HPCDE] in diets at levels of 0.5, 5.0, 50 or 500 ppm for a period of 4 weeks. Decreased food consumption was observed with male and female rats fed the diet containing 500 ppm HPCDE. Treatment with the three isomers at the highest dose level produced an increase in liver weight in both sexes. While administration of PCDE produced an increase in hepatic aminopyrine demethylase activity, HCDE caused a significant increase in aminopyrine demethylase, aniline hydroxylase and ethoxyresorufin de-ethylase activities. HPCDE caused a significant increase in ethoxyresorufin de-ethylase activity. HPCDE at the highest dose level also caused a significant reduction in circulating lymphocytes in male rats. The 3 CDE's produced mild and adaptative histological changes in the liver and thyroid, but only HPCDE elicited mild changes in the thymus, bone marrow, and spleen. The above data indicate that HPCDE is immunosuppressive and that all three CDE isomers are considered to be moderately toxic in rats. The no-observable effects levels appear to be between 5-50 ppm in diet (0.36-3.0 mg/kg b.w.) for the three CDE's.     

Anaerobic microbial dechlorination: an approach to on-site treatment of toxaphene-contaminated soil

Enhanced microbial degradation of toxaphene by natural microorganisms occurred in soil and sediment amended with organic matter kept under anaerobic (flooded) conditions. Laboratory experiments yielded a dissipation half-life of approximately 3 and 1 week for soil and sediment, respectively, containing 10 ppm of technical toxaphene and a 1% alfalfa meal amendment. Dissipation was accompanied by an increase in early eluting gas chromatographic peaks and a decrease in later eluting peaks, indicating that dechlorination had occurred. Enhanced anaerobic dissipation also took place in soil containing 500 ppm of toxaphene, although at a lesser rate than at 10 ppm, and when cotton gin waste was used as amendment in place of alfalfa meal. Sediment in a toxaphene-contaminated pesticide waste disposal ditch was amended with 10% steer manure and flooded to ascertain field utility of the technique for on-site decontamination. Toxaphene residues were reduced from 63 to 23 ppm in 120 days, and some degradation activity still occurred up to 8 months after this single treatment.     

Effect of maternal dietary hexachlorocyclohexane exposure on pup survival and growth in albino rats.

In adult albino rats, maternal dietary beta- and gamma-hexachlorocyclohexane (HCH) intake during gestation upto 400 ppm level did not affect the number of litters produced. But about 50 and 100% pup mortality was found in 200 and 400 ppm beta-HCH group within 5 days of birth. Maternal mortality was observed in 800 ppm beta-HCH group during third week of gestation. The effect of maternal dietary intake of HCH isomers at 50 and 250 ppm level during gestation and/or lactation on perinatal development was also studied. The body weights and sizes of the newborn litters of mother rats exposed to dietary HCH isomers did not differ from controls. Similarly, the growth and development of the litters of HCH exposed mother rats that survived 28 day lactation period were found to be comparable to controls as evidenced by the body weight and weight of vital organs. However, liver weight increases were found in the 28 days weaned litters wherever the mothers had been exposed to HCH isomers during lactation. Lowered kidney weight was seen in litters of mother rats fed 250 ppm gamma-HCH during gestation and lactation. The brain and testis weights were not affected in the litters of any experimental groups.     

Metabolism of gamma‐hexachlorocyclohexah (HCH) in vivo. Metabolism of orally administered gamma‐2,3,4,5,6‐pentachlorocyclohexen (PCCH)

Abstract

Mexacarbate (4‐dimethylamino‐3,5‐xylyl N‐methylcarbamate) insecticide has potential for use in spruce budworm (Choristoneura fumiferana Clem.) control operations in Canada. Its persistence and fate in balsam fir (Abies balsamea (L.) Mill.), litter and soil samples were studied by spraying aerially oil‐based and water‐based formulations, each at 70 g A.I./ha over a coniferous forest near Bathurst, New Brunswick. The oil‐based formulation gave the maximum concentration of the chemical in the substrates studied. In fir needles, the highest concentrations observed were 0.51 ppm and 0.19 ppm (fresh weight) for the oil‐based and emulsion formulations respectively, 1 h after application. The residue levels decreased very rapidly with a half‐life of approximately 5 h. Three and eight days after the spray application of the emulsion and oil formulations respectively, the concentrations of mexacarbate in foliage decreased to trace levels ( 0.008 ppm). Only very low levels of residue were detected in litter and soil. The peak concentrations for the two formulations ranged from 0.02 to 0.11 ppm (fresh weight) in litter and from 0.01 to 0.06 ppm (fresh weight) in soil. The residue levels in both litter and soil decreased to below the detection limit (0.005 ppm) within 1 d. The ground deposit levels found on glass plates and the droplet density and size spectra measured on Kromekote® cards reflected the variations in concentrations found in fir needles, litter and soil samples and correlated with the observed maximum concentrations in them. Under the stipulated use pattern, mexacarbate concentrations found in the terrestrial components studied were low and are not likely to have any undue adverse effects on non‐target species.     

Mixture effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyl congeners in rats

Concern of the toxic effects and bioaccumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls in the environment continues to be a focus of research in persistent organochlorine contaminants. Groups of five adult female S.D. rats were administered by gavage 0, 2.5, 25, 250 or 1000 ng TCDD/kg body weight/day or TCDD in combination with a mixture of PCB congeners (PCBs) at 2 or 20 microg/kg b.w./day for a period of 28 days. Growth suppression, increased absolute and relative liver weights, and decreased thymic weight were observed in either the 1000 ng TCDD group alone, or the groups receiving a mixture of 1000 ng TCDD + 2 microg PCBs. The TCDD induced increases in liver and thymic weights were not altered by co-administration with PCBs, however, growth suppression appeared to be more pronounced in the group receiving 1000 ng TCDD + 2 microg PCBs than with TCDD alone. Treatment with TCDD at 250 ng and 1000 ng/kg resulted in a significant increase in hepatic microsomal methoxy resorufin-O-demethylase and ethoxy resorufin-O-deethylase activities which were antagonized by co-administration with PCBs. Similarly, effects of 250 ng TCDD on serum cholesterol and liver UDP glucuronosyl transferase activity and ascorbic acid were significantly reduced by co-administration with 20 microg PCBs. Other biochemical effects elicited by treatment with 1000 ng TCDD, but not affected by co-administration with PCBs include the following: increased serum albumin, decreased liver vitamin A, and increased kidney vitamin A and liver microsomal glutathione-S-transferase activity. While decreased hemoglobin, platelet, packed cell volume and red cell indices were observed in TCDD treated rats, no interactive effects were seen. The above results indicate that the mixture effects of PCBs and TCDD may be additive or antagonistic depending on the dose level and endpoints measured. For the purpose of predicting mixture effects, knowledge of mechanisms of action and toxicokinetics is required.     

Effect of maternal dietary hexachlorocyclohexane exposure on pup survival and growth in albino rats

Abstract

In adult albino rats, maternal dietary. ß‐ and ?‐hexachlorocyclohexane (HCH) intake during gestation upto 400 ppm level did not affect the number of litters produced. But about 50 and 100% pup mortality was found in 200 and 400 ppm ß ‐HCH group within 5 days of birth. Maternal mortality was observed in 800 ppm ß ‐HCH group during third week of gestation. The effect of maternal dietary intake of HCH isomers at 50 and 250 ppm level during gestation and/or lactation on perinatal development was also studied. The body weights and sizes of the newborn litters of mother rats exposed to dietary HCH isomers did not. differ from controls. Similarly, the growth and development of the litters of HCH exposed mother rats that survived 28 day lactation period were found to be comparable to controls as evidenced by the body weight and weight of vital organs. However, liver weight increases were found in the 28 day weaned litters wherever the mothers had been exposed to HCH isomers during lactation. Lowered kidney weight was seen in litters of mother rats fed 250 ppm ?‐HCH during gestation and lactation. The brain and testis weights were not affected in the litters of any experimental groups.     

Adenosine triphosphatase activities in brain, kidney and liver of mice treated with toxaphene.

The sensitivity of Na+-K+ and Mg++ Adenosine Triphosphatases (ATPases) in mouse tissues to toxaphene, a highly chlorinated camphene, was determined both in vivo and in vitro. The brain and kidney Na+-K+ ATPase activities were significantly inhibited in vitro by toxaphene. Interestingly, the inhibition was not significantly increased with an increase in the concentration of toxaphene. The oligomycin-sensitive (mitochondrial Mg++ ATPase activities in mouse brain, kidney and liver fractions were significantly inhibited by toxaphene in a concentration-dependent fashion. The oligomycin-insensitive Mg++ ATPase in all tissues examined was also inhibited but less sensitive to toxaphene than mitochondrial Mg++ ATPase. In contrast to in vitro response, the brain ATPases were not altered in mice fed toxaphene by oral intubation for three days. The renal and hepatic ATPase activities were significantly decreased in toxaphene treated mice with the oligomycin-insensitive Mg++ ATPase activity being only slightly altered.     

Lack of effects of atrazine on estrogen-responsive organs and circulating hormone concentrations in sexually immature female Japanese quail (Coturnix coturnix japonica)

The widely used herbicide, atrazine, has been reported to exhibit reproductive toxicity in rats and amphibians. The present studies investigate toxicity of atrazine in Japanese quail and its ability to influence reproduction in sexually immature females. Atrazine was administered in the diet at concentrations from 0.001 to 1000 ppm (approximately 109 mg kg-1 per day) or systemically via daily subcutaneous injections (1 and 10 mg kg-1) or Silastic implants. Atrazine did not cause overt toxicity in sexually immature female quail (no effects on change in body weight, feed intake, mortality or on circulating concentrations of the stress hormone, corticosterone). It was hypothesized that if atrazine were to have estrogenic activity or to enhance endogenous estrogen production, there would be marked increases in the weights of estrogen sensitive tissues including the oviduct, the liver and the ovary together with changes in gonadotropin secretion. However, atrazine had no effect on either liver or ovary weights. Atrazine in the diet increased oviduct weights at 0.1 and 1 ppm in some studies. These effects were not consistently observed and were not significant when data from studies were combined. Systemic administration of atrazine had no effect on oviduct weights. Dietary (concentrations from 0.001 to 1000 ppm) and systemically administered atrazine had no effect on circulating concentrations of luteinizing hormone (LH). The present studies provide evidence for a lack of general or reproductive toxicity of atrazine in birds.     

Long-term toxicology and carcinogenicity of 2,4,6-trichlorophenol

Carcinogenesis bioassays were conducted by giving 2,4,6-trichlorophenol [2,4,6-TCP] in feed to groups of 50 male and female Fischer rats and male B6C3F1 mice for two years. Dietary concentrations were 0 [20/group], 5000 [0.5%], or 10,000 [1%] ppm. Female mice began with 10,000 and 20,000 ppm but after 38 weeks were lowered due to reduced body weights to 2500 and 5000 ppm for 67 weeks; exposures averaged 5200 and 10,400 ppm. Adverse effects at two years were leukocytosis and monocytosis of peripheral blood and hyperplasia of bone marrow in both sexes of rats. In mice, liver toxicity, including individual liver cell abnormalities, focal areas of cellular alteration, and focal and nodular areas of hyperplasia were commonly present. Regarding carcinogenic activity, TCP caused leukemias/lymphomas in male rats, and possibly in female rats and female mice as well, and induced liver tumors in male and female mice. Using NTP categories of evidence indicates ‘clear evidence of carcinogenicity’ for male rats [hematopoietic system tumors]; ‘equivocal evidence of carcinogenicity’ for female rats [hematopoietic system tumors]; ‘clear evidence of carcinogenicity’ for male and female mice [liver tumors].     

A two-generational reproductive toxicity study of zinc in rats

A two-generation reproductive toxicity study of zinc chloride (ZnCl(2)) was conducted in rats. F(o) male and female rats were administered 0.00 (control), 7.50 (low), 15.00 (mid) and 30.00 (high) mg/kg/day of ZnCl(2). Selected F(1) male and female rats were exposed to the same doses received by their parents (F(o)). Exposure of F(0) parental rats to ZnCl(2) showed significant reduction in fertility, viability (days 0 and 4), and the body weight of F(1) pups from the high-dose group but caused no effects on litter size, weaning index, and sex ratio. Similarly, the continued exposure of F(1) parental rats to ZnCl(2) also reduced fertility, liter size, viability (day 0), and the body weight of F(2) pups within the high-dose group but caused no effects on weaning index and sex ratio. Exposure of ZnCl(2) to F(0) and F(1) parental males resulted in a significant reduction in their body weights, and the F(0) and F(1) parental females did not show any significant difference in their body weights compared to their control groups. However, the postpartum dam weights of both F(0) and F(1) female rats were significantly reduced compared to their controls. Exposure of ZnCl(2) to F(o) and F(1) generation parental rats did not produce any significant change of their clinical signs as well as their clinical pathology parameters, except the alkaline phosphotase (ALK) level, which showed an upward trend in both sexes of both generations. Exposure of ZnCl(2) to F(0) rats resulted in a reduction of brain, liver, kidney, spleen and seminal vesicles weights of males and in the spleen and uterus of females. Similarly, exposure of F(1) rats to ZnCl(2) also resulted in reduction of brain, liver, kidney, adrenal, spleen, prostate and seminal vesicles weights of males and in spleen and uterus of females. ZnCl(2) exposure resulted in grossly observed gastro-intestianla (GI) tract, lymphoreticular/hematopoietic, and reproductive tract lesions in parental rats in both generations. Reduced body fat was also recorded in F(1) parental rats.     

Reproductive success of barn swallows nesting near a selenium-contaminated lake in east Texas, USA

Reproductive success and contaminant levels in 1986 and 1987 were compared between Barn Swallows nesting at selenium-contaminated Martin Lake, Texas, USA, and swallows nesting at a reference site. Nests were initiated about the same time or earlier at Martin Lake than at the reference site and clutch size was similar between the two locations. Nest success was significantly higher at Martin Lake than at the reference site and no embryo or chick deformities were documented. Selenium concentrations in 14 of 20 eggs from Martin Lake were above background (> 3 ppm, dry weight); two of 20 eggs contained > 5 ppm, a concentration associated with a 20% embryo mortality/deformity rate in some bird species. Selenium concentrations in the kidneys of adult swallows were higher at Martin Lake (mean = 14 ppm dry weight) than at the reference site (5.8 ppm). DDE, the only detected organochlorine compound, was in two of 10 eggs from Martin Lake; these concentrations were below those associated with chronic poisoning and reproductive problems. The maximum mercury concentration in livers of adult Barn Swallows (0.83 ppm, dry weight) was within the range for background levels (< 5 ppm).     

Effects of dietary zinc supplementation on hen performance, ammonia volatilization, and nitrogen retention in manure

This investigation was undertaken to evaluate the effects of dietary ZnSO4 supplementation on ammonia volatilization and nitrogen retention in hen manure. One hundred twenty, 45-wk-old commercial Leghorn laying hens were sequentially fed diets with 1000, 2000, and 3000 ppm Zn as ZnSO4 (Zn-1000, Zn-2000, and Zn-3000), then followed by two control dietary periods with 114 ppm Zn (Control-1 and Control-2) for a total of five consecutive eight-day experiment periods, respectively. When hens were fed the 1000 and 2000 ppm Zn treatment diets, room ammonia levels were significantly reduced compared to the control diets. Dietary Zn treatments reduced the decomposition of uric acid, resulting in an increase in manure total-N retention compared to the control fed birds. The 1000 ppm Zn supplement had no adverse effects on hen body weight, feed consumption, egg production, egg weight, albumen height, or shell thickness. However, hens fed the diet containing 3000 ppm Zn had significantly depressed body weight, feed consumption, egg production, egg weight, and shell thickness. Zinc levels of egg contents increased linearly as dietary Zn levels increased. These levels in eggs would not be a problem for human consumption because these are much less than the daily Zn recommended dietary allowance. Although land application of such manure will not cause environmental problems or crop toxicity, proper monitoring of soil and crop Zn levels and effective nutrient management planning would be well advised.     

Developmental exposure to diuron causes splenotoxicity in male Sprague-Dawley rat pups

This study investigated whether perinatal exposure to diuron [3-(3,4-dichlorophenyl)-1-1-dimethylurea] might exert adverse effects on rat lymphoid organs. Pregnant Sprague-Dawley (SD) rats were exposed to diuron at 500, 750 or 1250 ppm in the diet from gestational days (GD) 12-21 and during lactation. At postnatal day (PND) 42, male pups were euthanized and thymus, spleen, mesenteric lymph node and femur were collected for histopathological analysis. Food consumption and body weight gain were significantly reduced in dams exposed to 1250 ppm during gestation period. Also, Diuron at 750 and 1250 ppm produced: (1) increased relative spleen weight associated histologically with severe congestion in red pulp, (2) enhanced extramedullary hematopoiesis and hemosiderosis as well as (3) depletion of lymphoid follicles in white pulp. Flow cytometric analysis revealed a significant reduction in B lymphocytes (CD45RA+) in male pups but T lymphocytes (CD4+, CD8+ and CD4+/CD8+) were not markedly affected. Thus, data suggest that Diuron-induced maternal toxicity in dams exposed to high dose and perinatal exposure to this herbicide produced spleen toxicity as evidenced by a reduction in B lymphocyte number in male SD pups.