Brain myelination in rats treated with ionizing radiation in utero

Abstract

Effects of ionizing radiation on brain myelination and some physical development parameters were studied in laboratory rats (Fisher F‐344 inbred strain). Rats were treated with three different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Exposure to 150 rad reduced body, brain, ovary, kidney, heart and spleen weights. Prenatal exposure to 150 rad of radiation reduced the cerebral cortex weight by 22 percent at 30 days of age, and 20 percent at 52 days of age which caused a reduction in cerebral cortex myelin content by 20 and 23 percent at the ages of 30 and 52 days respectively. This dose did not affect the myelin content of the cerebellum or the brain stem, or the myelin concentration (mg myelin/g brain tissue) of the cerebral cortex, cerebellum, and the brain stem. The cerebral cortex weight of the 15 rad treated rats was reduced at the age of 30 days. Exposure to 15 rad, and 6.8 rad did not affect either the myelin content or the myelin concentration of these brain areas.     

Brain myelination in rats treated with ionizing radiation in utero.

Effects of ionizing radiation on brain myelination and some physical development parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with three different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Exposure to 150 rad reduced body, brain, ovary, kidney, heart and spleen weights. Prenatal exposure to 150 rad of radiation reduced the cerebral cortex weight by 22 percent at 30 days of age, and 20 percent at 52 days of age which caused a reduction in cerebral cortex myelin content by 20 and 23 percent at the ages of 30 and 52 days respectively. This dose did not affect the myelin content of the cerebellum or the brain stem, or the myelin concentration (mg myelin/g brain tissue) of the cerebral cortex, cerebellum, and the brain stem. The cerebral cortex weight of the 15 rad treated rats was reduced at the age of 30 days. Exposure to 15 rad, and 6.8 rad did not affect either the myelin content or the myelin concentration of these brain areas.     

Effects of long-term chlorpyrifos exposure on mortality and reproductive tissues of Banded Gourami (Trichogaster fasciata)

Abstract

This study assessed the long-term toxicity of chlorpyrifos on survival and reproduction of Banded Gourami by using mortality, gonado-somatic index (GSI) and histopathological observations as endpoints. Adult fish were exposed to five different concentrations of chlorpyrifos (0, 15, 50, 150, 500?µg/L) in 15 PVC tanks for 15, 30, 45, 60 and 75?days. Results showed that all male and female fish died after 15?days of 500?µg/L chlorpyrifos exposure. No consistent significant effect was observed for both male and female GSI. Furthermore, results showed dose- and time-dependent histopathological alterations for both ovary and testes. The 60-d No Observed Effect Concentration (NOEC) for most histopathological alterations of Banded Gourami ovary and testes was 50?μg/L, while 60-d NOEC for mortality of both male and female fish was < 15?μg/L. The results show that the long-term exposure to chlorpyrifos not only affect the reproductive tissues of Banded Gourami at exposure concentrations but also cause their mortality. Future studies should evaluate effects at lower concentrations.     

Prenatal and postnatal exposure to diazinon and its effect on spermatogram and pituitary gonadal hormones in male offspring of rats at puberty and adulthood

The objective of this research is to study the possible reproductive adverse effects of diazinon on rat offspring exposed in utero and during lactation. Twenty-four Sprague–Dawley female rats (10–12 week old) were randomly assigned to four groups, each consisting of six rats. Group 1 served as the control and these rats were given normal saline orally. Rats in groups 2, 3, and 4 were administered diazinon, dissolved in saline at 10, 15, 30 mg/ kg^?1 body weight, per oral, once daily, during mating, pregnancy and lactation. The male offsprings were examined at puberty and adulthood for body weight, testis weight, epididymis weight, sperm count, motility and morphology, pituitary-gonadal hormone levels. At 30 mg kg^?1 dose, the male offsprings showed a decrease in testicular weight, sperm count, motility, with an increase in abnormal sperm percentage and a decline in pituitary-gonadal hormones, at puberty. Upon attaining adulthood, there was a decrease in testicular weight, sperm count and motility with an increase in abnormal sperm percentage and a decrease in pituitary hormone level. There was evidence of some adverse reproductive effects on the male offspring at the 15 mg/ kg^?1 dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in the offsprings, although a few parameters reverted to the normal growth pattern. Diazinon is a reproductive toxicant for male offsprings if exposed during prenatal and postnatal phases.     

Effects of chlorpyrifos on reproductive performances of guppy (Poecilia reticulata)

Guppy (Poecilia reticulata) was selected to investigate the effects of chlorpyrifos on reproductive performances. Male and female guppy with proven fertility were selected from our own colony and the groups of fish (n=72/group) were exposed to pre-determined chlorpyrifos concentrations (0.002 microg/l, 2 microg/l) based on the 96-h LC50 for guppy. Mating behavior of males was recorded on the 2nd day of exposure. Offspring were counted and survival recorded on the 14th day. Gonopodial thrusts (8/15 min) in 0.002 microg/l and (4/15 min) in 2 microg/l were significantly different from the control group (11/15 min). Similarly, live birth reduced significantly to 8/female in 2 microg/l compared to 27/female in the control group. Survival of offspring after 14 days was reduced to 47% in the 2 microg/l group compared to 94% of survival in the control. Our findings demonstrate that low soluble concentrations of chlorpyrifos affect mating behavior, number of offspring and offspring survival of guppy.     

Developmental exposure to decabromodiphenyl ether (PBDE 209): effects on thyroid hormone and hepatic enzyme activity in male mouse offspring

Decabrominated diphenyl ether (PBDE 209) is the second most used brominated flame retardant (BFRs). Many studies have shown that some of the BFRs act as endocrine disruptors via alterations in thyroid hormone homeostasis and affect development. Little is known about the effect of prenatal exposure to PBDE 209 on the development in male offspring. Using a CD-1 mouse model, we attempt to estimate the possible effect of in utero exposure to PBDE 209 on thyroid hormone and hepatic enzymes activities in male offspring. Pregnant mice were administered different doses of PBDE 209 (10, 500, and 1500 mg/kg/day) or corn oil for controls per gavage from gestational days 0-17. In adult male offspring whose mothers had been treated with 1500 mg/kg of PBD 209, hepatic enzyme activity of S9 7-ethoxyresorufin O-deethylase (EROD) was weak but significantly increased (54%). However, no significant changes were observed in S9 4-nitrophenol uridinediphosphate-glucuronosyltransferase (UDPGT) in any of the treatment groups. Serum triiodothyronine (T3) was found to have decreased significantly (ca. 21% both 10 mg/kg and 1500 mg/kg) in offspring, but not thyroxine (T4). Histopathological examination revealed that prenatal exposure of PBDE 209 might be related with cell swelling of hepatocytes in male offspring and there were mild changes in the thyroid glands in 1500 mg/kg group. These data demonstrate that PBDE 209 is likely an endocrine disrupter in male mice following exposure during development. Further studies using environmentally relevant doses are needed for hazard identification.     

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).     

A mixture of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non-ortho polychlorinated biphenyls (PCBs) changed the lipid content of pregnant Long Evans rats

Pregnant Long Evans rats received 1.0 μg/kg of dioxin toxic equivalents (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained two polychlorinated dioxins, four polychlorinated furans and three non-ortho polychlorinated biphenyls (PCBs). Rats were sacrificed on GD 16, GD 21 and postnatal day 4 (PND 4). The lipid content of fetus, pup, placenta and maternal liver, serum and adipose tissue were determined. Treated GD 16 and GD 21 fetuses had identical lipid content to the control group, yet the lipid content of treated pups on PND 4 was 32% higher than that of the control group. On the other hand, the lipid content of placenta, liver, and serum from the treated dams was 44–50%, 24%, and 38% lower than that of the control group, respectively. Thus, a low-dose mixture of dioxin-like compounds can cause changes in lipid content. The lipid content of offspring was not affected until they were exposed via lactation.     

Combined effects of hypoxia and ammonia to Daphnia similis estimated with life-history traits

The degradation of cyanobacterial blooms often causes hypoxia and elevated concentrations of ammonia, which can aggravate the adverse effects of blooms on aquatic organisms. However, it is not clear how one stressor would work in the presence of other coexistent stressors. We studied the toxic effects of elevated ammonia under hypoxia using a common yet important cladoceran species Daphnia similis isolated from heavily eutrophicated Lake Taihu. A 3?×?2 factorial experimental design was conducted with animals exposed to three un-ionized ammonia levels under two dissolved oxygen levels. Experiments lasted for 14 days and we recorded the life-history traits such as survival, molt, maturation, and fecundity. Results showed that hypoxia significantly decreased survival time and the number of molts of D. similis, whereas ammonia had no effect on them. Elevated ammonia significantly delayed development to maturity in tested animals and decreased their body sizes at maturity. Both ammonia and hypoxia were significantly detrimental to the number of broods, the number of offspring per female, and the number of total offspring per female, and significantly synergistic interactions were detected. Our data clearly demonstrate that elevated ammonia and hypoxia derived from cyanobacterial blooms synergistically affect the cladoceran D. similis.     

Toxicological response and its reversibility in rats fed Lake Ontario or pacific coho salmon for 13 weeks

Abstract

Lake Ontario coho salmon were known to contain a mixture of chemical contaminants. A previous study demonstrated that rats fed the Lake Ontario fish‐supplemented diet for 28 days exhibited mild biochemical and histological changes. The purpose of the present study was to determine the effects due to a longer term of exposure and the reversibility of these effects. Growth rate and food consumption were not affected by feeding the animals with Lake Ontario or Pacific fish‐supplemented diets for 13 weeks. No deaths were observed. Decreased spleen weights were observed in groups of males fed 1.45%, 5.8% Lake Ontario and 2.9% Pacific diet. After a 13 week recovery the spleen weights returned to normal. Decreased serum potassium was observed in male rats fed 2.9% Lake Ontario diet, and all levels of Pacific diet for 13 weeks, and was not evident following maintenance on normal diet. Serum glucose was not affected by the 13‐week period of treatment, however; a reduction in this parameter occurred in male rats fed the two highest doses of Lake Ontario diet and all doses of Pacific diet following the 13‐week recovery period. Minor hematological changes occurred only in the male rats fed either Lake Ontario or Pacific diet following a 13 week recovery period and included reduced marrow myeloid cells and myeloid/erythroid ratio. Hepatic microsomal ethoxyresorufin deethylase activity was significantly increased in rats ingesting Lake Ontario diet. Mild histological changes occurred in the liver and thyroid of the treated males, and in the liver and kidney of the treated females. These changes were attributed to the chemical residues and/or the fish diet. Data presented here indicated that the Lake Ontario fish‐supplemented diet can cause mild biochemical, hematological and histological changes but most of these were reversible when exposure was terminated.     

A mixture of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non-ortho polychlorinated biphenyls (PCBs) changed the lipid content of pregnant Long Evans rats

Pregnant Long Evans rats received 1.0 μg/kg of dioxin toxic equivalents (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained two polychlorinated dioxins, four polychlorinated furans and three non-ortho polychlorinated biphenyls (PCBs). Rats were sacrificed on GD 16, GD 21 and postnatal day 4 (PND 4). The lipid content of fetus, pup, placenta and maternal liver, serum and adipose tissue were determined. Treated GD 16 and GD 21 fetuses had identical lipid content to the control group, yet the lipid content of treated pups on PND 4 was 32% higher than that of the control group. On the other hand, the lipid content of placenta, liver, and serum from the treated dams was 44–50%, 24%, and 38% lower than that of the control group, respectively. Thus, a low-dose mixture of dioxin-like compounds can cause changes in lipid content. The lipid content of offspring was not affected until they were exposed via lactation.     

Production of male neonates in Daphnia magna (Cladocera, Crustacea) exposed to juvenile hormones and their analogs

We exposed the water flea Daphnia magna (Cladocera, Crustacea) to either juvenile hormone I (JH I), juvenile hormone II (JH II), or the juvenile hormone-mimicking insecticides kinoprene, hydroprene, epofenonane, or fenoxycarb. By 21-day reproduction tests, we investigated the effects on the number of neonates born per female and the offspring sex ratio. All six chemicals induced D. magna to produce male neonates; the male sex ratio of the offspring increased as the chemical concentration increased. EC50 values for production of male neonates were estimated as 400 (JH I), 410 (JH II), 190 (kinoprene), 2.9 (hydroprene), 64 (epofenonane), and 0.92 (fenoxycarb) microg/l. The number of neonates produced was reduced with all chemicals at the concentrations investigated. At the EC50 for male production, five of the six chemicals reduced the reproductive rate to less than 50%; the exception was epofenonane, which caused only a slight reduction in reproductive rate. These results were similar to those obtained for five juvenoids studied previously, one of which was studied here again. There are now 10 chemical substances--all juvenile hormones or their analogs-that are known to induce D. magna to produce male neonates. This suggests that juvenile hormone is involved in initiating male production followed by sexual reproduction in D. magna, and probably in most cladocerans that exhibit cyclic parthenogenesis.     

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.     

Delayed neurotoxicity of cyanofenphos in chickens

Abstract

Delayed neurotoxic ataxia, similar to that caused by neurotoxic organophosphorous compounds, has been shown to occur in hens after oral administration of Cyanofenphos (O‐ethyl‐O‐Cyanophenyl phenyl phosphonothionate) following either single or repeated oral doses. Axonal and myelin degeneration affecting the long tracts in spinal cord, peripheral nerves and medulla was demonstrated. The distal fibers with large diameters were particularly affected. This finding is a new contribution which has not been previously recorded. It implies that a thorough study of the structure‐activity relationships of phosphonothionates regarding their delayed neurotoxic effect is warranted.     

The effects of solar UV-B radiation on embryonic mortality and development in three boreal anurans (Rana temporaria, Rana arvalis and Bufo bufo).

Many species of amphibians have experienced population and range reductions. It has been hypothesized that sensitivity to UV-B may contribute to the population declines of some amphibian species. We performed field experiments to measure the effects of solar UV-B on the hatching success of three Finnish anuran species, the common frog (Rana temporaria), moor frog (Rana arvalis) and common toad (Bufo bufo). Further, the effects of natural UV-B radiation on survival of the tadpoles of the same three species of anurans were tested. A significant percentage of R. temporaria and B. bufo embryos survived when exposed to and protected from solar UV-B and hatching success was not affected by solar radiation. Elimination of solar UV-B significantly increased the hatching success of R. arvalis, but embryonic mortality was high in both treatments. The data indicates that under natural conditions, solar UV-B radiation influences embryo survival in R. arvalis, but has no effect on R. temporaria and B. bufo. Solar UV-B radiation had no effect on R. temporaria and R. arvalis tadpoles, but elimination of UV-B significantly increased survival of B. bufo tadpoles. It seems that ambient UV-radiation levels have no effect on R. temporaria but may affect R. arvalis and B. bufo at different developmental stages.     

Toxicological assessment of chlorinated diphenyl ethers in the rat

Abstract

Chlorinated diphenyl ethers are environmental contaminants that have been found in Great Lakes fish and birds. Because of their presence in the food chain, and potential for human exposure, the present short‐term study was conducted to assess their toxicity. Groups of 10 male and 10 female rats were each given by gavage 2,2’,4,4'6‐pentachlorodiphenyl ether (CDE1), 2,2’,4,4’,5,6‐hexachlorodiphenyl ether (CDE2) or 2,2’,3,3’,4,6'‐hexachlorodiphenyl ether (CDE3) at dose levels of 0.04, 0.4, 4.0 or 40 mg/kg b.w./day for a period of 28 days. The control group received an equivalent volume of corn oil only (0.5 ml/100 g b.w.). Treatment with the three CDE congeners did not result in suppression of growth rate or food consumption. Increased liver weights were seen in the animals of both sexes fed 40 mg/kg CDE2, in males treated with 40 mg/kg CDE1, and in females with 40 mg/kg CDE3. Hepatic microsomal aminopyrine demethylase activity was significantly higher in the male rats administered 40 mg/kg CDE2, and aniline hydroxylase activity was elevated in the females following the same treatment. Serum glucose, calcium, protein and urea nitrogen of CDE1‐treated males were higher than the control. Levels of uric acid, potassium and LDH of CDE3‐treated females were also elevated. No hematological changes were observed. Histological examination revealed that the liver and thyroid were the target organs affected by CDE treatment but the morphological changes were mild even at the highest dose level. Changes in the liver consisted of nuclear vesiculation and increased cytoplasmic volume. Alterations in the thyroid were characterized by increased epithelial height and follicular collapse. Based on the data presented above, the 3 CDE congeners can only be considered moderately toxic in the rat.     

Reproductive effects and bioconcentration of 4-nonylphenol in medaka fish (Oryzias latipes)

The objective of this study was to investigate the reproductive success (fertility and fecundity) of medaka (Oryzias latipes) exposed to 4-nonylphenol (4-NP) in water and the viability of their F(1) offspring. In addition, we measured the bioconcentration of 4-NP in eggs. After a 21-d exposure to 100microg/l 4-NP, medaka showed reduced egg production and fertility. Hepatic vitellogenin levels were increased significantly in males treated with 10, 50 and 100microg/l of 4-NP. In the F(1) generations, the hatchability and time to hatching of embryos in the 100microg/l treatment group were adversely affected, and 2-7microg 4-NP/g egg was found in spawned eggs (the bioconcentration factor: 30-100). These results indicate that (1) 4-NP adversely affected the reproduction (fecundity and fertility) of adult medaka, (2) 4-NP accumulated in eggs through maternal transfer and (3) these levels of 4-NP were associated with adverse effects in the F(1) offspring.     

Teratologic assessment of maleic hydrazide and daminozide,and formulations of ethoxyquin,thiabendazole and naled in rats

Abstract

Teratogenicity studies were conducted in rats treated orally from days 6–15 of gestation with single daily doses of 400–1600 mg/kg of maleic hydrazide, 300–1000 mg/kg daminozide, 125–500 mg/kg ethoxyquin or thiabendazole, or 25–100 mg/kg naled. Dams were killed on the 22nd day of gestation, and fetuses were evaluated by routine teratologic methods. No adverse effect was related to any treatment other than an increased incidence of anomalous fetuses at the highest dose (500 mg/kg) of thiabendazole.     

Toxicity of acid-sulphate soil leachate and aluminium to the embryos and larvae of Australian bass (Macquaria novemaculeata) in estuarine water

The toxicity of leachate water from acid-sulphate soil to the early life stages of Australian bass, Macquaria novemaculeata, incubated in seawater was evaluated. Acid-sulphate soil leachate water (pH> or =6.8) delayed the hatching of fertilised eggs, but after 48 h the per cent hatching was normal. In comparison, acidic saline water (25 per thousand salinity) at pH 4.0 or less prevented embryos from hatching. The survival of yolk-sac larvae exposed to acid-sulphate soil leachate water at a concentration of 32% in seawater and an initial pH of 7.2, was significantly different to controls after 96 hours. In corresponding tests with only acidified saline water (20 per thousand salinity), pH levels equal to or below 5.0 killed yolk-sac larvae after 96 h exposure. Aluminum showed a pH dependent toxicity to yolk-sac larvae, with added aluminium as low as 200 microg litre(-1) having a significant effect on larval survival at pH 5.5, and concentrations of 600-800 microg litre(-1) having a significant effect on larval survival at an initial pH range of 6.0 < pH < 6.8. It was concluded that significant mortality of the early life stages of Australian bass would occur if they are exposed to acid-sulphate soil leachate that results in a pH in the receiving estuarine water below 5.5, or when the pH is below 6.8 and aluminium is present at a total concentration of 800 microg litre(-1) or greater.