Teratogenic effects of the fungicide maneb on chick embryos

The teratogenicity of a commercial formulation of the fungicide maneb (Maneb 80, containing 80% manganese ethylenebisdithiocarbamate and 20% inert ingredients) in chick embryos was evaluated. Unincubated eggs (157-207 per treatment group) were immersed in 0.5, 1.5, 4.5, or 13.5 g/liter maneb aqueous solutions for 30 sec. Two control groups were used: one group of 200 eggs was immersed in tap water and a second group of 205 eggs was immersed in a solution of the inert ingredients (sodium lignin sulfonate and n-butylnaphthalene sulfonate) at the concentration present in the 13.5 g/liter maneb solution. Eggs were then incubated for 19 days. A single treatment with maneb was teratogenic at all concentrations tested, producing mainly unilateral lower limb deformities. No adverse effects on development were noticed after exposure to the inert ingredients.     

Teratogenic studies of fenitrothion on white leghorn chick embryos

Summary Teratogenic studies of fenitrothion, an organophosphorus insecticide were conducted on White Leghorn chick embryos. Fenitrothion injections of 5 to 30% concentration in 0.1 ml volumes into the egg yolk space during 4th to 12th day of incubation were lethal to the embryos and the concentration of 0.1, 0.5 and 1.0% resulted in 40, 35 and 30% hatch, respectively. The chicks showed visible abnormalities such as dwarfism, curled toe, lag weakness and abnormal gait. Fenitrothion injections were comparatively less toxic during the later stages of embryonic development (8th to 12th day of incubation). The growth rate of chicks hatched from fenitrothion treated eggs was reduced as compared to the control chicks (distilled water treated).     

Cytogenetic effects of methylmercury in embryos of the killifish,Fundulus heteroclitus

Fertilized eggs of the killifish,Fundulus heteroclitus, were exposed experimentally to methylmercury (MeHg) to evaluate whether this compound induced cytogenetic effects expressed in the embryos. An additional objective was to assess cytogenetically whetherFundulus embryos from groups that were determined to be more susceptible to the teratogenic effects of MeHg were also more susceptible to its mutagenic effects. Embryos exposed to 0.05 mg/L MeHg for 1 and 7 days post-fertilization were preserved in 10% formalin for cytological examination, while unfixed embryos from the same clutches were evaluated for teratogenic effects. Untreated embyros from each clutch served as controls. Cytogenetic-cytological analyses of fixed treated susceptible embryos that exhibited teratogenic effects revealed decreased mitotic counts (5.0-fold), and increased chromosomal aberrations (2.5-fold) when compared to their controls. There were also decreased mitotic counts (1.5-fold) and increased chromosomal aberrations (2-fold) in embryos from resistant groups when compared to their controls. Exposure to MeHg also retarded development. Forty to fifty percent of the susceptible and resistant control embryos reached the tail-bud stage, but only 28% of the treated resistant and none of the treated susceptible embryos reached this stage. There was also a significant correlation (P < 0.05) between teratogenic and mutagenic effects of MeHg in early stages ofFundulus.     

Teratogenic effects of amitraz, 2,4-dimethylaniline,and paraquat on developing frog (Xenopus) embryos

Developmental effects of amitraz (acaricide), its metabolite (2,4-dimethylaniline), and paraquat (herbicide) on embryos of a nontarget organism, Xenopus laevis, were investigated. Following the standard protocol of the American Society for Testing and Materials (ASTM), the experiments were carried out using native Xenopus frogs. There was a drastic increase in mortality from 24 h to 96 h for paraquat, but 2,4-dimethylaniline showed no mortality at the highest concentration tested (100 mg/L). The 96-h LC₅₀ values were 0.67, 3.27, and ≫100 mg/L for paraquat, amitraz, and 2,4-dimethylaniline, respectively. At concentrations higher than 0.2 mg/L of paraquat all the embryos were malformed, whereas growth reduction was apparent at all test concentrations (0.1–5 mg/L). The most common teratogenic effects were flexures of the notochord and stunting of growth. Edema was the most common effect of amitraz on the embryos, and 100% of the surviving embryos in 5 mg/L were edematous. The 96-h EC₅₀ (malformation) values were 1.21 (95% CI 0.48–3.03) and 0.18 (95% CI 0.16–0.20) mg/L for amitraz and paraquat, respectively. The ratio of 96-h LC₅₀ to 96-h EC₅₀ (malformation), i.e., the teratogenicity index (TI) were 2.7 and 3.72 for amitraz and paraquat, respectively, and for 2,4-dimethylaniline (TI > 5) all the embryos in 25 mg/L showed observable pigment loss and encephalomegaly. This shows that paraquat and the degradation product of amitraz, 2,4-dimethylaniline, should be classified as teratogens. Teratogenic risks of massive application of these pesticides on Kenyan farms should therefore be considered. Received: 27 June 2001/Accepted: 4 February 2002     

Interactions between methylmercury and selenomethionine injected into mallard eggs

Methylmercury chloride and seleno-L-methionine were injected separately or in combinations into mallard eggs (Anas platyrhynchos), and embryo mortality and teratogenic effects (deformities) were modeled using a logistic regression model. Methylmercury was injected at doses that resulted in concentrations of 0, 0.2, 0.4, 0.8, and 1.6?μg/g Hg in the egg on a wet weight basis and selenomethionine at doses that resulted in concentrations of 0, 0.1, 0.2, 0.4, and 0.6?μg/g Se in the egg, also on a wet weight basis. When selenomethionine and methylmercury were injected separately, hatching probability decreased in both cases. However, when methylmercury was injected at 1.6?μg/g in combination with selenomethionine at 0.2?μg/g, the presence of the methylmercury resulted in less embryo mortality than had been seen with 0.2?μg/g Se by itself, but it increased the number of deformed embryos and hatchlings. Selenomethionine appeared to be more embryotoxic than equivalent doses of methylmercury when injected into eggs, and both injected methylmercury and selenomethionine were more toxic to mallard embryos than when deposited naturally in the egg by the mother. The underlying mechanisms behind the interactions between methylmercury and selenomethionine and why methylmercury appeared to improve hatching probability of Se-dosed eggs yet increased deformities when the two compounds were combined are unclear. These findings warrant further studies to understand these mechanisms in both laboratory and field settings.     

Teratogenic and toxic effects of alcohol ethoxylate and alcohol ethoxy sulfate surfactants on Xenopus laevis embryos and tadpoles

The two surfactants tested, an alcohol ethoxylate (AE) and an alcohol ethoxy sulfate (AES), demonstrate both teratogenic and toxic effects in Xenopus laevis embryos and tadpoles. From acute tests and observations of malformations under light and electron microscopy, the AES produced less teratogenic and toxic effects than the AE, from which it differs only by the presence of a sulfate in the hydrophilic group of the molecule. The 72-h LC(50) was 4.59 mg/L for the AE and 6.75 g/L for the AES. The tissues most affected were the epithelia, particularly of the gills. As the AE exhibited ultrastructural alterations of mitochondria and narcotic effects, O(2) consumption was studied in treated tadpoles; results indicated collapse of the electrochemical gradient in mitochondria.     

Toxicity of methylmercury injected into eggs when dissolved in water versus corn oil

In a previous study, the embryotoxicity of methylmercury dissolved in corn oil was compared among 26 species of birds. Corn oil is not soluble in the water-based matrix that constitutes the albumen of an egg. To determine whether the use of corn oil limited the usefulness of this earlier study, a comparison was made of the embryotoxicity of methylmercury dissolved in corn oil versus water. Mallard (Anas platyrhynchos) and chicken (Gallus gallus) eggs were injected with methylmercury chloride dissolved in corn oil or water to achieve concentrations of 0, 0.2, 0.4, 0.8, and 1.6 μg/g mercury in the egg on a wet weight basis. Hatching success at each dose of mercury was compared between the two solvents. For mallards, 16.4% of the eggs injected with 1.6 μg/g mercury dissolved in water hatched, which was statistically lower than the 37.6% hatch rate of eggs injected with 1.6 μg/g mercury dissolved in corn oil, but no differences in hatching success were observed between corn oil and water at any of the other doses. With chicken eggs, no significant differences occurred in percentage hatch of eggs between corn oil and water at any of the mercury doses. Methylmercury dissolved in corn oil seems to have a toxicity to avian embryos similar to that of does methylmercury dissolved in water. Consequently, the results from the earlier study that described the toxicity of methylmercury dissolved in corn oil to avian embryos were probably not compromised by the use of corn oil as a solvent.     

文冠果种仁对SD大鼠的致畸作用

目的研究文冠果种仁对SD大鼠的致畸作用。方法于SPF级SD大鼠孕期第6～15天,经口灌胃给予孕鼠文冠果种仁2. 0、4. 0和8. 0 g/kg,并于分娩前1天处死母鼠,剖检检查母鼠受孕和仔鼠发育情况。对骨骼行茜素红染色并进行检查,对内脏进行Bouins液固定并检查。结果文冠果种仁各剂量组的母体体重、体重增重、子宫连胎重、体重净增重,着床数、黄体数、吸收胎数、活胎数、死胎数及百分率,胎鼠外观、骨骼、内脏的单项畸胎率和总畸胎率,以及有畸形胎仔的窝百分率等,与阴性对照组比较差异无统计学意义(P>0. 05)。结论在该实验条件下,文冠果种仁对妊娠SD大鼠无母体毒性,对胎鼠无致畸性和胚胎发育毒性,其母体毒性的未观察到有害作用剂量(NOAEL)和胎鼠的最小致畸剂量>8. 0 g/kg。     

Developmental and methylmercury effects on brain protein synthesis

Sprague-Dawley rats (ages 1 to 21 days, alternate days) were chosen for study. Animals were injected with methylmercuric chloride (8 mg/kg IP); 12 hr later each animal was injected with uniformly labeled L-(¹⁴C)leucine, allowed 30 min for incorporation, and decapitated. Brains were analyzed for amounts of radioactivity incorporated into TCA precipitable protein. When compared to baseline curves for control animals, curves of treated animals were compressed overall and had age-dependent increases and decreases in rates of protein synthesis.     

Evidence on the human health effects of low-level methylmercury exposure

Background: Methylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by bene-ficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited.Objectives: We undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide.Data sources and extraction: We reviewed the published literature for original human epidemio-logic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon).Data synthesis: Recent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent.Conclusions: Studies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.     

Neurotoxic and molecular effects of methylmercury in humans

Mercurials are global environmental pollutants deriving from natural processes and anthropogenic activities. Most human exposure to mercury occurs through the intake of fish, shellfish, and sea mammals contaminated with methylmercury. Methylmercury is bioaccumulated and biomagnified in the aquatic food chain and reaches its highest levels in top predatory fish. The neurotoxic hazard posed by methylmercury to humans and the unique susceptibility of the developing brain have been well documented following the mass poisonings occurring in Japan and Iraq. Adult cases of methylmercury poisoning are characterized by the delayed onset of symptoms and by the focal degeneration of neurons in selected brain regions (for example, cerebral cortex and cerebellum). Why the fetus displays different neuropathological effects and a higher sensitivity to methylmercury relative to the adult is still unknown. Depending on the degree of in utero exposure, methylmercury may result in effects ranging from fetal death to subtle neurodevelopmental delays. On the basis of epidemiological studies performed in populations having moderate chronic methylmercury exposure, no definitive consensus has been reached to date on the safety level of maternal exposure during pregnancy. Among the multiple mechanisms believed to contribute to methylmercury neurotoxicity, methylmercury-induced microtubule alterations, oxidative damage, impairment of calcium homeostasis, and the potentiation of glutamatergic neurotransmission are presented in this review.     

Teratogenic effects of lithium and ethanol in the developing fetus

Prolonged administration of either lithium (7 mg/kg body wt.) or ethanol (30% of daily caloric intake) for 10 days to pregnant rats results in several anatomical abnormalities in the fetus. Intragastric administration of lithium carbonate to pregnant rats immediately after confirmation of pregnancy resulted in high incidence of cleft palate, growth retardation, brain liquification and pulpy brain, hepatomegaly and digital abnormalities, when compared to the saline-treated controls. Furthermore, lithium administration during gestation also resulted in other less frequently observed abnormalities in the fetus, e.g., cardiomegaly, hydronephrosis, ankle-joint defects, syndactyly, defected ribs and sternum ossification defects. Chronic ethanol consumption by pregnant rats during early gestation also resulted in several anatomical abnormalities of prenatal growth retardation, resorption and still births, cleft palate, hydrocephaly and hydronephrosis. The severity and frequency of several of the fetal abnormalities were compounded when lithium and ethanol were administered simultaneously. The possible mechanisms of lithium and ethanol teratogenicity and their synergistic effects have been explained on a biochemical basis.     

Long-term exposure to methylmercury and its effects on hypertension in Minamata

Recent studies suggest potential adverse effects of methylmercury exposure on cardiovascular disease, although the evidence of association with hypertension is still inconsistent. Therefore, we evaluated the effects of methylmercury exposure on hypertension in Minamata. We used data derived from the 1971 population-based survey in Minamata and neighboring communities. We also utilized data on hair mercury content of the participants (derived from a 1960 investigation). We adopted two exposure indices (residential area and hair mercury content) and two hypertension outcomes (past history of hypertension and hypertension defined by measurements in the examination). Then, we estimated the adjusted prevalence odds ratio (POR) and its confidence interval (CI) of both hypertension outcomes in relation to residential area and hair mercury content. In the Minamata area (high exposure area), 87% (833) of the eligible population (aged ≥10 years) participated in the 1971 investigations. In the Goshonoura area (middle exposure area) and the Ariake area (low exposure area), 93% (1450) and 77% (755), respectively, of the eligible population participated. Compared with subjects in the Ariake area, the subjects in the Minamata area manifested hypertension more frequently, and PORs observed for two hypertension outcomes were 1.6 (95% CI: 1.2-2.1) and 1.4 (95% CI: 1.1-1.9), respectively. Furthermore, dose-response trends with hair mercury content were observed for both hypertension outcomes. The present finding supports the causal relationship between methylmercury exposure and hypertension.