Effects of Gestational and Lactational Fenvalerate Exposure on Immune and Reproductive Systems of Male Rats

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Surface morphology of Diplodon expansus (Kuster, 1856; Mollusca, Bivalvia, Hyriidae) gill filaments after exposure to environmentally relevant concentrations of atrazine herbicide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Esterase inhibition in tadpoles of Scinax fuscovarius (Anura, Hylidae) as a biomarker for exposure to organophosphate pesticides

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biochemical and proteomic effects in Procambarus clarkii after chlorpyrifos or carbaryl exposure under sublethal conditions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of prenatal exposure to deltamethrin on forced swimming behavior, motor activity, and striatal dopamine levels in male and female rats

The effects of prenatal exposure of rat pups to 0.08 mg/kg deltamethrin (DTM) on physical, reflex and behavioral developmental parameters, on forced swimming and open-field behaviors, and on striatal monoamine levels at 60 days of age were observed. Maternal and offspring body weight, physical and reflex development were unaffected by the exposure to the pesticide. At 21 days of age, open-field locomotion frequency and immobility duration of male and female offspring were not different between control and exposed animals. However, male rearing frequency was increased in experimental animals. A decreased immobility latency to float and in general activity after the swimming test in male offspring was observed at adult age; no interference was detected in the float duration during the swimming test. In addition, these animals presented higher striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels without modification in dopamine (DA) levels and an increased DOPAC/DA ratio. These data indicate a higher activity of the dopaminergic system in these animals. Noradrenaline (NA) levels were increased, while MHPG levels were not detectable in the system studied. Serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels, as well as the homovanillic acid (HVA)/DA ratio, were not modified by the exposure to the pesticide. No changes were observed in swimming and open-field behaviors nor were there any changes in striatal monoamines or their metabolites in the female experimental group. In relation to the pesticide formula, the present data showing that prenatal exposure to DTM alters latency to float and the activity of striatal dopaminergic system might reflect a persistent effect of the pesticide on animal motor activity, mainly in males. on the other hand, the decrease in general activity observed in experimental male rats suggests higher levels of emotionality induced by previous exposure to the swimming behavior test in relation to control animals. Data gathered in the present study may be important for the assessment of the safety of pyrethroid insecticides. (C) 2001 Elsevier B.V. All rights reserved.

Behavioral effects of acute exposure to the insecticide fipronil

The effects of fipronil (Frontline (R) Top Spot) were investigated in 40 days old rats utilizing open field (OF), hole-board (HB) and elevated plus-maze (EPM) apparatus. Rats (N=15) received topical application of fipronil (70, 140 and 280 mg/kg) in the neck region and behavior was tested 3 h after administration. Animals treated with corn oil (vehicle) were used as controls. In the of test animals treated with fipronil at 140 mg/kg showed increased rearing, whereas animals exposed to 280 mg/kg showed increased freezing, grooming, and rearing. In the HB test fipronil at 280 mg/kg increased head-dip and head-dipping behaviors. In the EPM test the only observed effect was increased number of entries in both open and closed EPM arms in animals treated with 280 mg/kg. In conclusion, dermal exposure to fipronil causes effects related to emotionality, fear, and exploratory activity; results add strength to the growing concern that pirazole insecticides can be neurotoxic to humans. Published by Elsevier B.V.

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/Kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21- day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 ±2.0), 4 (12.3 ± 1.2) and 5 (8.7 ± 0.9) in relation to controls (10.6 ± 1.2; 4.5 ± 0.6 and 3.4 ± 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140± 11)and 17(124± 12), and 16 (104±9), 17 (137 ± 9) and 18 (106 ± 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 ± 11 and 69 ± 10 for days 16 and 17 and 49 ± 9, 48 ± 7 and 56 ± 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz- treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Neonatal rat exposure to pyrethroid and organophosphate insecticides: A physiological and biochemical trial of progeny

A manufactured product (Ectoplus®) composed by a cypermethrin (44.7%) and dichlorvos (4.2%) mixture was administered (10mg/kg/day, orally, by gavage) to pregnant rats, during the periods of gestation+lactation, gestation, and lactation. Control mothers received vehicle aqueous solution during the gestation+lactation period. With the progeny, in the 1-15 post-natal days (PNDI-15) there were observed alterations in the periods of occurrence of teeth, hair, unfolding of ears, and in the developmental period for following reflexes: postural, palmar grasp, negative geotaxis, and acoustic startle reflex. After weaning (PND21), there were observed the presence of cypermethrin and dichlorvos in the blood brain and liver; decrease in weight of liver, of cholinesterase activity in the plasma, liver, and brain, and hepatic metabolizing activity of drugs; alterations of levels of gamma glutamyl transferase enzymes, of creatinine, and of potassium in the serum of the animals. In conclusion, neonatal exposure to a formulated mixture of cypermethrin and dichlorvos is inductive to alterations in characteristics that indicate somatic and neuromuscular development of the progeny, and in certain biochemical parameters. The results suggest that enzymatic assessment associated with somatic and neuromotor assessment can be important markers of developmental characteristics in neonatal toxicity by pesticide formulations based on mixtures of insecticides.

Biochemical biomarkers in Scinax fuscovarius tadpoles exposed to a commercial formulation of the pesticide fipronil

One of the main pesticides used in the cultivation of sugarcane in São Paulo State, Brazil, is Regent®800WG, the main active compound of which is fipronil. Fipronil is a potent insecticide that eliminates pests, including insects resistant to pyrethroids, organophosphates (OP) and carbamates (CA). There is little known on the toxic effects of fipronil on non-target organisms, such as tadpoles of frogs. It is possible that this compound carries a high toxicity for these organisms, since the pesticide can be incorporated into aquatic environments during the rainy season, a time which coincides with the time of amphibian reproduction and the occurrence of tadpoles in the aquatic environment in this region. Thus, the pesticide could be contributing to the decline of amphibians in the northwest region of São Paulo state due to its wide use. This study aimed to test the influence of Regent®800WG on some biochemical systems of tadpoles (such as antioxidant defense systems) at different stages of development. The results of analysis from in vivo exposures demonstrated that only a few parameters in the groups exposed to fipronil responded to exposure to Regent®800WG, results which indicate that the pesticide instigates biochemical responses in tadpoles. Although catalase and glucose-6-phosphate dehydrogenase (G6PDH) were unchanged during the experiments, glutathione-S-transferase (GST) was inhibited in tadpoles, and the activity of glutathione reductase (GR) varied according to the exposure period and pesticide concentration. This data demonstrated the influence of the fipronil formulation on the metabolism of tadpoles, and showed that it can increase their susceptibility to environmental contaminants. © 2013 Elsevier Ltd. All rights reserved.

Procedures to Evaluate the Efficiency of Protective Clothing Worn by Operators Applying Pesticide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Absence of effects on the rat sperm quality after subacute exposure to low doses of fungicide prochloraz

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Assessment of the sublethal toxicity of organochlorine pesticide endosulfan in juvenile common carp (Cyprinus carpio)

This study is aimed at evaluating the sublethal effects of endosulfan (EDS) in juvenile common carp (Cyprinus carpio). For this purpose, fish were exposed for 15 days to the technical EDS (95% pure) diluted in dimethyl sulfoxide (DMSO) 0.1% of the total volume in water solution in a semi-static system at sublethal concentration (1 mu g/L). Subsequently, the liver somatic index (LSI) and factor condition (K) were determined. The total cytocrome P450 (CYP), CYP1A isoform, and the ethoxyresorufin-O-deethylase (EROD) activity were determined from the hepatic microsomal fraction as well as the activity of the oxidative stress enzyme system such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GP(X)), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH). Among the parameters assessed, EDS at the sublethal concentration in subchronic exposure caused significant changes in liver somatic indices as well as induction of the phase I biotransformation system and oxidative stress in juvenile common carp (Cyprinus carpio). Thus, it is seen that the use of biochemical biomarkers of environmental contamination in this study proved to be an extremely important tool for detecting the adverse effects of xenobiotics in the aquatic environment, even at low concentration.

Complex organochlorine pesticide mixtures as determinant factor for breast cancer risk: a population-based case-control study in the Canary Islands (Spain)

[EN] Background: All the relevant risk factors contributing to breast cancer etiology are not fully known. Exposure to organochlorine pesticides has been linked to an increased incidence of the disease, although not all data have been consistent. Most published studies evaluated the exposure to organochlorines individually, ignoring the potential effects exerted by the mixtures of chemicals. Methods: This population-based study was designed to evaluate the profile of mixtures of organochlorines detected in 103 healthy women and 121 women diagnosed with breast cancer from Gran Canaria Island, and the relation between the exposure to these compounds and breast cancer risk.Results: The most prevalent mixture of organochlorines among healthy women was the combination of lindane and endrin, and this mixture was not detected in any affected women. Breast cancer patients presented more frequently a combination of aldrin, dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD), and this mixture was not found in any healthy woman. After adjusting for covariables, the risk of breast cancer was moderately associated with DDD (OR = 1.008, confidence interval 95% 1.001-1.015, p = 0.024).Conclusions: This study indicates that healthy women show a very different profile of organochlorine pesticide mixtures than breast cancer patients, suggesting that organochlorine pesticide mixtures could play a relevant role in breast cancer risk.

Sublethal effects of a common neonicotinoid pesticide, thiamethoxam, on honey bees: impact on locomotion and thermoregulation

Neonicotinoids have been pointed to as a factor responsible for the increased honey bee colony losses in the last decades. Many studies have investigated the effects of the first marketed neonicotinoid, imidacloprid, while fewer have focused on thiamethoxam. One recent study showed that sublethal doses of thiamethoxam lead to colony failure by decreasing forager homing flight success. We thus decided to investigate the mechanism which caused this phenomenon. Our hypothesis was that this effect was caused by impairment of forager locomotion abilities. Therefore we tested the effects of sublethal acute and chronic exposures to thiamethoxam on forager walking (Chapter 2) and flight (Chapter 3) performances. The acute treatment (1.34 ng/bee) affected walking locomotion firstly triggering hyperactivity (30 min post-treatment) and then impairing motor functioning (60 min post-treatment). 2-day continuous exposures to thiamethoxam (32.5, 45 ppb) elicited fewer effects on walking locomotion, however both exposure modes elicited an increased positive phototaxis. Similarly, in flight experiments, the single dose (1.34 ng/bee) elicited hyperactivity shortly after intoxication (increased flight duration and distance), while longer and continuous exposures (32.5, 45 ppb) impaired forager motor functions (decreased flight duration, distance, velocity). It is known that flight muscles temperature needs to be precisely regulated by bees during flight. Therefore, we further hypothesized that the impaired flight performances of neonicotinoid intoxicated bees were caused also by thermoregulation anomalies. We tested the effects that acute thiamethoxam exposures (0.2, 1, 2 ng/bee) elicit on forager thorax temperature (Chapter 4). Foragers treated with high doses exhibited hyperthermia or hypothermia when respectively exposed to high or low environmental temperatures. In summary, we show that sublethal doses of thiamethoxam affected forager walking and flight locomotion, phototaxis and thermoregulation. We also display the intricate mode of action of thiamethoxam which triggered, at different extents, inverse sublethal effects in relation to time and dose.

Evaluation of oxidative damage and renal distal tubule cell stress response following exposure to lindane

Lindane, or γ-hexachlorocyclohexane, is a chlorinated hydrocarbon pesticide that was banned from U.S. production in 1976, but until recently continued to be imported and applied for occupational and domestic purposes. Lindane is known to cause central nervous system (CNS), immune, cardiovascular, reproductive, liver, and kidney toxicity. The mechanism for which lindane interacts with the CNS has been elucidated, and involves antagonism of the γ-aminobutyric acid/benzodiazepine (GABAA/BZD) receptor. Antagonism of this receptor results in the inhibition of Cl- channel flux, with subsequent convulsions, seizures, and paralysis. This response makes lindane a desirable defense against arthropod pests in agriculture and the home. However, formulation and application of this compound can contribute to human toxicity. In conjunction with this exposure scenario, workers may be subject to both heat and physical stress that may increase their susceptibility to pesticide toxicity by altering their cellular stress response. The kidneys are responsible for maintaining osmotic homeostasis, and are exposed to agents that undergo urinary excretion. The mechanistic action of lindane on the kidneys is not well understood. Lindane, in other organ systems, has been shown to cause cellular damage by generation of free radicals and oxidative stress. Previous research in our laboratory has shown that lindane causes apoptosis in distal tubule cells, and delays renal stress response under hypertonic stress. Characterizing the mechanism of action of lindane under conditions of physiologic stress is necessary to understand the potential hazard cyclodiene pesticides and other organochlorine compounds pose to exposed individuals under baseline conditions, as well as under conditions of physiologic stress. We demonstrated that exposure to lindane results in oxidative damage and dysregulation of glutathione response in renal distal tubule (MDCK) cells. We showed that under conditions of hypertonic stress, lindane-induced oxidative stress resulted in early onset apoptosis and corresponding down-regulated expression of the anti-apoptotic protein, Bcl-xL. Thus, the interaction of lindane with renal peripheral benzodiazepine receptors (PBR) is associated with attenuation of cellular protective proteins, making the cell more susceptible to injury or death. ^