Animals ; Humans ; Neurotoxins ; toxicity ; Pesticides ; toxicity ; Pyrethrins ; toxicity ; Toxicology

Animals ; Female ; Pregnancy ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar ; Teratogens ; toxicity

As a new type of pesticides and because of their high performance and low toxicity, pyrethroid insecticides are widely used in place of organochlorine insecticides both in agriculture and in the home. In the recent years, more and more evidence indicates that pyrethroid insecticides can reduce sperm count and motility, cause deformity of the sperm head, increase the count of abnormal sperm, damage sperm DNA and induce its aneuploidy rate, as well as affect sex hormone levels and produce reproductive toxicity. The present article reviews the advances in the studies of male reproductive toxicity of pyrethroid pesticides by experiment in animals and human population, discusses the mechanism of male reproductive toxicity of pesticides and raises some problems concerning the evaluation of human reproductive hazards.
Animals ; Genitalia, Male ; drug effects ; pathology ; physiopathology ; Humans ; Insecticides ; poisoning ; toxicity ; Male ; Mice ; Pyrethrins ; poisoning ; toxicity ; Rats ; Toxicity Tests

OBJECTIVETo explore the effects of rat maternal exposure to fenvalerate during lactation on behaviors development in rat pubertal female offspring.

METHODSTwelve ICR maternal mice were randomly divided into 7.5 and 30.0 mg/kg fenvalerate exposure groups and control group (four dams each group, ten pups each dam, half male half female, twenty female pups each group). The exposure groups were orally exposed to fenvalerate at the doses of 7.5 and 30 mg/kg a day from postnatal day 1 (PND1) to PND21. The control group was exposed to corn oil. The effects of maternal fenvalerate exposure during lactation on motor and species-typical behaviors in female offspring were observed on the PND 35.

RESULTSThe peripheral time and standing frequency of 30.0 mg/kg exposure group were (263.4 ± 54.8) s and (47.3 ± 16.2) times, which were significantly higher than those [(203.4 ± 53.0) s and (30.9 ± 17.3) times] of control group (P < 0.05). The scores in 7.5 mg/kg and 30.0 mg/kg exposure groups were 56.50 ± 50.79 and 54.73 ± 53.91, respectively, which were significantly lower than that (114.53 ± 53.87) in control group (P < 0.05). However, no significant differences in beam walking scores, food hoarding quantity, food digging quantity, and nest construction scores between two exposure groups were found (P > 0.05).

CONCLUSIONThe rat maternal exposure to fenvalerate during lactation could decrease the ability of exploration and motor condition and increase the anxiety but not affect life habit in rat pubertal female offspring.

Animals ; Behavior, Animal ; Female ; Male ; Maternal Exposure ; Mice ; Mice, Inbred ICR ; Nitriles ; toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; Pyrethrins ; toxicity

OBJECTIVETo study the effects of pyrethroids on the activity of gamma-aminobutyric acid transferase (GABAT) in rat brain.

METHODThe coupled enzyme ultraviolet spectrophotography was applied to observe the effects of deltamethrin (DM) and permethrin (PM) on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum in vitro and in vivo.

RESULTSIn vitro, DM and PM had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum at the final concentration of 10(-9) - 10(-4) mol/L. When 37.5 mg/kg DM and 600 mg/kg PM were orally administrated to the rats at one time, the activities of GABAT in rat cerebral cortex, hippocampus and cerebellum in the DM group [(2.96 +/- 0.43), (2.13 +/-0.44), (5.12 +/- 1.36) nmol x mg pro(-1) x min(-1), respectively] were lower than those in the control group [(3.43 +/- 0.41), (2.68 +/- 0.47), (6.74 +/- 1.64) nmol x mg pro(-1) x min(-1)] (P < 0.05), and the activities of GABAT in rat cerebral cortex and hippocampus in the PM group [(4.57 +/- 0.30), (4.18 +/- 0.63) nmol.mg pro(-1) x min(-1), respectively] were higher than those in the control group (P < 0.05). When 12.5 mg/kg DM and 200 mg/kg PM were orally administrated to the rats once a day for consecutive five days, the two pesticides had no significant effects on the activities of GABAT in rat cerebral cortex, hippocampus, corpus striatum and cerebellum (P > 0.05).

CONCLUSIONSIn vitro, DM and PM had no significant effects on the activity of GABAT in rat brain; in vivo, DM and PM may have different effects on the activity of GABAT in rat brain, which deserve further study.

Animals ; Brain ; drug effects ; enzymology ; In Vitro Techniques ; Insecticides ; toxicity ; Male ; Pyrethrins ; toxicity ; Rats ; Spectrophotometry ; Transferases ; metabolism ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo study the effects of deltamethrin (DM) on cell survival rate and intracellular Ca(2+) ([Ca(2+)]i) concentration in primary cultured astrocytes of rat.

METHODSThe cell survival rate was measured by Typan Blue assay; the intracellular [Ca(2+)]i concentration was determined by the fluorescent Ca(2+) indicator Fura-2/AM.

RESULTSThe survival rate of astrocytes was decreased to 91.9% after astrocytes were incubated with 1 x 10(-5) mol/L DM for 72 h (P < 0.05). The cell survival rates were 89.0%, 84.8%, 81.2% and 79.2% respectively when astrocytes were administered with 1 x 10(-4) mol/L DM for 4, 12, 24 and 72 h, which were remarkably lower than control groups (P < 0.01). Comparing with controls and before DM treatment, sharp increases in [Ca(2+)]i concentration [(451.4 +/- 42.3), (536.9 +/- 47.5) and (870.9 +/- 100.5) nmol/L respectively] were observed when astrocytes were incubated with 1 x 10(-7), 1 x 10(-6) and 1 x 10(-5) mol/L DM for 5 minutes (P < 0.01). After astrocytes were treated with 1 x 10(-8), 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) mol/L DM for 15 minutes, the [Ca(2+)]i concentrations were decreased to (124.3 +/- 6.0), (131.3 +/- 19.1), (118.9 +/- 1.4), (136.6 +/- 3.8) nmol/L respectively, which were significantly different from those of controls and before treatment. And this situation was almost keeping stable to 30 min.

CONCLUSIONThe cell survival rate was decreased and the [Ca(2+)]i concentration was temporarily increased when astrocytes were treated with DM.

Animals ; Astrocytes ; cytology ; drug effects ; metabolism ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Insecticides ; toxicity ; Nitriles ; Pyrethrins ; toxicity ; Rats

OBJECTIVETo study the protective effect of MG-132 on hippocampus cells apoptosis induced by deltamethrin (DM), one kind of pyrethroid pesticide.

METHODS40 Male wistar rats were randomly divided into four groups: olive oil control, DM treated alone (12.5 mg/kg), MG-132 (0.5 mg/kg) plus DM group, MG-132 treated 2h plus olive oil. After 24h treatment of DM, the hippocampus was taken out to detect the apoptotic cell rate, the level of bcl-2 and Caspase-3 activity.

RESULTSCompared with DM treated alone group (27.29% +/- 2.41%), the apoptotic cell rate in MG-132 + DM group (19.94% +/- 2.07%) was increased (P < 0.05), bcl-2 expression was enhanced [(0.43 +/- 0.06) vs. (2.01 +/- 0.23)] (P < 0.05) and the activity of Caspase-3 was decreased significantly (P < 0.05) in MG-132 treated 2h plus DM group [(4.55 +/- 0.46) vs.(3.73 +/- 0.35)].

CONCLUSIONMG-132 can protect hippocampus cells against apoptosis induced by deltamethrin.

Animals ; Apoptosis ; drug effects ; Hippocampus ; cytology ; drug effects ; Insecticides ; toxicity ; Leupeptins ; pharmacology ; Male ; Neurons ; drug effects ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo observe the direct effects of fenvalerate (Fen) on sperm motility in SD rats.

METHODSSperm were isolated from caudal epididymides of healthy adult male rats with the diffusion method. The motility parameters of the isolated sperm, such as VCL, VSL, VAP, BCF, STR and LIN, were monitored by computer-assisted sperm analysis (CASA) system after 1, 2 and 4 h Fen-exposure in vitro at concentrations of 0, 1, 4, 16 and 64 micromol/L respectively.

RESULTSAfter 1 and 2 h Fen-exposure, VSL, BCF, STR and LIN decreased significantly at 64 micromol/L compared with the control group. After 4 h Fen-exposure, the motility parameters VCL, VSL, BCF, STR and LIN dropped progressively at 64 micromol/L, and VCL declined markedly at 16 micromol/L. However, only VCL and STR showed alterations in a time-response manner.

CONCLUSIONFen may affect the caudal epididymal sperm and produce a direct toxic effect on sperm motility in SD rats.

Animals ; Dose-Response Relationship, Drug ; Insecticides ; toxicity ; Male ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; drug effects

Adverse drug reactions constitute a major public health problem. In recent years, serious safety issues arose with marketed drugs, and public outcry demanded better safety surveillance. Now regulatory focus is shifting to the active post-marketing safety surveillance. This paper provides an overview of the recent international initiatives of drug safety management especially focused on the US and Europe. The US Food and Drug Administration's (FDA) Sentinel Initiative is a long-term program designed to build and implement a national electronic system for monitoring the safety of FDA-approved drugs and other medical products. The Sentinel System will enable FDA to monitor the safety of medical products with the assistance of a wide array of collaborating institutions throughout the nation. The European Network of Centers for Pharmacoepidemiology and Pharmacovigilance is a collaborative scientific network coordinated by the European Medicines Agency and developed in collaboration with European experts in the fields of pharmacoepidemiology and pharmacovigilance. Its goal is to further strengthen the post-marketing monitoring of medicinal products in Europe by facilitating the conduct of multi-center, independent, post-authorization studies focusing on safety and on benefit-risk. Medicine is a global enterprise that demands worldwide standards for good drug safety practices. In the near future, we have to establish a Korean Sentinel System for active post-marketing safety surveillance to ensure the safety and effectiveness of drugs used in medical practice.
Cooperative Behavior ; Dietary Sucrose ; Drug Toxicity ; Electronics ; Electrons ; Europe ; Nitriles ; Organothiophosphorus Compounds ; Pharmacoepidemiology ; Pharmacovigilance ; Public Health ; Pyrethrins ; Safety Management

OBJECTIVETo explore the effect of maternal cypermethrin exposure during lactation on learning and memory ability in adult female offspring, as well as the possible mechanism.

METHODSTwelve maternal mice were randomly divided into 6.25 mg/kg cypermethrin, 25.0 mg/kg cypermethrin and control groups (four dams each group, ten pups each dam, half male half female, twenty female pups each group). Maternal mice were orally administered with different doses of cypermethrin (6.25 and 25 mg/kg/d) once daily from postnatal day1 (PND1) to PND21. Maternal mice in control group were treated with corn oil. The learning and memory ability of female offspring were observed by using water labyrinth task for continuously seven days on PND60. All the female offspring were killed and the brain and hippocampus were detached after the test. The expression level of NMDA receptor NR1 protein in hippocampus was detected by Western-blotting.

RESULTSThere were no statistically significant in the difference in weight of body and brain among three groups (P > 0.05). Through the Repeated one way ANOVA, the learning time of latency in the 25.0 mg/kg cypermethrin group [(31.3 ± 17.0) s] were significantly longer than that in the control group [(21.0 ± 14.0) s] (P < 0.05). The memory time of latency in the 25.0 mg/kg cypermethrin group [(24.6 ± 21.1) s] were significantly longer than that in the control group [(14.1 ± 16.3) s] (P < 0.05). However, the difference of the wrong number among groups was not statistically significant in the test (P > 0.05).

CONCLUSIONMaternal cypermethrin exposure during lactation disturbs learning and memory ability in adult female offspring in a degree, which maybe caused by the reduction of protein level of hippocampus NR1.

Animals ; Animals, Newborn ; Female ; Male ; Maternal Exposure ; Maze Learning ; Memory ; Mice ; Mice, Inbred ICR ; Pregnancy ; Pyrethrins ; toxicity