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1.
Food Chem Toxicol ; 190: 114790, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38849044

RESUMO

Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo, male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21-60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro, HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 µg/mL) for 24 h. And the results showed that CCC above 120 µg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.


Assuntos
Proteínas Quinases Ativadas por AMP , Clormequat , Fígado Gorduroso , Lipogênese , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR , Animais , Serina-Treonina Quinases TOR/metabolismo , Masculino , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Lipogênese/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Células Hep G2 , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Ratos , Clormequat/toxicidade , Ratos Sprague-Dawley , Fígado/efeitos dos fármacos , Fígado/metabolismo
2.
Toxicol Lett ; 395: 17-25, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38552810

RESUMO

Since chlormequat chloride is widely applied as a plant growth regulator in agriculture and horticulture, its exposure through food consumption is common. We demonstrated previously that chlormequat chloride exposure during pregnancy led to embryos with bigger sizes associated with higher levels of growth hormone (GH) on gestation day 11 (GD11). However, the dose-effect relationship of chlormequat chloride at a lower dose range was not established, and the underlying mechanisms of its promoting effects on embryonic growth and development were not fully elucidated. To address these, pregnant rats were orally exposed to chlormequat chloride at 0, 0.05, 0.5 and 5 mg/kg.bw from GD0 to 11 and the embryonic growth and growth related hormones were evaluated on GD11. We found that the growth and development of the embryos was significantly promoted in a dose dependent manner by chlormequat chloride. Chlormequat chloride also increased embryonic GH, GH releasing hormone (GHRH), and somatostatin (SRIF), and inhibited the embryonic cAMP dependent protein kinase A (PKA) signaling pathway. Chlormequat chloride increased GH synthesis modulated by GHRH/SRIF-PKA-Pituitary specific transcription factor 1 (Pit-1) in the maternal rats. Intriguingly, chlormequat chloride did not show any effects on GH and PKA signaling pathways in the non-pregnant female rats. These findings together suggest that the disrupting effect of chlormequat chloride on GH is associated with pregnancy.


Assuntos
Clormequat , Hormônio do Crescimento , Gravidez , Feminino , Ratos , Animais , Hormônio do Crescimento/metabolismo , Clormequat/toxicidade , Reguladores de Crescimento de Plantas/toxicidade , Fatores de Transcrição , Transdução de Sinais
3.
Ecotoxicol Environ Saf ; 274: 116193, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460407

RESUMO

Chlorocholine chloride (CCC) is a plant growth regulator used worldwide that is detectable in cereals, fruits and animal products. The health effects of CCC exposure have raised public concern. Our previous research showed that CCC exposure decreased testosterone synthesis in pubertal rats. However, little is known about whether and how pubertal CCC exposure impacts spermatogenesis. In this study, we used BALB/c mice and spermatogonia-derived GC-1 cells to examine CCC-induced spermatogenic dysfunction. In vivo, pubertal CCC exposure led to decreased testicular weight, decreased testicular germ cells and poor sperm quality. This effect worsened after cessation of CCC exposure for the next 30 days. RNA-seq and western blot analysis revealed that CCC induced aryl hydrocarbon receptor (AhR) signaling, endoplasmic reticulum stress (ERS) and ferritinophagy. Increased iron content and lipid peroxidation levels were also observed in CCC-treated testes. In vitro, it was identified that iron overload mediated by enhanced ferritinophagy occurred in CCC-treated GC-1 cells, which might be attributed to the PERK pathway in ERS. Further, for the first time, our study elucidated the involvement of AhR in CCC-induced iron overload, which aggravated testicular oxidative damage via lipid peroxidation. Considering the adverse impact of CCC exposure on rodents, supportive evidence from GC-1 cells, and the critical importance of spermatogenesis on male development, the effects of CCC on the male reproduction warrant increased attention.


Assuntos
Acetatos , Clormequat , Sobrecarga de Ferro , Fenóis , Espermatogênese , Animais , Masculino , Camundongos , Ratos , Clormequat/metabolismo , Clormequat/toxicidade , Sobrecarga de Ferro/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Sementes , Espermatogênese/efeitos dos fármacos , Testículo , eIF-2 Quinase/efeitos dos fármacos , eIF-2 Quinase/metabolismo
4.
Toxicol Lett ; 356: 161-171, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34958886

RESUMO

Chlorocholine chloride (CCC) is well acknowledged as a plant growth regulator and may be considered as a potential environmental endocrine disrupting chemical. In our previous studies, it was found that CCC exposure at a pubertal stage reduced the serum and testicular levels of testosterone, decreased the sperm motility and delayed the puberty onset. However, the molecular mechanisms of CCC-induced testosterone secretion disorders remain unclear. In this study, we found that CCC exposure above 20 µg/mL inhibited the secretion of testosterone in Sprague-Dawley rats Leydig cells. Proteomic and pathway enrichment analysis indicated that CCC might induce endoplasmic reticulum (ER) stress. Western blot detection showed CCC exposure at 100, 200 µg/mL increased the protein level of glucose-regulated protein 78 (GPR78), C/EBP-homologous protein (CHOP), the ubiquitin-conjugating enzyme E2 D1 (UBE2D1) and the ring finger protein (RNF185) in the Leydig cells. The Leydig cells treated with 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, rescued the testosterone secretion disorders and alleviated CCC-induced increase in the ER stress related protein levels at 200 µg/mL CCC treatment. Overall, CCC in vitro exposure might disturb testosterone production of Leydig cells and endoplasmic reticulum stress was involved in it.


Assuntos
Clormequat/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Testosterona/metabolismo , Animais , Sobrevivência Celular , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Mapas de Interação de Proteínas , Ratos , Ratos Sprague-Dawley
5.
Toxicol Lett ; 351: 28-36, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34411681

RESUMO

Chlorocholine chloride (CCC) promote plant growth as a regulator. Emerging evidence by our group showed that CCC might restrain the puberty onset and impair the reproductive functions in male rats through HPT axis. In this study, we further investigated the effects of prenatal CCC exposure on pubertal development, reproduction of male offspring in rats and explored the underlying mechanisms. The results showed that CCC of 137.5 and 200 mg/kg bw/day delayed the age of preputial separation (PPS), decreased the sperm motility of male offspring. PP1γ2 which is an essential protein in spermatogenesis reduced in 137.5 and 200 mg/kg bw/day groups. Crucial hormones involved in hypothalamic-puititary-testicular (HPT) axis decreased at postnatal day (PND) 30. It was indicated that CCC exposure in pregnancy might disturb the pubertal development, reproductive functions of male offspring through HPT axis and disturb the sperm motility through PP1γ2.


Assuntos
Clormequat/toxicidade , Infertilidade Masculina/induzido quimicamente , Reguladores de Crescimento de Plantas/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Maturidade Sexual/efeitos dos fármacos , Animais , Feminino , Masculino , Gravidez , Ratos , Análise do Sêmen , Motilidade dos Espermatozoides/efeitos dos fármacos
6.
Toxicology ; 442: 152534, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32622971

RESUMO

We showed previously that chlormequat chloride, a widely used plant growth regulator, could affect embryonic growth and growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis of rats. However, the potential effects of low dose chlormequat chloride exposure during pregnancy on embryonic and postnatal growth and development remain unclear. To further assess the risk of chlormequat chloride to human embryonic growth and postnatal health, we exposed maternal rats orally to the chemical during pregnancy at 5 mg/kg bw, a dose corresponding to the human acceptable daily intake (ADI) level set by World Health Organization (WHO), and determined the effects of chlormequat on embryo growth and postnatal health. We found that chlormequat chloride increased embryonic growth parameters, GH, and GH-releasing hormone (GHRH) levels, but did not affect somatostatin and IGF-1 on gestational day (GD) 11. In the pups of postnatal day (PD) 7, we observed increased head length, decreased body fat percentage, hypoglycemia, hyperlipidemia and hyperproteinemia. In conclusion, maternal exposure to chlormequat chloride during pregnancy disrupts the embryonic growth probably through its effects on growth regulators and even has adverse effects on postnatal health.


Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Clormequat/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/biossíntese , Hormônio Liberador de Hormônio do Crescimento/biossíntese , Fator de Crescimento Insulin-Like I/biossíntese , Masculino , Exposição Materna , Reguladores de Crescimento de Plantas/toxicidade , Gravidez , Ratos , Ratos Sprague-Dawley , Somatostatina/biossíntese
7.
Toxicol Lett ; 319: 1-10, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689472

RESUMO

Chlorocholine chloride (CCC), a plant growth retardant, may act as an endocrine disruptor. Our previous study showed that pubertal CCC exposure in rats might decrease testosterone (T) synthesis. This study observed the changes in pubertal development and reproduction of male rats exposed to CCC and its underlying mechanisms. Rats were exposed to CCC (0, 75, 137.5 and 200 mg/kg bw/day) from postnatal day 23 to 60. The results showed that CCC treatment delayed the onset of puberty and reduced the relative organ weight of prostate. Seminiferous tubules with deciduous spermatogenic cells were observed in the 200 mg/kg bw/day group. Sexual behavior was inhibited in the 137.5 and 200 mg/kg bw/day groups. Sperm motility, litter size and normalized anogenital distance (AGD) of male pups were decreased in the 137.5 and 200 mg/kg bw/day groups. Serum kisspeptin level and serum and testicular levels of T were reduced in all CCC treated groups. Crucial hormones in hypothalamic-pituitary-testicular (HPT) axis were reduced subsequently after CCC treatment. Collectively, our results demonstrated that CCC might disturb HPT axis through suppressing the secretion of kisspeptin and subsequently lead to delayed puberty onset and impaired reproductive functions.


Assuntos
Clormequat/toxicidade , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Genitália/anatomia & histologia , Genitália/efeitos dos fármacos , Genitália/crescimento & desenvolvimento , Hormônios Esteroides Gonadais/sangue , Kisspeptinas/metabolismo , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/crescimento & desenvolvimento , Ratos , Ratos Sprague-Dawley , Túbulos Seminíferos/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testosterona/sangue
8.
Reprod Toxicol ; 89: 115-123, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301413

RESUMO

Litter size and other conventional measures in rodents are common end-points in the assessment of xenobiotics for reprotoxic effects. However, since litter size may be normal despite reduced semen quality, we established and tested a mouse in vitro fertilization/in vitro culture (IVF/IVC) system to assess other aspects of reprotoxicity of xenobiotic exposure. Two pesticides, vinclozolin (V) and chlormequat (C), were added to feed in low (40 and 900 ppm, respectively) and high (300 and 2700 ppm, respectively) doses and compared to control (nil pesticide). Exposed males were used for natural mating to evaluate litter size and then used for IVF/IVC and sperm evaluation. The IVF/IVC system detected significant adverse effect of high dose of vinclozolin on blastocyst formation, which was not detected by conventional measures such as litter size or sperm motility and viability. We conclude that assessment based on IVF/IVC measures may complement litter size and other conventional end-points.


Assuntos
Oócitos/efeitos dos fármacos , Exposição Paterna/efeitos adversos , Reprodução/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Xenobióticos/toxicidade , Animais , Clormequat/toxicidade , Relação Dose-Resposta a Droga , Feminino , Fertilização in vitro , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos , Oxazóis/toxicidade , Gravidez , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos
9.
Toxicol Lett ; 288: 17-24, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29447956

RESUMO

Chlorocholine chloride (CCC) is widely used to regulate plant growth. Considerable attention has been focused on its reproductive and developmental toxicities. In order to investigate the effects of pubertal CCC exposure on testicular testosterone (T) synthesis, male SD rats were exposed to CCC by oral gavage at doses of 0, 75, 150 and 300 mg/kg bw/day from postnatal day 23 to 70. We observed that pubertal CCC exposure lowered the body weight and the mean Johnsen's score. The percentage of seminiferous tubules with deciduous spermatogenic cells was increased in the 75 and 150 mg/kg bw/day groups. In addition, pubertal CCC exposure reduced the testicular absolute weights in the 75 and 300 mg/kg bw/day groups as well as the sperm motility in epididymides in the 150 mg/kg bw/day group. A significant decrease of testicular T was observed while levels of hypothalamic gonadotropin-releasing-hormone (GnRH) and serum luteinizing hormone (LH) were increased. Protein levels of steroidogenic acute regulatory (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were decreased. Taken together, these results indicate that pubertal CCC exposure in rats might decrease testicular T synthesis by suppressing the expression of steroidogenic enzymes, which partially lead to an impairment on spermatogenesis.


Assuntos
Clormequat/toxicidade , Esteroides/biossíntese , Testículo/metabolismo , Testosterona/biossíntese , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Masculino , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Túbulos Seminíferos/efeitos dos fármacos , Maturidade Sexual , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Esteroides/antagonistas & inibidores , Testículo/efeitos dos fármacos , Testículo/enzimologia , Testosterona/antagonistas & inibidores
10.
Toxicology ; 381: 1-9, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28214531

RESUMO

Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage.


Assuntos
Clormequat/toxicidade , Condrócitos/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Esqueleto/efeitos dos fármacos , Animais , Peso Corporal , Densidade Óssea/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo I/sangue , Relação Dose-Resposta a Droga , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Hormônio do Crescimento/metabolismo , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteocalcina/sangue , Osteoclastos/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Peptídeos/sangue , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Esqueleto/crescimento & desenvolvimento , Tíbia/efeitos dos fármacos , Tíbia/metabolismo
11.
Environ Toxicol Pharmacol ; 47: 92-99, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27653211

RESUMO

Chlormequat Chloride (CCC) is a plant growth regulator that is widely applied in agriculture. Previous studies have shown that long-term exposure of CCC could decrease body weight in animals. However, the underlying mechanisms have not been studied. In this study, CCC was administered to rats daily by gavage on postnatal days 23-60 at doses of 0, 75, 150 and 300mg/kg bw/d. The results showed that body weight and the length of the right femur were significantly decreased in the 300mg/kg bw/d group. Histological analysis of proximal growth plates of the right femurs showed narrowed proliferative zones and hypertrophic zones in CCC-treated groups. The mRNA expression of growth hormone, growth hormone receptor and insulin like growth factor 1 were decreased in the CCC-treated group. The results indicated that CCC may affect the expression of growth hormone and insulin-like growth factor 1 and subsequently cause a decrease in body weight and bone length.


Assuntos
Peso Corporal/efeitos dos fármacos , Clormequat/toxicidade , Hormônio do Crescimento/sangue , Acetilcolina/sangue , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Lâmina de Crescimento/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/genética , Masculino , Tamanho do Órgão/efeitos dos fármacos , Reguladores de Crescimento de Plantas/toxicidade , Puberdade/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores da Somatotropina/genética
12.
Toxicol In Vitro ; 34: 274-282, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27165806

RESUMO

Chlormequat chloride is the most widely used plant growth regulator in agriculture to promote sturdier growth of grain crops by avoidance of lodging. Therefore, human exposure to chlormequat chloride is very common, but its developmental toxicity has not been studied. Thus, we investigated the developmental toxicity of chlormequat chloride by applying rat whole embryo culture (WEC) model, limb bud micromass culture and 3T3 fibroblast cytotoxicity test. Chlormequat chloride at 150µg/ml (0.93mM) retarded the rat embryo growth without causing significant morphological malformations and at 500µg/ml (3.1mM) caused both retardation and morphological malformation of the embryos. However, the proliferation and differentiation of limb bud cells were not affected by chlormequat chloride at as high as up to 1000µg/ml (6.2mM) applied. This concentration of chlormequat chloride did not affect the cell viability as examined by 3T3 fibroblast cytotoxicity test either, suggesting that cellular toxicity may not play a role in chlormequat induced inhibition of rat embryo growth. Collectively, our results demonstrated that chlormequat chloride may affect embryo growth and development without inhibiting cell viability.


Assuntos
Clormequat/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Reguladores de Crescimento de Plantas/toxicidade , Teratogênicos/toxicidade , Células 3T3 , Animais , Sobrevivência Celular/efeitos dos fármacos , Membro Anterior/embriologia , Membro Posterior/embriologia , Botões de Extremidades/efeitos dos fármacos , Camundongos , Ratos Sprague-Dawley
13.
Food Chem Toxicol ; 59: 438-45, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23822974

RESUMO

¹H Nuclear Magnetic Resonance spectroscopy has been used to profile urinary metabolites in male Fischer F344 rats in order to assess the metabolic changes induced by oral exposure to two benzimidazole fungicides (carbendazim and thiabendazole) and two bipyridyllium herbicides (chlormequat and mepiquat). Exposure levels were selected to be lower than those expected to cause overt signs of toxicity. We then compared the sensitivity of the metabolomics approach to more traditional methods of toxicity assessment such as the measurement of growth and organ weights. Separate, acute exposure experiments were conducted for each pesticide to identify potential metabolic markers of exposure across four doses (and a control). Growth, organ weights and feeding/drinking rates were not significantly affected by any compounds at any dose levels tested. In contrast, metabolic responses were detected within 8 and 24h for chlormequat and mepiquat, and after 24h for carbendazim and thiabendazole. These results demonstrate the potential for the use of metabolomics in food toxicity testing.


Assuntos
Contaminação de Alimentos , Fungicidas Industriais/farmacocinética , Herbicidas/farmacocinética , Metabolômica/métodos , Resíduos de Praguicidas/farmacocinética , Toxicologia/métodos , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/análise , Benzimidazóis/farmacocinética , Benzimidazóis/toxicidade , Biomarcadores/urina , Carbamatos/administração & dosagem , Carbamatos/análise , Carbamatos/farmacocinética , Carbamatos/toxicidade , Clormequat/administração & dosagem , Clormequat/análise , Clormequat/farmacocinética , Clormequat/toxicidade , Relação Dose-Resposta a Droga , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/análise , Fungicidas Industriais/toxicidade , Herbicidas/administração & dosagem , Herbicidas/análise , Herbicidas/toxicidade , Espectroscopia de Ressonância Magnética , Masculino , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/toxicidade , Resíduos de Praguicidas/urina , Piperidinas/administração & dosagem , Piperidinas/análise , Piperidinas/farmacocinética , Piperidinas/toxicidade , Análise de Componente Principal , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Tiabendazol/administração & dosagem , Tiabendazol/análise , Tiabendazol/farmacocinética , Tiabendazol/toxicidade , Reino Unido
14.
Int J Androl ; 29(1): 129-33, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16466532

RESUMO

This paper summarizes the consequences of exposure to chlormequat, a plant growth regulator, on reproduction in mammals. Plant growth regulators are chemicals used to manipulate plant growth, flowering and fruit yield. In grain crops, plant growth regulators are applied to promote sturdier growth and reduce the risk of lodging. Chlormequat is the most common plant growth regulator. Maximum residue limits of chlormequat in food products are 10 mg/kg in oat and pear, 3 mg/kg in wheat and rye, and 0.5 mg/kg in milk. In Denmark, results from experiments with pigs in the late 1980s showed sows that display impaired reproduction, mainly impaired oestrus, when fed grain from crop treated with chlormequat. Subsequently, the advisory body to the Danish pig industry recommended limiting the use of grain (maximum 30% of diet energy) from crop treated with chlormequat given to breeding stock due to the risk of reproduction problems. More recently, experiments have been conducted to evaluate the influence of chlormequat-treated wheat crop on reproductive function in male and female mice. These experiments showed that epididymal spermatozoa from mice on feed or water containing chlormequat had compromised fertilizing competence in vitro, while reproduction in female mice was not compromised. The estimated intake of chlormequat in the pig (0.0023 mg/kg bw/day) and the mouse (0.024 mg/kg bw/day) experiments was below the acceptable daily intake of 0.05 mg/kg bw/day. Reports from the industry do not show any effects at these low levels.


Assuntos
Clormequat/toxicidade , Fertilidade/efeitos dos fármacos , Reguladores de Crescimento de Plantas/toxicidade , Espermatozoides/efeitos dos fármacos , Animais , Feminino , Fertilidade/genética , Humanos , Masculino , Camundongos , Espermatozoides/citologia , Suínos
15.
Environ Sci Technol ; 39(7): 2406-13, 2005 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15871283

RESUMO

Environmental assessments in pesticide product development are generally restricted to plant uptake and emissions of active ingredients. Life-cycle assessment (LCA) enables a more comprehensive evaluation by additionally assessing the impacts of pesticide production and application (e.g. tractor operations). The use of LCA in the product development of pesticides, in addition to the methods commonly applied, is therefore advisable. In this paper a procedure for conducting LCA in early phases of product development is proposed. In a case study, two plant-growth regulators from different product generations were compared regarding their application in intensive production of winter wheat. The results showed thatthe reduced emissions from active ingredients of the newer pesticide were compensated by higher impacts from the production process. The authors draw the conclusion that it is important to consider environmental objectives in the procurement of precursors, in addition to the classical goals of increasing the efficacy and reducing the nontarget effects of pesticides. Moreover, the case study showed that decisions based on uncertain results in early stages of product development may need to be revised in later stages, e.g. based on investigations of pesticides' effects on crop yield.


Assuntos
Meio Ambiente , Praguicidas/toxicidade , Medição de Risco/economia , Medição de Risco/métodos , Clormequat/química , Clormequat/toxicidade , Qualidade de Produtos para o Consumidor/normas , Ciclopropanos/química , Ciclopropanos/toxicidade , Tomada de Decisões , Quinonas/química , Quinonas/toxicidade , Triticum/efeitos dos fármacos , Triticum/crescimento & desenvolvimento
16.
Reprod Toxicol ; 13(5): 399-404, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10560589

RESUMO

The aim of this study was to evaluate the influence of feeding with food and water containing chlorocholinechloride (CCC) on the fertility of male mice in a two-generation study. For this purpose the number of testicular spermatozoa and the relative proportion of primary and secondary spermatocytes involved in spermatogenesis were measured. Furthermore, the fertility of epididymal spermatozoa from tested male mice was investigated in a special in-vitro fertilization system. The experimental food was composed of CCC-treated wheat in the first experiment and CCC-free wheat and water mixed with pure CCC in the second experiment. The CCC residue content in the treated food and water was 0.21 mg/kg and 0.2 mg/L, respectively. Under the influence of feeding with CCC-treated wheat (Experiment 1) the fertilization and cleavage rates of oocytes incubated with spermatozoa from CCC-fed mice were reduced: the fertilization rate 65.1% vs. 21.1% and the cleavage rate 51.9% vs. 20.3%, p < 0.01 (control feeding vs. CCC feeding, respectively). Feeding of sperm donors with pure CCC mixed with untreated wheat pellets or water (Experiment 2) led to a reduction in the fertilization and cleavage rate (control: 60.8%, 32.4%; CCC-food: 29.8%, 12.1%; CCC-water: 30.1%, 10.2%; CCC-food/water: 36.6%, 12.5%; p < 0.01, respectively). The normal course of spermatogenesis was unchanged after the exposure to CCC. Testicular weight, the number of spermatozoa, and the proportion of haploid, diploid, and tetraploid testicular cells were not influenced. However, the functional competence of epididymal spermatozoa from CCC-fed donors was reduced, resulting in a significantly diminished fertilization and cleavage rate in vitro. The results suggest that CCC could interfere with epididymal protein secretion and the process of sperm maturation during passage through the epididymis.


Assuntos
Clormequat/toxicidade , Fertilidade/efeitos dos fármacos , Fertilização in vitro , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Triticum/efeitos dos fármacos , Administração Oral , Ração Animal/análise , Animais , Clormequat/análise , Fase de Clivagem do Zigoto/fisiologia , DNA/genética , Feminino , Fertilidade/genética , Citometria de Fluxo , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/genética , Masculino , Camundongos , Oócitos/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Exposição Paterna , Ploidias , Contagem de Espermatozoides , Espermatozoides/citologia , Testículo/efeitos dos fármacos , Testículo/patologia , Abastecimento de Água/análise
17.
Vet Med (Praha) ; 29(11): 699-704, 1984 Nov.
Artigo em Eslovaco | MEDLINE | ID: mdl-6084359

RESUMO

The toxic effect of the following pesticides was examined: metathion (doses from 1.49 micrograms to 100.0 g per litre of medium), phenmedipham (doses from 24.42 micrograms to 400.0 mg per litre of medium), gamma-hexachlorocyclohexane (doses from 122.07 micrograms to 250.0 mg per litre of medium), and chlormequat (doses from 305.16 micrograms to 20.0 g per litre of medium). The tests were performed on the protozoan Tetrahymena pyriformis. The LD50 of metathion was found to be 8.94 micrograms per litre and the LD100 ranged from 23.84 to 47.68 micrograms per litre. In phenmedipham the LD50 ranged from 12.5 to 25.0 mg per litre and its LD100 was above 400.0 mg per litre. The LD50 of gamma-hexachlorocyclohexane is 976.56 micrograms per litre and LD100 about 7.91 mg per litre. The LD50 of chlormequat ranged from 312.5 to 625.0 mg per litre and LD100 was about 20.0 g per litre of medium.


Assuntos
Inseticidas/toxicidade , Tetrahymena pyriformis/efeitos dos fármacos , Carbamatos/toxicidade , Clormequat/toxicidade , Fenitrotion/toxicidade , Hexaclorocicloexano/toxicidade
18.
Toxicology ; 31(1): 67-71, 1984 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-6729837

RESUMO

We investigated the effects of chlorocholine chloride (CCC), a plant growth regulator, and cyclophosphamide (CP), a known immunosuppressant, on the ability of deer mice (Peromyscus maniculatus) to resist challenge with a sublethal dose of Venezuelan equine encephalitis virus ( VEEV ). The toxicants were continuously delivered in low doses in the feed; CP at 20 mg/kg body wt/day and CCC at 1, 10, 20 or 40 mg/kg body wt/day. Mice were inoculated with 3 X 10(4) plaque forming units (pfu) of VEEV after eating experimental feed for 23 days. Mice were bled daily for 7 days and at selected intervals from 8 to 63 days post inoculation (PI) for viremia and antibody titer determinations. CP treatment increased the duration of viremia and significantly (P less than or equal to 0.05) decreased mean viremia titers. Antibody titers were significantly (P less than or equal to 0.05) depressed in CP-treated mice compared to controls. CP treatment increased mortality. CCC had no effect on viremia duration or titer except when given in doses of 1 mg/kg body wt/day when it significantly (P less than or equal to 0.05) decreased mean viremia titers compared to controls. Early antibody responses were increased by CCC treatment except in the 10 mg/kg body wt/day treatment group in which titers were decreased. By 30 days PI antibody titers of CCC-treated mice were no different from controls.


Assuntos
Clormequat/toxicidade , Ciclofosfamida/toxicidade , Encefalomielite Equina/imunologia , Encefalomielite Equina Venezuelana/imunologia , Reguladores de Crescimento de Plantas/toxicidade , Compostos de Amônio Quaternário/toxicidade , Animais , Anticorpos Antivirais/análise , Camundongos , Peromyscus , Viremia/imunologia
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