Pterocarpus mildbraedii leaf extract ebbs propanil-induced oxidative and apoptotic damage in the liver of rats.

Phytochemicals derived from plant sources are well recognized as sources of pharmacologically potent drugs in the treatment of several oxidative stress-related ailments. Dichloromethane/methanol (1:1) leaf extract of Pterocarpus mildbraedii was evaluated for its possible protection against oxidative stress and apoptosis in the liver of male Wistar rats exposed to propanil (PRP). In the experimental design, olive oil served as the vehicle, and rats were grouped into control (2 mL/kg olive oil), PRP (200 mg/kg/day), Pterocarpus mildbraedii extract (200 mg/kg/day), and Pterocarpus mildbraedii extract (200 mg/kg/day)+PRP (200 mg/kg/day), and treated daily, p.o., for seven days. Oxidative stress parameters, B-cell lymphoma 2 (Bcl-2), Bcl 2-associated X protein (Bax), p53, caspases (9/3), and terminal transferase dUTP nick end labeling (TUNEL) assays were observed in all groups. Propanil significantly elevated superoxide dismutase and lipid peroxidation levels, while concomitantly depleting GSH and p53 levels. Further, PRP enhanced the expressions of caspase-9, caspase-3, Bax, and TUNEL-positive cells in the liver of rats. However, these observed alterations were reversed following treatment with Pterocarpus mildbraedii extract. Our studies suggest that Pterocarpus mildbraedii extract protected against PRP toxicity by reducing oxidative stress and attenuating critical endpoints in the intrinsic apoptotic pathway.

Analysis of serum levels of organochlorine pesticides and related factors in Parkinson's disease.

BACKGROUND: There is evidence that environmental factors contribute to the onset and progression of Parkinson's disease (PD). Pesticides are a class of environmental toxins that are linked to increased risk of developing PD. However, few studies have investigated the association between specific pesticides and PD, especially in China, which was one of the first countries to adopt the use of pesticides. METHODS: In this study, serum levels of 19 pesticides were measured in 90 patients with PD and 90 healthy spouse controls. We also analyzed the interaction between specific pesticides and PD. In addition, the association between pesticides and clinical features of PD was also investigated. Finally, we investigated the underlying mechanism of the association between pesticides and PD. RESULTS: Serum levels of organochlorine pesticides, which included α-hexachlorocyclohexane (HCH), ß-HCH, γ-HCH, δ-HCH, propanil, heptachlor, dieldrin, hexachlorobenzene, p,p'-dichlorodiphenyltrichloroethane and o,p'-dichloro-diphenyl-trichloroethane were higher in PD patients than controls. Moreover, α-HCH and propanil levels were associated with PD. Serum levels of dieldrin were associated with Hamilton Depression Scale and Montreal Cognitive Assessment scores in PD patients. In SH-SY5Y cells, α-HCH and propanil increased level of reactive oxygen species and decreased mitochondrial membrane potential. Furthermore, propanil, but not α-HCH, induced the aggregation of α-synuclein. CONCLUSIONS: This study revealed that elevated serum levels of α-HCH and propanil were associated with PD. Serum levels of dieldrin were associated with depression and cognitive function in PD patients. Moreover, propanil, but not α-HCH, induced the aggregation of α-synuclein. Further research is needed to fully elucidate the effects of pesticides on PD.

Identifying major pesticides affecting bivalve species exposed to agricultural pollution using multi-biomarker and multivariate methods.

The aim of this investigation was to identify major pesticides that may cause detrimental effects in bivalve species affected by agricultural pollution. Investigations were carried out using freshwater clams (Corbicula fluminea) transplanted in the main drainage channels that collect the effluents coming from agriculture fields in the Ebro Delta (NE Spain) during the main growing season of rice (from May to August). Environmental hazards were assessed by measuring simultaneous up 46 contaminant levels and 9 biomarker responses. Measured biological responses showed marked differences across sites and months. Antioxidant and esterase enzyme responses were in most cases inhibited. Lipid peroxidation levels increased steadily from May in upstream stations to August in drainage channels. Principal Component (PCA) and Partial Least Squares to Latent Structure regression (PLS) analyses allowed the identification of endosulfan, propanil, and phenylureas as being the chemical contaminants causing the most adverse effects in the studied species.

Cytogenotoxic effect of propanil using the Lens culinaris Med and Allium cepa L test.

Propanil can produce methemoglobinemia, hemolytic anemia, hepatotoxicity, metabolic disorder and nephrotoxicity. It also has a genotoxic effect, although it is not listed as a carcinogen and it continues to be applied excessively throughout the world. Consequently, in this study the cytogenotoxic effect of propanil was evaluated, using apical root cells of Allium cepa and Lens culinaris. In which, L. culinaris seeds and A. cepa bulbs were subjected to 6 treatments with propanil (2, 4, 6, 8, 10 and 12 mg L-1) and to distilled water as control treatment. Subsequently, the root growth was measured every 24 h for 3 days. Next, the mitotic index and cellular anomalies were determined. Whereby, decreased root development was observed in all treatments. Likewise, greater inhibition of mitosis was evidenced in L. culinaris compared to A. cepa. In addition, chromosomal abnormalities, such as nucleus absence, sticky chromosomes in metaphase and binucleated cells, were present in most of the treatments. Thus, the presence of micronuclei and the results of L. culinaris, indicate the high cytogenotoxicity of propanil and the feasibility of this species as bioindicator.

Effects of propanil on the European eel Anguilla anguilla and post-exposure recovery using selected biomarkers as effect criteria.

The aim of this study was to assess the physiological response of Anguilla anguilla to propanil and the degree of recovery after being moved to clean water. Preliminary acute toxicity test was carried out in the laboratory and the median lethal concentration (LC50) at 96 h was calculated as 31.33 mg/L (29.60-33.59 mg/L). NOEC and LOEC values (at 96 h) were also calculated as 20 and 25mg/L, respectively. The fish were exposed to 0.63 and 3.16 mg/L of propanil for 72 h and allowed to recover for 144 h. Total proteins (TPs), gamma-glutamil transpeptidase (gamma-GT), alanin aminotransferase (AlAT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and water content (WC) were assayed in muscle and liver tissues, liver somatic index (LSI) was also determined. Liver TPs and gamma-GT activity decreased after propanil exposure while AlAT and LDH increased. Muscular AP, AlAT and proteins decreased in intoxicated eels while LDH and gamma-GT activities increased. WC increased in both tissues after herbicide exposure as well as LSI. These results revealed that propanil affects the intermediary metabolism of A. anguilla and that the assayed enzymes can be used as good biomarkers of herbicide contamination. However a longer recovery period should be necessary to re-establish eel physiology. The parameters measured in the present study can be used as herbicide toxicity indicators and are recommended for environmental monitoring assessments.

Toxicity evaluation of three pesticides on non-target aquatic and soil organisms: commercial formulation versus active ingredient.

The Ecological Risk Assessment of pesticides requires data regarding their toxicity to aquatic and terrestrial non-target species. Such requirements concern active ingredient(s), generally not considering the noxious potential of commercial formulations. This work intends to contribute with novel information on the effects of short-term exposures to two herbicides, with different modes of action (Spasor, Stam Novel Flo 480), and an insecticide (Lannate), as well as to corresponding active ingredients (Glyphosate, Propanil and Methomyl, respectively). The microalga Pseudokirchneriella subcapitata (growth inhibition), the cladoceran Daphnia magna (immobilisation), and the earthworm Eisenia andrei (avoidance behaviour) were used as test species. Both herbicides were innocuous to all test organisms at environmentally realistic concentrations, except for Stam and Propanil (highly toxic for Pseudokirchneriella; moderately toxic to Daphnia). Lannate and Methomyl were highly toxic to Daphnia and caused Eisenia to significantly avoid the spiked soil at realistic application rates. The toxicity of formulations either overestimated (e.g. Stam/Propanil for P. subcapitata) or underestimated (e.g. Stam/Propanil for D. magna) that of the active ingredient.

In vitro nephrotoxicity induced by propanil.

Propanil is a postemergence herbicide used primarily in rice and wheat production in the United States. The reported toxicities for propanil exposure include methemoglobinemia, immunotoxicity, and nephrotoxicity. A major metabolite of propanil, 3,4-dichloroaniline (3,4-DCA), has been shown to be a nephrotoxicant in vivo and in vitro, but the nephrotoxic potential of propanil has not been examined in detail. The purpose of this study was to determine the nephrotoxic potential of propanil using an in vitro kidney model, determine whether in vitro propanil nephrotoxicity is due to metabolites arising from propanil hydrolysis, and examine mechanistic aspects of propanil nephrotoxicity in vitro. Propanil, 3,4-DCA, propionic acid (0.1-5.0 mM), or vehicle was incubated for 15-120 min with isolated renal cortical cells (IRCC; approximately 4 million cells/mL) obtained from untreated male Fischer 344 rats. Cytotoxicity was determined by measuring lactate dehydrogenase release from IRCC. In 120-min incubations, propanil induced cytotoxicity at concentrations >0.5 mM. At 1.0 mM, propanil induced cytotoxicity following 60- or 120-min exposure. Cytotoxicity was observed with 3,4-DCA (2.0 mM) at 60 and 120 min, while propionic acid (5.0 mM) induced cytotoxicity at 60 min. In IRCC pretreated with an antioxidant, cytochrome P450(CYP) inhibitor, flavin adenine dinucleotide monooxygenase activity modulator, or cyclooxygenase inhibitor before propanil exposure (1.0 mM; 120 min), only piperonyl butoxide (0.1 mM), a CYP inhibitor, pretreatment decreased propanil cytotoxicity. These results demonstrate that propanil is an in vitro nephrotoxicant in IRCC. Propanil nephrotoxicity is not primarily due to metabolites resulting from hydrolysis of propanil, but a metabolite resulting from propanil oxidation may contribute to propanil cytotoxicity.

3,4-dichloropropionaniline suppresses normal macrophage function.

Macrophages are a critical part of the innate immune response and natural surveillance mechanisms. As such, proper macrophage function is crucial for engulfing bacterial pathogens through phagocytosis and destroying them by generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The production of a number of cytokines by macrophages, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, plays an important role in the initiation of the acquired immune response creating an inflammatory environment favorable for fighting a bacterial infection. 3,4-Dichloropropionaniline (DCPA) suppresses several inflammatory parameters, including TNF-alpha production through a mechanism where nuclear factor-kappaB (NF-kappaB)-DNA binding is inhibited but not entirely abrogated. The goal of the present study was to evaluate the effects of DCPA on the inflammatory mediators of macrophages, including ROS and RNS in both murine peritoneal exudate cells and the human monocytic cell line, THP-1. The ability to perform phagocytosis and directly kill Listeria monocytogenes was also assessed. The results indicate that DCPA decreases the ability of both types of macrophages to phagocytize beads and generate both types of reactive species, which was correlated with a decrement in listericidal activity. These results demonstrate that DCPA has profound effects on macrophage function and provide insight into the potential mechanisms of immunosuppression by DCPA.

Propanil exposure induces delayed but sustained abrogation of cell-mediated immunity through direct interference with cytotoxic T-lymphocyte effectors.

The postemergent herbicide propanil (PRN ; also known as 3,4-dichloropropionanilide) is used on rice and wheat crops and has well-known immunotoxic effects on various compartments of the immune system, including T-helper lymphocytes, B lymphocytes, and macrophages. It is unclear, however, whether PRN also adversely affects cytotoxic T lymphocytes (CTLs) , the primary (1 degrees ) effectors of cell-mediated immunity. In this study we examined both the direct and indirect effects of PRN exposure on CTL activation and effector cell function to gauge its likely impact on cell-mediated immunity. Initial experiments addressed whether PRN alters the class I major histocompatibility complex (MHC) pathway for antigen processing and presentation by antigen-presenting cells (APCs) , thereby indirectly affecting effector function. These experiments demonstrated that PRN does not impair the activation of CTLs by PRN-treated APCs. Subsequent experiments addressed whether PRN treatment of CTLs directly inhibits their activation and revealed that 1 degrees alloreactive CTLs exposed to PRN are unimpaired in their proliferative response and only marginally inhibited in their lytic activity. Surprisingly, secondary stimulation of these alloreactive CTL effectors, however, even in the absence of further PRN exposure, resulted in complete abrogation of CTL lytic function and a delayed but significant long-term effect on CTL responsiveness. These findings may have important implications for the diagnosis and clinical management of anomalies of cell-mediated immunity resulting from environmental exposure to various herbicides and other pesticides.

Evidence for a novel endocrine disruptor: the pesticide propanil requires the ovaries and steroid synthesis to enhance humoral immunity.

Steroid hormones are known to affect the humoral immune response to a variety of antigens. However, the mechanisms regulating these effects are poorly understood. The immunotoxic chemical propanil and estrogen have similar effects on the immune system including augmentation of humoral immune responses. Propanil enhances the number of phosphorylcholine (PC)-specific IgG2b, IgG3, and IgM antibody-secreting cells (ASCs) in the spleen four- to sixfold 7 days after vaccination of female C57BL/6 mice with heat-killed Streptococcus pneumoniae. Several experiments were performed to test the hypothesis that propanil increases the response via an estrogenic pathway. Ovariectomy abrogated the effect of propanil on the PC-specific ASC response. Both in vitro and in vivo assays indicate that propanil does not bind either estrogen receptor (ER) alpha or beta. Exogenous estradiol administration in ovariectomized mice failed to restore the effect of propanil on the PC response. Treatment of female mice with a pure ER antagonist, ICI 182,780, or the progesterone antagonist RU486 did not inhibit the increase in ASCs. These data suggest that estrogen and progesterone do not regulate the effect of propanil. However, complete inhibition of steroid synthesis with the gonadotropin-releasing hormone (GnRH) antagonist antide abrogated the increased response in propanil-treated mice, indicating a necessary role for steroid synthesis. Experiments in male mice demonstrated that propanil increased the number of ASCs comparable to female mice. However, orchiectomy did not inhibit this effect, suggesting that androgens do not regulate the amplification of the humoral response. These data suggest a novel role for the ovarian hormones in the regulation of the PC-specific antibody response.

Growth rate effects, responses of antioxidant enzymes and metabolic fate of the herbicide Propanil in the aquatic plant Lemna minor.

Propanil (3,4-dichloropropionanilide) is a selective contact pesticide, recommended for post-emergence use in rice. This herbicide may end up in surface waters and present potential risk for aquatic vascular plants. Therefore, its toxicity was evaluated on Lemna minor L., an aquatic plant regularly used for toxicological studies, during time- and concentration-dependent exposure. Toxicity assessments were based on inhibition of growth of L. minor cultures after 24 days. The obtained results showed that the growth of Lemna was affected by the herbicide. The responses of the guaiacol peroxidase (G-POD) and glutathione S-transferase (GST) involved in the xenobiotic metabolism and antioxidative system were also investigated following Propanil exposure. Our results showed that Propanil has not induced enzymatic antioxidative defenses of L. minor. Both 3,4-dichloroaniline (3,4-DCA) and 3,4-dichloroacetanilide are the major metabolites in this plant. On the contrary, only 3,4-DCA was found in culture media after 4 days. Probably, the enzymatic hydrolysis by acyl acylamidase and the acetylation by acetyl-CoA are the major pathways for these transformation products, respectively. The results of this study showed that the selected aquatic plant has the potential to accumulate and metabolize rice herbicide, like Propanil. Based on these toxicity data this herbicide should impair the establishment of non-target aquatic plants.

The metabolite 3,4,3',4'-tetrachloroazobenzene (TCAB) exerts a higher ecotoxicity than the parent compounds 3,4-dichloroaniline (3,4-DCA) and propanil.

3,4,3',4'-tetrachloroazobenzene (TCAB) is not commercially manufactured but formed as an unwanted by-product in the manufacturing of 3,4-dichloroaniline (3,4-DCA) or metabolized from the degradation of chloranilide herbicides, like propanil. While a considerable amount of research has been done concerning the toxicological and ecotoxicological effects of propanil and 3,4-DCA, limited information is available on TCAB. Our study examined the toxicity of TCAB in comparison to its parent compounds propanil and 3,4-DCA, using a battery of bioassays including in vitro with aryl hydrocarbon receptor (AhR) mediated activity by the 7-ethoxyresorufin-O-deethylase (EROD) assay and micro-EROD, endocrine-disrupting activity with chemically activated luciferase gene expression (CALUX) as well as in vivo with fish embryo toxicity (FET) assays with Danio rerio. Moreover, the quantitative structure activity response (QSAR) concepts were applied to simulate the binding affinity of TCAB to certain human receptors. It was shown that TCAB has a strong binding affinity to the AhR in EROD and micro-EROD induction assay, with the toxic equivalency factor (TEF) of 8.7×10(-4) and 1.2×10(-5), respectively. TCAB presented to be a weak endocrine disrupting compound with a value of estradiol equivalence factor (EEF) of 6.4×10(-9) and dihydrotestosterone equivalency factor (DEF) of 1.1×10(-10). No acute lethal effects of TCAB were discovered in FET test after 96h of exposure. Major sub-lethal effects detected were heart oedema, yolk malformation, as well as absence of blood flow and tail deformation. QSAR modelling suggested an elevated risk to environment, particularly with respect to binding to the AhR. An adverse effect potentially triggering ERß, mineralocorticoid, glucocorticoid and progesterone receptor activities might be expected. Altogether, the results obtained suggest that TCAB exerts a higher toxicity than both propanil and 3,4-DCA. This should be considered when assessing the impact of these compounds for the environment and also for regulatory decisions.

Combined Effects of Pesticides and Trematode Infections on Hourglass Tree Frog Polypedates cruciger.

The impact of widespread and common environmental factors, such as chemical contaminants, on infectious disease risk in amphibians is particularly important because both chemical contaminants and infectious disease have been implicated in worldwide amphibian declines. Here we report on the lone and combined effects of exposure to parasitic cercariae (larval stage) of the digenetic trematode, Acanthostomum burminis, and four commonly used pesticides (insecticides: chlorpyrifos, dimethoate; herbicides: glyphosate, propanil) at ecologically relevant concentrations on the survival, growth, and development of the common hourglass tree frog, Polypedates cruciger Blyth 1852. There was no evidence of any pesticide-induced mortality on cercariae because all the cercariae successfully penetrated each tadpole host regardless of pesticide treatment. In isolation, both cercarial and pesticide exposure significantly decreased frog survival, development, and growth, and increased developmental malformations, such as scoliosis, kyphosis, and also edema and skin ulcers. The combination of cercariae and pesticides generally posed greater risk to frogs than either factor alone by decreasing survival or growth or increasing time to metamorphosis or malformations. The exception was that lone exposure to chlorpyrifos had higher mortality without than with cercariae. Consistent with mathematical models that suggest that stress should increase the impact of generalist parasites, the weight of the evidence from the field and laboratory suggests that ecologically relevant concentrations of agrochemicals generally increase the threat that trematodes pose to amphibians, highlighting the importance of elucidating interactions between anthropogenic activities and infectious disease in taxa of conservation concern.

The polysaccharide antibody response after Streptococcus pneumoniae vaccination is differentially enhanced or suppressed by 3,4-dichloropropionanilide and 2,4-dichlorophenoxyacetic acid.

Propanil (3,4-dichloropropionanilide) and 2,4-D (2,4-dichlorophenoxyacetic acid) are commonly used herbicides that have toxic effects on the immune system. The present study determined the effect of exposure to these chemicals on the immune response to a bacterial vaccine. The antibody responses to the T-independent type 2 antigen, phosphorylcholine (PC) and the T-dependent antigen, pneumococcal surface protein A (PspA) were characterized in C57BL/6 mice after heat-killed Streptococcus pneumoniae (HKSP) immunization and single or mixture herbicide exposure. Propanil exposure significantly increased the number of PC-specific IgM, IgG2b, and IgG3 antibody-secreting B cells (ASC) in the spleen 4-6-fold over control animals in a dose-dependent manner. However, the number of ASC in the bone marrow and serum titers were comparable in control and propanil-treated mice. In contrast, 2,4-D exposure decreased the number of PC-specific IgM and IgG bone marrow ASC 2-3-fold from control animals. The decrease in bone marrow ASC in 2,4-D-treated mice corresponded to a 3-4-fold decrease in PC-specific IgM, IgG2b, and IgG3 serum titers compared to control mice. The number of ASC in the spleens of 2,4-D-treated mice was, however, comparable to control mice. The antibody response to PspA was not affected by any of the treatments. There were no mixture interactions between the two herbicides in any of the responses measured. These results characterize the primary PC-specific antibody response in the bone marrow, spleen, and serum after HKSP vaccination and herbicide exposure. The differential effects of propanil and 2,4-D on the antibody response to a bacterial vaccine demonstrate the potential of chemical exposure to augment or suppress immune responses to vaccines and infectious diseases.

Inhibitory effect of 3,4-dichloro-propionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction.

Our previous studies demonstrated that both in vivo and in vitro 3,4-dichloro-propionanilide (propanil) exposure inhibited interleukin-6 (IL-6) and tumor necrosis factor (TNF) production by adherent thioglycollate-elicited peritoneal cells (macrophages) after lipopolysaccharide (LPS) stimulation. In this study, we report that IL-6 and TNF-alpha message is reduced by propanil in a concentration-dependent pattern, yet the stability of cytokine mRNA is not affected. In addition, exposure of macrophages to propanil after a relatively short period of LPS stimulation significantly reduced the production of IL-6 and TNF. Determination of the intracellular Ca2+ levels demonstrates that LPS-induced Ca2+ release is abrogated in propanil-treated macrophages. However, the binding of LPS to macrophages is not affected. Measurement of inositol 1,4,5-triphosphate (IP3) demonstrates that propanil significantly increases the level and the duration of IP3 in macrophages. These results suggest that the inhibitory effect of propanil on macrophage cytokine production is associated with the early stages of LPS-mediated signal transduction in macrophages.

Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides.

3,4-Dichloropropionanilide (propanil) and 2,4-dichlorophenoxyacetic acid (2,4-D) are two commonly used herbicides that are marketed as a chemical mixture. It was hypothesized that the interaction between these two herbicides, when administered as a mixture, would result in a greater effect on the immune system than the individual components of the mixture. The present study demonstrates in a murine model that a mixture of propanil and 2,4-D, when compared to single herbicide exposures, exacerbates decreases in thymocyte populations 2 d postexposure and inhibits the repopulation of T-cells in the thymus 7 d postexposure. Exposure to 150 mg herbicide/kg body weight of propanil or 2,4-D alone had no effect on thymus weight. In contrast, decreases in the ratio of thymus weight to body weight (TW:BW) occurred 2 d after treatment with the mixture of 150 mg propanil/kg body weight + 150 mg 2,4-D/kg body weight (150/150). Thymic atrophy was associated with a decrease in the double-positive thymocyte population (CD4+CD8+) and correlated with sera corticosterone levels from 600 to 1000 pg/ml. Therefore, the hypothesis was tested that glucocorticoids, induced after exposure to herbicides, were responsible for the thymic atrophy and depletion of thymocytes. However, similar levels of corticosterone were induced after exposure to 50, 100, or 150 mg propanil/kg body weight, and 50/50 or 100/100 mixture treatments, doses that did not produce thymic atrophy or cell loss. In addition, RU 486, a glucocorticoid receptor blocker, only partially abrogated the thymic atrophy in mice exposed to the 150/150 mixture of herbicides. These results suggest that glucocorticoids are only partially responsible for herbicide-induced thymic atrophy. This study demonstrates that the effects of exposure to a mixture of chemicals cannot always be predicted based on single exposure data and emphasizes the importance of mixture-based studies.

Energy reserves mobilization in the yellow eel as herbicide exposure effect.

Thiobencarb and propanil are two of the most extensive used herbicides worldwide in rice cultivation. Especially scanty is the available information regarding the effect of herbicides on fish energy resources. In the present study, the effect of sublethal exposure to these herbicides on the energy reserves of juvenile eel Anguilla anguilla was compared. Eels were exposed to 72 h to the herbicide thiobencarb (0.22 mg L(-1)) or Propanil (0.63 mg L(-1)), and allowed to recover in clean water (144 h). Caloric content was determined in liver and skeletal muscle. Fish exposed to thiobencarb rapidly mobilized energy. Reserves from liver were depleted (21%) compared to control values (2.50 kcal g(-1)) at 2 h, whereas in muscle diminished between 12 and 72 h (35%) (control value 0.89 kcal g(-1)). Energy reserves from liver normalized after 144 h in water while in the skeletal muscle were still depleted (24%). Major harmful effects were induced by propanil. Caloric content in liver diminished from the first hours (depletion of 70% at 48h exposure) and in skeletal muscle a 60% (72 h). At the end of the recovery period, energy reserves in pre-exposed eels represented less than 50% compared to control animals. The study indicated that thiobencarb and propanil would constitute a great risk to animals inhabiting freshwater bodies nearby fields of application. Judging from the results, herbicides resulted toxic enough to mobilize fish energy stores. On the other hand, a period of six days in herbicide-free water was not enough time to allow fish to restore energy budgets.

In vitro myelotoxicity of propanil and 3,4-dichloroaniline on murine and human CFU-E/BFU-E progenitors.

Because of the wide use of pesticides for domestic and industrial purposes, the evaluation of their potential effects is of major concern for public health. The myelotoxicity of the herbicide propanil (3,4-dichloroproprioanilide) and its metabolite 3,4-dichloroaniline (DCA) is well documented in mice, but evidence that pesticides may severely compromise hematopoiesis in humans is lacking. In this study, an interspecies comparison of in vitro toxicity of these two compounds on murine and human burst- and colony-forming unit-erythrocyte (BFU-E, CFU-E) and colony-forming unit-granulocyte/macrophage (CFU-GM) progenitors, has been carried out. Murine bone marrow progenitors and human cord blood cells were exposed to propanil or DCA in doses ranging from 10 micro M to 1000 micro M, and the toxic effect was detected by a clonogenic assay with continuous exposure to the compounds. The results on murine cells indicate that the erythrocytic lineage is the most sensitive target for propanil and DCA. On the other hand, human progenitors seem to be less sensitive to the toxic effects of both compounds than murine progenitors at the same concentrations (IC(50) values are 305.2 +/- 22.6 micro M [total erythroid colonies] and >500 micro M [CFU-GM] for propanil). Propanil was significantly more toxic to human erythroid progenitors than to human CFU-GM progenitors, as was found for the murine cells, emphasizing the role of the heme pathway as the target for propanil. These data confirm the evidence that the compounds investigated interfere with erythroid colony formation at different stages of the differentiation pathway and have different effects according to the dose.

Modeling and predicting selected immunological effects of a chemical stressor (3,4-dichloropropionanilide) using the area under the corticosterone concentration versus time curve.

Many chemicals and drugs can induce a neuroendocrine stress response that can be immunosuppressive. Mathematical models have been developed that allow prediction of the immunological impact of such stress responses in mice on the basis of exposure to the important stress-related mediator corticosterone. The area under the corticosterone concentration vs. time curve (AUC) has been used as an indicator of cumulative corticosterone exposure in these modeling studies. In the present study, an immunotoxicant known to induce a stress response, 3,4-dichloropropionanilide (propanil), was evaluated to determine if corticosterone AUC values are related to suppression of immunological parameters in mice treated with this chemical. Linear relationships between corticosterone AUC values and suppression of the following parameters were noted in B6C3F1 female mice: thymus cellularity and thymus subpopulation percentages, splenic subpopulation percentages, natural killer cell activity, MHC class II protein expression, and IgG1 and IgG2a antibody responses to antigen. Linear models derived in previous studies using mice treated with exogenous corticosterone or with restraint stress effectively predicted the immunological effects of 3, 4-dichloropropionanilide on the basis of corticosterone AUC values. The models derived using immobilization stress were more effective (r(2) for observed vs. predicted = 0.90) than the models derived using mice treated with exogenous corticosterone (r(2) for observed vs. predicted = 0.65). This was expected, because most stressors induce a variety of immunomodulatory mediators, not just corticosterone. These findings have implications for risk assessment in immunotoxicology.

Use of the Drosophila wing spot test in the genotoxicity testing of different herbicides.

Four herbicides, namely propanil, maleic hydrazide, glyphosate, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. The herbicides were administered by chronic feeding to 3-day-old larvae. Two different crosses, a standard (ST) and a high-bioactivation (HB) cross, involving the flare-3 (flr(3)) and the multiple wing hairs (mwh) markers, were used. The HB cross uses flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits a more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, which are inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. Maleic hydrazide and glyphosate proved to be more genotoxic in the ST cross, whereas propanil appeared to be slightly more genotoxic in the HB cross. On the other hand, the herbicide 2,4,5-T increased the mutation frequency for only the small single spots in the ST cross.