Relationship Between the Dose Administered, Target Tissue Dose, and Toxicity Level After Acute Oral Exposure to Bifenthrin and Tefluthrin in Young Adult Rats

2019 ◽  
Vol 172 (2) ◽  
pp. 225-234
Author(s):  
Mónica Elizabeth Mosquera Ortega ◽  
Alejandro Martín Pato ◽  
Delfina Mercedes Romero ◽  
Carla Solange Sosa Holt ◽  
Gloria Alvarez ◽  
...  

Abstract Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1–9 mg/kg) and bifenthrin (BIF; 0.5–12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1–6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6–7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans.

Toxicology ◽  
2018 ◽  
Vol 409 ◽  
pp. 53-62 ◽  
Author(s):  
Mónica Elizabeth Mosquera Ortega ◽  
Delfina Mercedes Romero ◽  
Alejandro Martín Pato ◽  
Carla Solange Sosa-Holt ◽  
Adriana Ridolfi ◽  
...  

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 561
Author(s):  
Sara Benedé ◽  
Leticia Pérez-Rodríguez ◽  
Mónica Martínez-Blanco ◽  
Elena Molina ◽  
Rosina López-Fandiño

Scope: House dust mite (HDM) induces Th2 responses in lungs and skin, but its effects in the intestine are poorly known. We aimed to study the involvement of HDM in the initial events that would promote sensitization through the oral route and eventually lead to allergy development. Methods and results: BALB/c mice were exposed intragastrically to proteolytically active and inactive HDM, as such, or in combination with egg white (EW), and inflammatory and type 2 responses were evaluated. Oral administration of HDM, by virtue of its proteolytic activity, promoted the expression, in the small intestine, of genes encoding tight junction proteins, proinflammatory and Th2-biasing cytokines, and it caused expansion of group 2 innate immune cells, upregulation of Th2 cytokines, and dendritic cell migration and activation. In lymphoid tissues, its proteolytically inactivated counterpart also exerted an influence on the expression of surface DC molecules involved in interactions with T cells and in Th2 cell differentiation, which was confirmed in in vitro experiments. However, in our experimental setting we did not find evidence for the promotion of sensitization to coadministered EW. Conclusion: Orally administered HDM upregulates tissue damage factors and also acts as an activator of innate immune cells behaving similarly to potent oral Th2 adjuvants.


Toxics ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 79
Author(s):  
Inge Werner ◽  
Anke Schneeweiss ◽  
Helmut Segner ◽  
Marion Junghans

This study assessed the acute and chronic risk of pesticides, singly and as mixtures, for fish using comprehensive chemical data of four monitoring studies conducted in small- and medium-sized streams of Switzerland between 2012 and 2018. Pesticides were ranked based on single substance risk quotients and relative contribution to mixture risk. Concentrations of the pyrethroid insecticides, λ-cyhalothrin, cypermethrin and deltamethrin, and the fungicides, carbendazim and fenpropimorph, posed acute or chronic single substance risks. Risk quotients of eighteen additional pesticides were equal or greater than 0.1, and thirteen of those contributed ≥30% to mixture risk. Relatively few substances dominated the mixture risk in most water samples, with chronic and acute maximum cumulative ratios never exceeding 5 and 7, respectively. A literature review of toxicity data showed that concentrations of several pesticides detected in Swiss streams were sufficient to cause direct sublethal effects on fish in laboratory studies. Based on the results of our study, we conclude that pesticides detected in Swiss streams, especially pyrethroid insecticides, fungicides and pesticide mixtures, pose a risk to fish health and can cause direct sublethal effects at environmental concentrations. Sensitive life stages of species with highly specialized life history traits may be particularly vulnerable; however, the lack of toxicity data for non-model species currently prevents a conclusive assessment across species.


2012 ◽  
Vol 63 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Xiu-Quan Shi ◽  
Wei Yan ◽  
Ke-Yue Wang ◽  
Qi-Yuan Fan ◽  
Yan Zou

We tested the hypothesis that dietary fi bre (DF) has protective effects against manganese (Mn)-induced neurotoxicity. Forty-eight one-month old Sprague-Dawley rats were randomly divided into six groups: control, 16 % DF, Mn (50 mg kg-1 body weight), Mn+ 4 % DF, Mn+ 8 % DF, and Mn+ 16 % DF. After oral administration of Mn (as MnCl2) by intragastric tube during one month, we determined Mn concentrations in the blood, liver, cerebral cortex, and stool and tested neurobehavioral functions. Administration of Mn was associated with increased Mn concentration in the blood, liver, and cerebral cortex and increased Mn excretion in the stool. Aberrations in neurobehavioral performance included increases in escape latency and number of errors and decrease in step-down latency. Irrespective of the applied dose, the addition of DF in forage decreased tissue Mn concentrations and increased Mn excretion rate in the stool by 20 % to 35 %. All neurobehavioral aberrations were also improved. Our fi ndings show that oral exposure to Mn may cause neurobehavioral abnormalities in adult rats that could be effi ciently alleviated by concomitant supplementation of DF in animal feed.


1974 ◽  
Vol 144 (2) ◽  
pp. 281-292 ◽  
Author(s):  
G Galand ◽  
G G Forstner

The 100000g supernatants from 13-day-old suckling-rat intestinal homogenates contained 43.5% of the total intestinal maltase activity, compared with 7.1% in weaned adult rats aged 40 days. The soluble maltase activity was separated on Sepharose 4B into two quantitatively equal fractions at pH6.0, one containing a maltase with a neutral pH optimum and the other a maltase with an acid pH optimum. The neutral maltase was shown to be a maltase–glucoamylase identical with membrane-bound maltase–glucoamylase in molecular weight, heat-sensitivity, substrate specificity, Km for maltose and Ki for Tris. The soluble enzyme was induced by cortisol, but the ratio of the soluble to bound enzyme fell during induction. Solubility of the neutral maltase was not accounted for by the action of endogenous proteinases under the preparative conditions used. It is postulated that the soluble neutral maltase is a membrane-dissociated form of the bound enzyme and that the relationship between these two forms is modulated by cortisol. The acid maltase generally resembled acid maltase of liver, muscle and kidney. It was shown to be a maltase–glucoamylase with optimal activity at pH3.0, and molecular weight of 136000 by density-gradient centrifugation. At pH3.0 its Km for maltose was 1.5mm. It was inhibited by turanose (Ki=7.5mm) and Tris (Ki=5.5mm) but not by p-chloromercuribenzoate or EDTA. Some 55% of its activity was destroyed by heating at 50°C for 10min. The acid maltase closely resembled β-glucuronidase and acid β-galactosidase in its distribution in the intestine, response to tissue homogenization in various media, and decrease in activity with cortisol treatment and weaning, indicating that it was a typical lysosomal enzyme concentrated in the ileum.


2009 ◽  
Vol 30 ◽  
pp. S1-S16 ◽  
Author(s):  
Myra L. Weiner ◽  
Mark Nemec ◽  
Larry Sheets ◽  
Dana Sargent ◽  
Charles Breckenridge

2011 ◽  
Vol 79 (8) ◽  
pp. 3397-3406 ◽  
Author(s):  
Matthew H. Collins ◽  
Julie M. Craft ◽  
Juan M. Bustamante ◽  
Rick L. Tarleton

ABSTRACTTrypanosoma cruziinfects millions of people in Latin America and often leads to the development of Chagas disease.T. cruziinfection can be acquired at or near the bite site of the triatomine vector, butper osinfection is also a well-documented mode of transmission, as evidenced by recent microepidemics of acute Chagas disease attributed to the consumption of parasite-contaminated foods and liquids. It would also be convenient to deliver vaccines forT. cruziby the oral route, particularly live parasite vaccines intended for the immunization of reservoir hosts. For these reasons, we were interested in better understanding immunity toT. cruzifollowing oral infection or oral vaccination, knowing that the route of infection and site of antigen encounter can have substantial effects on the ensuing immune response. Here, we show that the route of infection does not alter the ability ofT. cruzito establish infection in muscle tissue nor does it impair the generation of a robust CD8+T cell response. Importantly, oral vaccination with attenuated parasites provides protection against wild-type (WT)T. cruzichallenge. These results strongly support the development of whole-organism-based vaccines targeting reservoir species as a means to alleviate the burden of Chagas disease in affected regions.


2021 ◽  
pp. 37-41
Author(s):  
K. D. Ermolenko

Parasitic nematodes of the genus Toxocara are socio-economically important zoonotic pathogens. These parasites are usually directly transmitted to the human host through the fecal-oral route and can cause toxocariasis and related complications, including allergic and neurological disorders. Although tens of millions of people are estimated to have been exposed to Toxocara spp. or are infected with them, global epidemiological information on the relationship between seropositivity and toxocariasis is limited. Recent results show that in some countries the impact of toxocariasis on human health is increasing. The purpose of this review was to analyze modern data on the epidemiology, pathogenesis, clinical and laboratory manifestations and therapy of toxocariasis. Material and methods. The analysis of publications in PubMed, EMBASE and Web of Science systems in the period from January 1950 to September 2020, highlighting studies documenting the epidemiological, pathogenetic, clinical and laboratory aspects of toxocariasis. In addition, we analyzed clinical cases of toxocariasis among patients of the departments of the Pediatric Research and Clinical Center for Infectious Diseases. The article discusses the basic information about toxocars, summarizes the key aspects of the pathogenesis, diagnosis and treatment of toxocariasis, its prevalence, and gives recommendations for the prevention and control of this disease.


Sign in / Sign up

Export Citation Format

Share Document