title: Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.
abstract: Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil also acts as an endocrine disruptor.
authors: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, Av. Prof. Dr. Lineu Prestes 580, São Paulo, Brazil. Electronic address: sayuri_udo@yahoo.com.br.
authors: Mariana S B
authors: MS
authors: Udo
authors: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Science, University of São Paulo, Av. Prof. Dr. Lineu Prestes 580, São Paulo, Brazil.
authors: Thaísa M
authors: TM
authors: Sandini
authors: Institute of Psychology, University of São Paulo, Av. Prof. Mello Moraes 1721, São Paulo, Brazil.
authors: Thiago M
authors: TM
authors: Reis
authors: Graduate Program of Environmental and Experimental Pathology, Paulista University, UNIP, Rua Dr. Bacelar 1212, São Paulo, Brazil; Graduate Program Dentistry, Paulista University, UNIP, Rua Dr. Bacelar 1212, São Paulo, Brazil.
authors: Maria Martha
authors: MM
authors: Bernardi
authors: Department of Pathology, Veterinary Medical School, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, São Paulo, Brazil.
authors: Helenice S
authors: HS
authors: Spinosa
mesh_terms: D000818:Animals; D005260:Female; D006128:Growth / Q000187:drug effects; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008425:Maternal Behavior / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011720:Pyrazoles / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*
chemical_list: D007306:Insecticides; D011720:Pyrazoles; C082360:fipronil
keywords: Developmental toxicity; GABA; Phenylpyrazole insecticide; Spatial brain formation