Abstract
Pyriproxyfen is used in Brazil to combat epidemics of Dengue Fever, Chikungunya Fever, and Zika virus. This study assessed the effects of pyriproxyfen on reproductive performance, embryo-fetal development, head measurements, and DNA integrity in a preclinical model. Thirty pregnant mice were divided into three groups (n = 10): control (drinking water—0.1 ml/10 g (body weight—b.w., gavage) and treated with pyriproxyfen 0.0002 mg/kg and 0.0021 mg/kg (b.w., gavage) during the gestational period. Analysis of biometric, reproductive performance and embryo-fetal development parameters related to control presented no significant differences, suggesting no maternal or embryo-fetal toxicity. Head measurements showed no differences except an increase in anterior/posterior measurement and glabella/external occipital protuberance. Analysis of DNA integrity showed an increase in micronucleus only at 72 h for the lowest dose group. Thus, we infer that pyriproxyfen is not related to the occurrence of microcephaly, nor does it alter reproductive performance, embryo-fetal development or DNA integrity.
Similar content being viewed by others
References
Albuquerque MFPM, Souza WV, Mendes AD, Lyra TM, Ximenes RA, Araújo TV, Braga C, Miranda-Filho DB, Martelli CM, Rodrigues LC (2016) Pyriproxyfen and the microcephaly epidemic in Brazil - an ecological approach to explore the hypothesis of their association. Mem Inst Oswaldo Cruz 111(12):774–776. https://doi.org/10.1590/0074-02760160291
Barrow MV, Taylor WJ (1969) A rapid method for detecting malformation in rat fetuse. J Morphol 127(3):291–305
Brasil - Orientações técnicas para utilização do larvicida pyriproxyfen (0,5G) no controle de Aedes aegypti (2014). Disponível em: ˂ http://portalarquivos.saude.gov.br/images/pdf/2014/julho/15/Instru%2D%2D%2D%2Des-para-uso-de-pyriproxifen-maio-2014.pdf >Acess 10/01/2019
Damasceno DC, Cristina P, Francisco JR, Volpato GT, Consonni M, Rudge MVC, Kempinas WG (2008) Anomalias congênitas: estudos experimentais. Editora Média, Belo Horizonte
David N, Mauro MO, Gonçalves CA, Pesarini JR, Strapasson RL, Kassuya CA, Stefanello ME, Cunha-Laura AL, Monreal AC, Oliveira RJ (2014) Gochnatia polymorpha ssp. floccosa: bioprospecting of an anti-inflammatory phytotherapy for use during pregnancy. J Ethnopharmacol 154(2):370–379. https://doi.org/10.1016/j.jep.2014.04.005
Dzieciolowska S, Larroque AL, Kranjec EA, Drapeau P, Samarut E (2017) The larvicide pyriproxyfen blamed during the Zika virus outbreak does not cause microcephaly in zebrafish embryos. Sci Rep 7:40067. https://doi.org/10.1038/srep40067
Gonçalves CA, Siqueira JM, Carollo CA, Mauro MO, de Davi N, Cunha-Laura AL, Monreal AC, Castro AH, Fernandes L, Chagas RR, Auharek SA, Oliveira RJ (2013) Gestational exposure to Byrsonima verbascifolia: teratogenicity, mutagenicity and immunomodulation evaluation in female Swiss mice. J Ethnopharmacol 150(3):843–850. https://doi.org/10.1016/j.jep.2013.09.012
Gonçalves CA, Silva NL, Mauro MO, David N, Cunha-Laura AL, Auharek SA, Monreal AC, Vieira MC, Silva DB, Santos FJ, Siqueira JM, Oliveira RJ (2014) Evaluation of mutagenic, teratogenic, and immunomodulatory effects of Annona nutans hydromethanolic fraction on pregnant mice. Genet Mol Res 13(2):4392–4405. https://doi.org/10.4238/2014
Hanseman JK, Hogan MD (1995) Selection of the experimental unit in teratology studies. Teratology. 12(2):165–172
Harris SB, Hardisty JF, Hayes AW, Weber K (2020) Developmental and reproductive toxicity studies of BIA10-2474. Regul Toxicol Pharmacol 111:104543. https://doi.org/10.1016/j.yrtph.2019.104543
Hayashi M, Morita T, Kodama Y, Sofundi T, Ishidate Junior M (1990) The micronucleus assay with mouse peripheral blood reticulocytes using acridine Orange-coated slides. Mutat Res 245(4):245–249
Maharajan K, Muthulakshmi S, Nataraj B, Ramesh M, Kadirvelu K (2018) Toxicity assessment of pyriproxyfen in vertebrate model zebrafish embryos (Danio rerio): a multi biomarker study. Aquat Toxicol 196:132–145. https://doi.org/10.1016/j.aquatox.2018.01.010
Manson JM, Kang YJ (1994) Test methods for assessing female reproductive and developmental toxicology. In: Hayes AW (ed) Principles and methods of toxicology. Raven Press, New York
Manson JM, Zenich H, Costlowr D (1982) Teratology test methods for laboratory animal. In: Hayes AW (ed) Principles and methods of toxicology. Raven Press, New York
Montenegro MA, Guerreiro MM (s.d.). Protocolos em neurologia infantil. Universidade Estadual de Campinas – UNICAMP
Moreira CQ, Faria MJSS, Baroneza JE, Oliveira RJ, Moreira EG (2005) Developmental exposure to fenproporex: reproductive and morphological evaluation. Hum Exp Toxicol 24(8):397–402
OECD (2001) - Guidelines for testing of chemicals section 4: health effects. Test no. 414: prenatal development toxicity study
OECD (2009) - Guidelines for testing of chemicals. Draft proposal for an extended one-generation reproductive toxicity study. No.28
OECD – (2014) Guideline for testing of chemicals. Mammalian erythrocyte Test. Teste n° 474 de 26/09/2014
OECD – (2015) Guideline for testing of chemicals. Reproduction/Developmental Toxicity Screening Test. Teste n° 421 de 28/07/2015
Oliveira RJ, Salles MJ, da Silva AF, Kanno TY, Lourenço AC, Freiria GA, Matiazi HJ, Ribeiro LR, Mantovani MS (2009) Effects of the polysaccharide ß-glucan on clastogenicity and teratogenicity caused by acute exposure to cyclophosphamide in mice. Regul Toxicol Pharmacol 53(3):164–173. https://doi.org/10.1016/j.yrtph.2008.12.007
Oliveira RJ, Mantovani MS, Pesarini JR, Mauro MO, da Silva AF, Souza TR, Ribeiro LR (2015) 6-Dimethylaminopurine and cyclohexamide are mutagenic and alter reproductive performance and intrauterine development in vivo. Genet Mol Res 14(1):834–849. https://doi.org/10.4238/2015
Parens R, Nijhout HF, Morales A, Xavier Costa F, Bar-Yam Y. (2017) A possible link between pyriproxyfen and microcephaly. PLoS Curr. 9. https://doi.org/10.1371/currents.outbreaks.5afb0bfb8cf31d9a4baba7b19b4edbac
REDUAS (2016) Universidade Vermelha de Ambiente e Saúde. RELATÓRIO dos médicos da cidade pulverizada por culturas sobre dengue-zika, microcefalia e pulverização maciça com venenos químicos, 2016. http://reduas.com.ar/report-from-physicians-in-the-crop-sprayed-town-regarding -diga-zika-microcefalia e pulverização maciça com venenos químicos. Acess 14/02/2020)
Saegusa T (1988) SUMILARV - Study of S-31183 by oral administration during the period of fetal organogenesis in rats
Salewski E (1964) Färbemethoden zum makroskopischen nachweis von implantationsstellen am uterus der ratte Naunym-Schmiedeberg. Archiv Exp Pathol Pharmkol 247:367
Staples RE, Schenell VL (1964) Refinements in rapid clearing technic in the KOH-alizarin red method for fetal bone. Stain Technol 39:61–63
Sumitomo (n.d) (not publicly released; as public record obtained free by request from California Department of Pesticide Regulation and from Sumitomo)
Tang BL (2016) Zika virus as a causative agent for primary microencephaly: the evidence so far. Arch Microbiol 198(7):595–601. https://doi.org/10.1007/s00203-016-1268-7
Taylor P (1986) Pratical Teratology. Academic Press, New York
Usta A, Usta CS, Yildiz A, Ozcaglayan R, Dalkiran ES, Savkli A, Taskiran M (2017) Frequency of fetal macrosomia and the associated risk factors in pregnancies without gestational diabetes mellitus. Pan Afr Med J 2:26–62. https://doi.org/10.11604/pamj.2017.26.62.11440
Vani JM, Monreal MTFD, Auharek SA, Cunha-Laura AL, de Arruda EJ, Lima AR, da Silva CM, Antoniolli-Silva ACMB, de Lima DP, Beatriz A, Oliveira RJ (2018a) The mixture of cashew nut shell liquid and castor oil results in an efficient larvicide against Aedes aegypti that does not alter embryo-fetal development, reproductive performance or DNA integrity. PLoS One 13(3):e0193509. https://doi.org/10.1371/journal.pone.0193509a
Vani JM, Schweich LC, Oliveira KRW, Auharek SA, Cunha-Laura AL, Antoniolli-Silva ACMB, Nazario CED, Oliveira RJ (2018b). Evaluation of the effects of the larvicides temephos on reproductive performance, embryofetal development and DNA integrity of pyriproxyfen WHO - Recommended Classification of Pesticides by Hazard. Guidelines to classification 2000-2002. Disponível em: http://www.who.int/ipcs/publications/en/pesticides_hazard.pdf. Acess 10/01/2019
Vieira-Santos, VS, Caixeta ES, Campos Júnior EOD, Pereira BB (2017) Ecotoxicological effects of larvicide used in the control of Aedes aegypti on nontarget organisms: redefining the use of pyriproxyfen. J Toxicol Environ Health A 80(3):155–160
Vitolo MR (2008) Especificidades dos Nutrientes. Nutrição da gestação ao envelhecimento. Editora Rubio, Rio de Janeiro
Wilson JG (1965) Methods for administering agentes and detecting malformations in experimental animals. In: Wilson JG, Waekany J (eds) Teratology: principles snd Thecniques. The University of Chicago Press, Chicago
World Health Organization (2020) The WHO recommended classification of pesticides by hazard and guidelines to classification 2019. World HealthOrganization
Funding
Financial support was provided by the Brazilian Foundation: FUNDECT MS, CNPq, and CAPES.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Responsible Editor: Philippe Garrigues
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Vani, J.M., de Carvalho Schweich-Adami, L., Auharek, S.A. et al. Pyriproxyfen does not cause microcephaly or malformations in a preclinical mammalian model. Environ Sci Pollut Res 28, 4585–4593 (2021). https://doi.org/10.1007/s11356-020-10517-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-020-10517-5