Acute oral and dermal toxicity parameters of a drug based on D-cyphenothrin, pyriproxyfen and piperonyl butoxide in laboratory animals

The purpose of the research is to study acute oral and dermal toxicity parameters of a drug based on D-cyphenothrin, pyriproxyfen and piperonyl butoxide in laboratory animals.
Materials and methods. The study insectoacaricidal drug contains D-cyphenothrin, pyriproxyfen, piperonyl butoxide, hydrogenated castor oil and isopropyl alcohol. The acute toxicity parameters of the drug in 5% solution formulation were studied on 50 white outbred male mice when administered intragastrically, and on 42 outbred male rats when administered orally and on skin. The acute toxicity parameters were calculated using the Litchfield and Wilcoxon method as modified by Z. Rotha, and the drug exposure value on the body was evaluated as per the established classification (GOST 12.1.007). 
Results and discussion. The following toxicological characteristics were obtained: LD50 of the study drug administered orally to the white mice was 2,656 (2,207.8÷3,187.2) mg/kg, and the white rats, 5,063 (4482÷5818.3) mg/kg. The maximum tolerated dose of the drug was 830 mg/kg for the mice, and 2,075 mg/kg for the rats. Based on the obtained LD50 values, the three-component insectoacaricide can be classified as hazard category 3 (moderately hazardous substances) in experiments on mice, and hazard category 4 (marginally hazardous substances) on rats pursuant to the established hygienic classification. At the same time, different species sensitivity to the drug can be observed in mice and rats. LD50 was more than 30,710 mg/kg in the study of dermal toxicity on the white rats, therefore the drug can be classified as hazard category 4.

1. Arisov M. V., Magomedshapiev G. M., Kurochkina K. G., Uspensky A. V., Malakhova E. I., Novik T. S., Koveshnikova E. I. New means for therapeutic and prophylactic treatments against ixodidosis of cattle on livestock farms in the Republic of Dagestan. Rossijskij parazitologicheskij zhurnal = Russian Journal of Parasitology. 2015; 1: 35-40. (In Russ.)

2. Arisov M. V., Indyuhova E. N., Koshkarev E. A., Arisova G. B. Safety assessment of the combined veterinary drug in drop formulation (“spot on”) «Neoterika Protecto 4». Uchenye zapiski Kazanskoj gosudarstvennoj akademii veterinarnoj mediciny im. N. E. Baumana = Scientific notes of the Kazan State Academy of Veterinary Medicine named after N. E. Bauman. 2018; 234 (2): 22-30. (In Russ.)

3. Belenkiy M. L. Quantitative assessment elements of pharmacological effect. Leningrad: Gosmedizdat, 1963; 152. (In Russ.)

4. Devyatiyarova S. B., Arisov M. V. Acute oral toxicity parameters of a combined antiparasitic drug in spray formulation. «Teoriya i praktika bor'by s parazitarnymi boleznyami»: materialy mezhdunarodnoj nauchnoj konferencii = “Theory and practice of parasitic disease control”: materials of the international scientific conference. 2022; 23: 161-166. (In Russ.) https://doi.org/10.31016/978-5-6046256-9-9.2022.23.161-166

5. Eremina O. Yu., Ibragimkhalilova I. V., Lopatina Yu. V. Comparative determination of the duration of residual activity of different chemical group insecticides on the flea imago (Siphonaptera).Sel'skohozyajstvennaya biologiya = Agricultural Biology. 2010; 6: 108-117. (In Russ.)

6. Indyuhova E. N., Arisov M. V. Insectoacaricide activity of 5% D-cyphenothrin Emulsion against argasid ticks and biting lice. Rossijskij parazitologicheskij zhurnal = Russian Journal of Parasitology. 2024; 18 (2): 211–218. (In Russ.) https://doi.org/10.31016/1998-8435-2024-18-2-211-218.

7. Maximov V. I., Arisov M. V., Indyuhova E. N., Lyalina E. E. Correction of homeostatic disruptions in domestic animals infected with ectoparasites with the use of Inspector Spray. Uchenye zapiski Kazanskoj gosudarstvennoj akademii veterinarnoj mediciny im. N. E. Baumana = Scientific notes of the Kazan State Academy of Veterinary Medicine named after N. E. Bauman. 2016; 227 (3): 43-47. (In Russ.)

8. Stepanov A. A., Arisov M. V. Toxicological assessment of insectoacaricidal Insakar against arachnoentomosis of carnivores. Rossijskij parazitologicheskij zhurnal = Russian Journal of Parasitology. 2012; 1: 98-103. (In Russ.)

9. Stepanov V. A., Arisov M. V., Smirnova E. S. Toxicological evaluation and insectoacaricidal efficacy of Rolf Club 3D spray for dogs and Rolf Club 3D spray for cats. Rossijskij parazitologicheskij zhurnal = Russian Journal of Parasitology. 2014; 3: 112-117. (In Russ.)

10. Shahid A., Zaidi S. D., Akbar H., Saeed S. An investigation on some toxic effects of pyriproxyfen in adult male mice. Iranian Journal of Basic Medical Sciences. 2019; 22 (9): 997-1003. https://doi.org/10.22038/ijbms.2019.33825.8051

11. Evans D., Nijhout F., Parens R., Morales A. J., BarYam Y. A possible link between pyriproxyfen and microcephaly. arXiv preprint arXiv:1604.03834. Cambridge: New England Complex Systems Institute, 2016; 1-6.

12. Reregistration Eligibility Decision for Piperonyl Butoxide (PBO) List B Case No. 2525 United States, Environmental Protection Agency. Prevention. Pesticides and toxic substances. (7508C). EPA 738- R-06-005. Citeseer, 2006; 111.

13. Regulation (EU) No 528/2012 concerning the making available on the market and use of biocidal products. Evaluation of active substances. Assessment Report. Cyphenothrin Product-type 18 (insecticides, acaricides and products to control other arthropods). Greece, 2018; 87.

14. Toxicological evaluations. Joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group. Pyriproxyfen. 2016; 21.