Study of combined multiple exposure and reproductive / developmental toxicity of 2-ethylhexanoic acid by screening method

Introduction. According to the normative and methodological documents of the Russian Federation, chemicals introduced into economic activities are subject to mandatory toxicological assessment and hygienic regulation. To substantiate the value of the hygienic standard of 2-ethylhexanoic acid, the production of which is planned in the country, additional test on its reproductive toxicity was required.

The aim of the research was to determine the no-observed adverse effect levels of the 2-ethylhexanoic acid for maternal and reproductive toxicities in combined multiple exposure and the reproduction/developmental toxicity screening test (OECD 422).

Materials and methods. The study was performed in accordance with the requirements of the OECD Test Guideline 422 «Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test».

Results. During the experiment no animal deaths or clinical symptoms of the toxic effect of 2-ethylhexanoic acid were observed at all tested doses (250, 500 and 1000 mg/kg b.w.). The assessment of behavioural responses using the open field method showed no differences in animals from experimental and control group. Histological examination indicated the acid at doses of 500 and 1000 mg/kg b.w. to cause significant changes in bladder (increased sclerosis in the submucosa), lungs (increased proportion of emphysematous altered parenchyma), adrenal gland (increased cell alterations and lipomatous inclusions), thyroid gland (increased loci of interfollicular tissue) in males and females’ rats. The total weight of offspring in the experimental groups was found to be statistically dose-dependent reduced on days 4 and 13 after birth compared with the control.

Limitations. The study had no limitations.

Conclusion. 2-Ethylhexanoic acid has no effect on the reproductive function in experimental animals. Developmental toxicity, expressed in a decrease in the total weight of offspring, was observed at the level of general toxic effects and is not specific. NOAELs were established at the level of 250 mg/kg b.w. for general toxic effect, > 1000 mg/kg b.w. for reprotoxic effect.

Compliance with ethical standards. The study was approved by the bioethical commission of the Federal Scientific Center of Hygiene named after F.F. Erisman.

Contribution:
Khamidulina Kh.Kh. — concept and design of the study, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Tarasova E.V. — concept and design of the study, collection and processing of materials, text writing, editing;
Zamkova I.V. — text writing, editing;
Masaltsev G.V. — experimental work, collection and processing of materials, writing text.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study was financially supported by Sibur-Khimprom JSC.

Received: May 29, 2024 / Accepted: September 23, 2024 / Published: October 16, 2024