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Risk Assessment of Impairment of Fertility Due to Exposure to Tobacco Constituents Classified as Reprotoxicants

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Estevan, Carmen, Báez-Barroso, Gabriela A., Vilanova, Eugenio, Sogorb, Miguel A.·2025·Toxics
DOI 10.3390/toxics13040234PMC PMC12031035
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Abstract

Background: Epidemiological studies demonstrate that exposure to tobacco causes infertility. A reference cigarette contains up to 47 chemicals above the quantification level, of which acrylamide, benzopyrene, cadmium, ethylene oxide and lead are classified as known (category 1A), presumed (category 1B) or suspected (category 2) human reproductive toxicants due to their effects on fertility and sexual function. Methods: We collected toxicological information on these substances to establish their respective systemic-derived no-effect levels (internal doses predicted not to alter fertility). We also estimated the systemic exposure to these four substances by smokers consuming 20 cigarettes per day. Results: The risks (ratios between exposure and safe dose) were 0.23, 0.06, 0.18, 0.01 and 0.00002 for acrylamide, benzopyrene, cadmium, ethylene oxide and lead, respectively. The combined risk was 0.48. Conclusions: It was concluded that the changes in fertility resulting from the consumption of the substances in tobacco classified as toxic to fertility could not be explained by mechanisms with a toxicity threshold attributable to these five substances. No safe dose could be derived for tobacco use in persons seeking pregnancy; this applied to both active and passive smokers.

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  • Toxic metals such as cadmium and lead in cigarette smoke disrupt seminal zinc homeostasis and elevate oxidative stress, impairing reproductive function.

    “In addition, toxic metals such as cadmium and lead present in cigarette smoke are known to disrupt seminal zinc homeostasis and elevate oxidative stress, further impairing reproductive function (Machado-Neves 2022, Estevan et al. 2025).”

    From Evaluating the effect of smoking and its cessation on semen parameters (2025) · cites this paper as Estevan et al. 2025

    The Results (§3.1; page not provided) identify cadmium and lead in reference cigarette smoke as toxic to fertility. The Discussion (§4.1.3) links cadmium’s reproductive toxicity to oxidative stress and interference with zinc, but does not specifically describe disruption of seminal zinc homeostasis. Its lead discussion (§4.1.5) does not attribute either zinc disruption or oxidative stress to lead. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Estevan, C., Báez-Barroso, G. A., Vilanova, E., & Sogorb, M. A.
Affiliations
Universitat de Miguel Hernández d'Elx (ES)
Corresponding author
Sogorb, Miguel A.
ORCID
Venue
Toxics
Publisher
MDPI AG
Published
2025-03-23
Volume
13
Issue
4
Pages
234
ISSN
2305-6304 (ISSN-L)
DOI
10.3390/toxics13040234
PMC
PMC12031035
OpenAlex
W4408778593
Cited by
4
References
0
Citations by year
2026: 2 · 2025: 2
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Keywords
tobacco constituents, reproductive toxicity, male infertility, acrylamide, benzopyrene, cadmium, ethylene oxide, lead, no-effect level, combined risk assessment, smokers, passive smoking

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