Prenatal exposure to a mixture of different phthalates increases the risk of mammary carcinogenesis in F1 female offspring

Thiago de Freitas, Joyce R. Zapaterini, Cristiane M. Moreira, Ariana M. de Aquino, Luiz G. Alonso-Costa, Lucas T. Bidinotto, Laura Kass, Jodi A. Flaws, Wellerson R. Scarano, Luis F. Barbisan

Research output: Contribution to journalArticlepeer-review


Phthalates metabolites have been detected in the urine of pregnant and breastfeeding women. Thus, this study evaluated the adverse effects of maternal exposure to a mixture of six phthalates (Pth mix) on the mammary gland development and carcinogenesis in F1 female offspring. Pregnant female Sprague-Dawley rats were exposed daily to vehicle or Pth mix (35.22% diethyl-phthalate, 21.03% di-(2-ethylhexyl)-phthalate, 14.91% dibutyl-phthalate, 15.10% diisononyl-phthalate, 8.61% diisobutyl-phthalate, and 5.13% benzylbutyl-phthalate) by gavage at 20 μg/kg, 200 μg/kg or 200 mg/kg during gestational day 10 (GD 10) to postnatal day 21 (PND 21). After weaning (PND 22), some female offspring were euthanized for mammary gland analyses while other females received a single dose of N-methyl-N-nitrosourea (MNU, 50 mg/kg) or vehicle and then tumor incidence and multiplicity were recorded until PND 180. Maternal Pth mix exposure increased the number of Ki-67 and progesterone receptor-positive epithelial cells in the mammary gland from Pth mix 200 at μg/kg and 200 mg/kg groups. In addition, tumor incidence and mean number were higher only in Pth mix at 200 mg/kg when compared to the vehicle-treated group, and percentage of tumor-free animals was lower in Pth mix at 200 μg/kg and 200 mg/kg groups. The findings indicate that perinatal Pth mixture exposure increased susceptibility to MNU-induced mammary carcinogenesis in adult F1 female offspring.

Original languageEnglish (US)
Article number112519
JournalFood and Chemical Toxicology
Early online dateAug 21 2021
StatePublished - Oct 2021


  • Chemically-induced mammary tumor
  • F1female offspring
  • Mammary gland development and cancer susceptibility
  • Phthalate mixture

ASJC Scopus subject areas

  • Food Science
  • Toxicology


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