Developmental exposure to a glyphosate- based herbicide increase the risk of neoplastic lesions in uterus and vagina of aged rats

GUERRERO SCHIMPF M; MILESI MM; GASTIAZORO MP; LUQUE EH; VARAYOUD J

Congreso; TOXILATIN 2018; 2018

Introduction: Glyphosate-based herbicides (GBHs) have been one of the most intensive herbicide used over the last two decades. In the last years, it has been controversy regarding its carcinogenic potential. While the European Food Safety Authority concluded ?no evidence of carcinogenicity was confirmed in either rats or mice?, the International Agency for Research on Cancer found there is ?sufficient evidence of carcinogenicity in animals?. Thus, the carcinogenic potential of glyphosate and GBHs in laboratory animals remains uncertain. Estrogens have been implicated as an important etiologic agents in cancer of the female reproductive system. An increased serum 17β-estradiol (E2) to progesterone (P4) ratio has been demonstrated as a mechanism of carcinogenesis in estrogen-dependent tissues.Objective: Investigate whether a brief postnatal exposure to GBH disrupts estrous cyclicity and hormone steroid levels in and causes gynecologic neoplastic lesions in aged rats.Methodology: Female Wistar pups were injected subcutaneously with saline solution (control, C) or GBH using the reference dose (2 mg/kg/day, EPA) on postnatal days (PND) 1, 3, 5, and 7. Animals were left with feed and water ad libitum without further treatment and then the estrous cycle was monitored by vaginal smears (PND120). In addition, blood from the tail was obtained during the estrous stage to determine E2 and P4 serum levels by RIA and ELISA, respectively. Finally, the animals were sacrificed at 20 months of age, the uteri and vagina were dissected and processed for histopathology.Results: GBH-exposed rats showed alterations in estrous cyclicity associated with changes in E2 and P4 serum levels. an An increased level of E2 (C: 28.94±1.36 vsGBH: 33.46±1.03 pg/ml, p