Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats

Environ Health Perspect. 2007 Sep;115(9):1293-7. doi: 10.1289/ehp.10271.


Background: In a previous study conducted at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation (CMCRC/ERF), we demonstrated for the first time that aspartame (APM) is a multipotent carcinogenic agent when various doses are administered with feed to Sprague-Dawley rats from 8 weeks of age throughout the life span.

Objective: The aim of this second study is to better quantify the carcinogenic risk of APM, beginning treatment during fetal life.

Methods: We studied groups of 70-95 male and female Sprague-Dawley rats administered APM (2,000, 400, or 0 ppm) with feed from the 12th day of fetal life until natural death.

Results: Our results show a) a significant dose-related increase of malignant tumor-bearing animals in males (p < 0.01), particularly in the group treated with 2,000 ppm APM (p < 0.01); b) a significant increase in incidence of lymphomas/leukemias in males treated with 2,000 ppm (p < 0.05) and a significant dose-related increase in incidence of lymphomas/leukemias in females (p < 0.01), particularly in the 2,000-ppm group (p < 0.01); and c) a significant dose-related increase in incidence of mammary cancer in females (p < 0.05), particularly in the 2,000-ppm group (p < 0.05).

Conclusions: The results of this carcinogenicity bioassay confirm and reinforce the first experimental demonstration of APM's multipotential carcinogenicity at a dose level close to the acceptable daily intake for humans. Furthermore, the study demonstrates that when life-span exposure to APM begins during fetal life, its carcinogenic effects are increased.

Keywords: Sprague-Dawley; artificial sweeteners; aspartame; carcinogenicity; lymphomas/leukemias; mammary cancers; prenatal exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartame / toxicity*
  • Carcinogens / toxicity*
  • Carcinoma / chemically induced
  • Female
  • Leukemia / chemically induced
  • Lymphoma / chemically induced
  • Male
  • Neoplasms / chemically induced*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Sweetening Agents / toxicity*
  • Toxicity Tests, Chronic


  • Carcinogens
  • Sweetening Agents
  • Aspartame