Objective
Childhood cancer incidence has increased by about 35% over the past half-century. Epidemiologic studies document dose-related increases in pediatric cancer following prenatal exposure to ionizing radiation. Additional epidemiologic evidence links parental exposure to chemicals during pregnancy, especially solvents, plastic chemicals, and pesticides, with increased incidence of brain tumors and leukemia in children.
Findings from experimental animal studies on the carcinogenic consequences of prenatal and early postnatal exposures are in many cases more comprehensive and persuasive than the epidemiological data currently available. Animal research has shown that exposures to various chemicals during prenatal or neonatal stages can result in increased cancer incidence. The period from early fetal development through prepuberty is especially vulnerable, as this stage involves complex biological processes characterized by rapid cell division, extensive differentiation, and tightly regulated programmed cell death.
Cancers resulting from early-life exposures to hazardous environmental exposures can arise at any point across the life span from infancy to old age. This framework, the Developmental Origins of Health and Disease (DOHaD) concept, is now broadly recognized and serves as a fundamental principle in public health prevention strategies. It applies to a wide range of non-communicable diseases, including obesity, type 2 diabetes, insulin resistance, asthma, cardiovascular disease, behavioral and neurodegenerative disorders, reproductive health issues, and cancer.
Methods
We evaluated findings from experimental carcinogenesis bioassays in rats involving prenatal chemical exposures conducted at the Cesare Maltoni Cancer Research Center of the Ramazzini Institute, beginning with studies of prenatal exposures to vinyl chloride monomer undertaken in the 1970s.   
Results
Carcinogenesis bioassays in which rodents were exposed to hazardous chemicals in the prenatal and neonatal periods and followed across their entire life span to natural death found increases in incidence of multiple benign and malignant tumors and other toxicological lesions. In many instances, prenatal exposures resulted in higher incidence and earlier onset of benign and malignant tumors than postnatal exposures. The chemical agents assessed included benzene, acrylonitrile, aspartame, ethyl alcohol, vinyl chloride and glyphosate. Prenatal exposure was also evaluated in a series of short-term studies on nicotine raising concerns about developmental stage effects.
Conclusions
This investigation shows that carcinogenesis bioassays that include prenatal and neonatal exposures and long-term follow-up are uniquely well suited for comprehensive evaluation of the lifelong carcinogenic potential of chemical agents. They permit examination of the carcinogenic potential of chemical exposures at different life stages. Their findings are consistent with the DOHaD principle.
We recommend the extended use for regulatory purposes of carcinogenesis bioassays that include prenatal and neonatal exposures and life-long follow-up. These studies are more sensitive than studies that expose only young or adult animals and follow animals for only limited time periods. They therefore have high potential to predict human cancer risk. Such studies will be especially important to protect children from the carcinogenic consequences of early-life exposures to toxic chemicals.