Doepker D, Tyndall K, Lane R, Wikoff D, Thompson C, Harvey S, Schmitt D. 2017. A proposed ADI for nitrate. Poster presented at Society of Toxicology Annual Meeting, March 16, Baltimore, MD.
Based on experiences with infants over 50 years ago and animal studies from the same period, inorganic nitrate has been considered a water pollutant to be reduced and a food additive to be limited. Recent research shows that this anion is produced in the body, is abundant in fruits and vegetables, and may have health benefits. In fact, people who follow governmentrecommended healthy diets ingest more nitrate than recommended limits. Because of the conflicting historical public health, food, and environmental regulations and the newer nutrition science related to nitrate, a review of its safety was conducted and a proposed acceptable daily intake (ADI) developed. The toxicology and epidemiology of nitrate were reviewed, including methemoglobinemia, cancer, teratology and thyroid endpoints. Additionally, the assumptions and risk assessment approaches used previously by the Joint Expert Committee on Food Additives (JECFA) and the US EPA were examined. Finally, we evaluated what is known about dietary intake of nitrate in healthy diets. JECFA set an ADI of 3.7 mg/kg-day in 1975 based on general toxicity from animal studies where the only effect was reduced body weight with no published data, and confirmed it in 2002. The US EPA set a reference dose (RfD) in 1991 of 7.0 mg/kg-day based on case studies of methemoglobinemia in infants. More recent data show that methemoglobinemia is not an endpoint of concern. The International Agency for Research on Cancer (IARC) concluded that there is no concern for cancer with nitrate except under ill-defined conditions for nitrosation. Our independent assessment involved identifying relevant studies, reviewing and scoring for reliability; a two-year rat cancer study was identified as the critical study. Rats were fed 2.5 and 5% sodium nitrate in the diet (dose equivalent of 910 and 1,820 mg nitrate/kg-day), and no carcinogenic effect was observed. Using the lower dose as the NOAEL and a methodology similar to the JECFA ADI, a safe intake was established at 9.1 mg nitrate/kg-day. A panel of qualified independent experts reviewed our findings. The proposed ADI presented in this evaluation reflects the state of the science related to dietary nitrate safety, is adequately protective of human health, and allows for the benefits of dietary nitrate to be realized by the consumer.