In 1970, Japanese scholars studied the phase diagram of iron oxide microcrystalline formation, which laid a theoretical foundation for the preparation method of iron oxide yellow crystal seed. According to the research results, iron yellow crystal seeds can be formed under acidic or alkaline conditions. Because iron yellow is a crystal structure, in order to crystallize into pigment particles, it must first form crystal nucleus and become crystal seed, and then the crystal nucleus grows into iron yellow. Otherwise, only thin and dim color paste can be obtained, which does not have pigment properties. Acid process can be divided into iron sheet process and drop addition process.

Mexican researchers sought to evaluate the effects of E171 across a span of conditions in mice, including its influence on behavior, along with the effects on the colon and liver. The research, published in 2020 in the journal Food and Chemical Toxicology, showed that E171 promoted anxiety and induced adenomas, or noncancerous tumors, in the colon. They also found that E171 heightened goblet cells hypertrophy and hyperplasia, which is typically seen in asthma patients and triggered by smoking or external pollutants and toxins. They also noted mucins overexpression in the mice, which can be linked to cancer cell formation.