The human health impact of MTBE has been extensively studied, with the first tests screening health risk conducted more than 30 years ago. Based on all the available evidence, MTBE has never been classified as toxic or carcinogenic by any regulatory body anywhere in the world. 

The weight of scientific evidence shows that MTBE has a low order of acute and sub-acute toxicity. It is not teratogenic, mutagenic, neurotoxic, nor is it a reproductive toxicant. The WHO International Programme on Chemical Safety (IPCS) says that "based on collective evidence, it appears unlikely that MTBE alone induces adverse acute health effects in the general population under common exposure conditions."

In 1998, the International Agency for Research on Cancer (IARC) concluded that there was no evidence to justify classifying MTBE as a human carcinogen, and rated it as Group 3 - "non-classifiable". Under the IARC system of classification, Group 1 substances are known carcinogens, Group 2A are probable and Group 2B possible human carcinogens. Group 3 includes common products such as caffeine and talcum powder, as well as fluoride, which is added to drinking water to prevent tooth decay. Group 4 contains only one substance, caprolactam, as likely to be non-carcinogenic to humans.

A number of other well-respected organisations have reached a similar conclusion. The US National Toxicology Program does not include MTBE as a material "reasonably anticipated to be a human carcinogen." According to California Proposition 65, MTBE is not considered as a carcinogenic or reproductive hazard. The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) says that MTBE is not carcinogenic according to criteria in the EU Dangerous Substances Directive 67/548/EC.

In November 2000, the European Union "Working Group on the Classification and Labelling of Dangerous Substances" examined the status of MTBE in a meeting of the relevant Competent Authorities of the 15 Member States held in Ispra (Italy). This meeting of experts resulted in the European Union deciding that MTBE will not be classified as a carcinogen, mutagen or reproductive toxin. This decision has been reflected in Directive 2004/73/EC on the 29th Adaptation to Technical Progress of the EU Dangerous Substances Directive.