Allergic reactions
A small number of people react to annatto, from hives and swelling to, rarely, anaphylaxis. Some reactions are true immune allergies, probably to traces of seed protein rather than the pigment. A 1978 study found 26% of people with long-term hives reacted to it, but it had no dummy comparison. A 2021 case report confirmed a reaction with a dummy-controlled eating test.
A patient developed hives, swelling and a dangerous drop in blood pressure within 20 minutes of eating annatto dye. Antibodies to seed proteins in the extract were found, pointing to an immune allergy.
1991ObservationalNish WA et al., Annals of Allergy (case report)
In a challenge study of 56 people with long-term hives, 26% reacted to the amount of annatto in 25g of butter. The study was not blinded and had no dummy comparison.
1978ObservationalMikkelsen H et al., cited in JECFA 52nd meeting monograph on annatto extracts
A dummy-controlled eating test confirmed annatto sensitivity in a patient, with hives as the main symptom.
2021ObservationalSadowska B, Sztormowska M, Chelminska M, Annals of Allergy Asthma and Immunology
European reviewers noted that two cases of anaphylaxis from eating annatto had been reported by 2016, and described severe reactions as rare but real.
2016Regulator reviewEFSA ANS Panel, EFSA Journal (safety of annatto extracts E160b)
A DNA question raised in 2016, and a later rat test
In 2016 European reviewers could not rule out DNA damage, because of a lab test result. New tests in living rats, submitted in 2019, found no DNA damage in the liver or stomach at up to 2,000mg per kg of body weight a day.
Reviewers found weak positive signals in a lab DNA test and could not rule out DNA damage at that stage, and asked for a test in living animals.
2016Regulator reviewEFSA ANS Panel, EFSA Journal 14(8):4544
Young children can reach the norbixin limit
Norbixin has a much lower daily limit than bixin. Estimates in 2017 and 2019 found the highest-consuming toddlers in some European countries reached the norbixin limit. The gap between the highest intakes and the limit is narrow.
Reviewers set the norbixin limit at 0.3mg per kg of body weight a day, against 6mg per kg for bixin.
2016Regulator reviewEFSA ANS Panel, EFSA Journal 14(8):4544
For the top 5% of consumers, estimated norbixin intake reached the limit for toddlers and children in maximum-level scenarios in at least one EU country.
2019Regulator reviewEFSA ANS Panel, EFSA Journal 17(3):5626