Citric acid

Endpoint summary

Description of key information

In a skin sensitisation study with limited details which was not conducted according to a guideline or in compliance with GLP, the test substance citric acid was concluded to not be a skin irritant or a sensitiser when tested to human volunteers (Clinical Research Laboratories, 2007 as cited in Cosmetic Ingredient Review, 2012).

In a skin prick test which was not conducted according to any guideline or in compliance to GLP, it was observed that the test substance, citric acid, caused positive results in 3 out of 91 patients. Very limited details were given in the study source (Malanin & Kalimo, 1989 as cited in Cosmetic Ingredient Review, 2012).

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No published sensitisation studies were identified for citric acid in the literature search.

In accordance with REACH Annex XI Section 2, the sensitisation study (required in Section 8.3) does not need to be conducted because citric acid and its salts have been used for many years as permitted additives for human food, medicines and cosmetics. During this time, there has been no documented evidence that citric acid could be a sensitiser. Therefore, there is no scientific basis for recommending animal studies to investigate this endpoint.

 

There are no structural alerts that suggest citric acid is a sensitiser. Similarly, other acids, e.g. the phosphonates groups, are also not known to be sensitisers.

Information on sensitisation in humans has been reviewed in the OECD SIDS 2001, and the data referenced has been accepted in an international peer review process (SIAM 11, 2001):

 

“Symptoms of possible sensitisation” were described following the ingestion of foods containing citric acid. Challenge by direct application of citric acid crystals to the inside surface of his mouth produced sores; which was also the case with some of the other organic acids that were tested. However potassium citrate crystals and magnesium citrate solution did not elicit a similar response. In another case, urticaria and mouth ulcers were reported following exposure to citric acid, with no further details given.

 

A standard textbook implies that citric acid might be a skin sensitizer by recommending patch tests with aqueous solutions to detect sensitised individuals. However, patch testing of 60 eczema patients with 2.5% citric acid in petrolatum did not produce any irritant or allergic reactions. Genuine sensitisation to citric acid seems to be a rare phenomenon (Niinimaki 1987).

In a skin sensitisation study with limited details which was not conducted according to a guideline or in compliance with GLP, the test substance citric acid was concluded to not be a skin irritant or a sensitiser when tested to human volunteers (Clinical Research Laboratories, 2007 as cited in Cosmetic Ingredient Review, 2012). At induction, patches of 4 % citric acid in a cuticle cream were applied onto the skin of 56 human volunteers, under a semi-occlusive dressing, three times a week for three weeks. At challenge, 4 % citric acid in a cuticle cream was applied dermally to 56 human volunteers two weeks after the last induction (Clinical Research Laboratories, 2007 as cited in Cosmetic Ingredient Review, 2012).

In a skin prick test which was not conducted according to any guideline or in compliance to GLP, it was observed that the test substance, citric acid, caused positive results in 3 out of 91 patients. Very limited details were given in the study source (Malanin & Kalimo, 1989 as cited in Cosmetic Ingredient Review, 2012).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No data are available which suggest that citric acid should be classified as a skin or respiratory sensitiser according to Regulation (EC) No 1272/2008.