Citric acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In accordance with Annex XI, Section 1 of REACH, the evidence based on:

(1) The available developmental toxicity studies. A non standard repeat dose study by Wright and Hughes (1976b) where 5% citric acid was administered in the feed to rats and mice did not give rise to any reproductive effects. In addition a study by Bonting (1956) where 1.2% w/w citric acid in feed given daily to male and female rats over a period of 90 weeks did not give rise to any reproductive effects.  Although these studies are not reliable, they help provide supporting evidence that citric acid is not expected to cause reproductive effects. The no adverse effect level (NOAEL) for reproductive toxicity in rats has been reported as 2500 mg/kg/bw/day (Kim et al, 2013 citing Citric acid SIDS initial assessment report (OECD SIDS, 2001);

(2) A long history of human exposure. For example, Citric Acid is naturally present in common fruit and vegetables. It is also added to processed food and beverages. (HERA 2005). In addition, Citric Acid has well established and documented metabolic pathways in humans. (JECFA, 1973; PFA 2010); is sufficient to fulfil the requirements for this endpoint.

References

Kim, H. M., Shim, I. S., Baek, Y. W., Han, H. J., Kim, P. J., & Choi, K. (2013). Investigation of disinfectants for foot-and-mouth disease in the Republic of Korea. Journal of infection and public health, 6(5), 331-338.

OECD SIDS (2001). SIDS Initial Assessment Report for 11th SIAM (Orlando, Fla., January 2001), for CAS 77-92-9, Citric acid.

Wright and Hughes 1976b: The influence of a dietary citric acid supplement on the reproduction and survival time of mice and rats (publication), Nutr. Rep. Int. 13: 563,

JECFA, 1973. Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents. WHO FOOD ADDITIVES SERIES NO. 5. CITRIC ACID AND ITS CALCIUM, POTASSIUM AND SODIUM SALTS. http://www.inchem.org/documents/jecfa/jecmono/v05je24.htm

PFA (Peter Fisk Associates) 2010: Citric acid and Citrate Salts - Metabolism and Toxicity (secondary source), Owner company; Citrics REACH Consortium,

Additional information

Various studies on rats, mice and guinea pigs using a number of different conditions and protocols: prior to mating, during pregnancy and also a two-generation study, were summarised in the OECD report. In some the doses were defined and in others the regimen was ad libitum feeding of a defined concentration of citric acid in the diet, with or without measurement of food uptake. No adverse effects on females or foetuses were reported except slight dental attrition of the females in some of the studies. The NOEL values reported were often meaningless as it was the only dose used, and that gave no adverse effects. In a two-generation reproductive toxicity, it was shown that 5% citric acid in the diet of female mice and rats had no effect on the reproductive performance as measured by pregnancy rate, number of live births, still births and pup survival rate (Wright and Hughes, 1976b).

Citric acid is naturally present in common fruit and vegetables, and as a consequence there is a long history of human exposure. In addition Citric Acid has well established and documented metabolic pathways in humans. (WHO Food Additives, Series 5, 1973). There is no documented human evidence to suggest that citric acid is either a reproductive or developmental toxicant; this is also substantiated by the animal studies that have been conducted.

Citric acid is a permitted EU Food Additive and, according to the JECFA (Joint Expert Committee on Food Additives of the WHO/ FAO), these products may be used without limitation, according to Good Manufacturing Practice (JECFA, summary of evaluations, citric acid, 1973). The US Food and Drug Administration also classifies citric acid as GRAS (Generally Recognized as Safe) food ingredients. (www.accessdata.fda.gov, 1977).

Effects on developmental toxicity

Description of key information

Developmental toxicity/Teratogenicity:

 

In accordance with Annex XI, Section 1 of REACH, the evidence based on:

(1) The available developmental toxicity studies. A study by the Food & Drug Research Laboratories (1973) researched the teratogenic effects of citric acid in mice (NAOEL > 241 mg/kg/d), rats (NAOEL > 295 mg/kg/d), rabbits (NAOEL > 425 mg/kg/d),  and hamsters (NAOEL > 272 mg/kg/d), There were no reported teratogenic effects in any of the species tested;

(2) A long history of human exposure. For example, Citric Acid is naturally present in common fruit and vegetables. It is also added to processed food and beverages. (HERA 2005). In addition, Citric Acid has well established and documented metabolic pathways in humans. (WHO Food Additives, Series 5, 1973);

is sufficient to fulfil the requirements for this endpoint. 

Justification for classification or non-classification

Based on the available supporting data, the long history of safe use in food and cosmetics, and the central role played by citric acid in metabolism, no classification for reproductive and developmental toxicity is required according Regulation (EC) No 1272/2008.