Dipotassium hydrogen citrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

existing human data and experience

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Final Report - On the Safety Assessment of Citric Acid, Inorganic Citrate Salts, and Alkyl Citrate Esters as Used in Cosmetics

Author:

The 2012 Cosmetic Ingredient Review Expert Panel

Year:

2012

Bibliographic source:

Cosmetic Ingredient Review, 1101 17th Street, NW, Suite 412, Washington, DC, 20036-4702

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2007

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Human Repeat Insult Patch Test (HRIPT)

GLP compliance:

no

Type of study:

patch test

Justification for non-LLNA method:

Human data are available from a human patch test. Thus no LLNA test is necessary.

Test material

Test material information

Constituent 1

Reference substance name:

Citric acid

EC Number:

201-069-1

EC Name:

Citric acid

Cas Number:

77-92-9

Molecular formula:

C6H8O7

IUPAC Name:

citric acid

In vivo test system

Test animals

Species:

other: human

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, semiocclusive

Vehicle:

other: cuticle cream

Concentration / amount:

4%

Day(s)/duration:

21 d

Adequacy of induction:

not specified

Details on study design:

HRIPT; semi-occlusive patches applied 3x/wk for 3 wks; a challenge patch was applied after 2 wks.

Results and discussion

In vivo (non-LLNA)

Results

Key result

Reading:

1st reading

Group:

test chemical

Dose level:

4%

No. with + reactions:

0

Total no. in group:

56

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on several studies on citric salts and organic citrate derivatives the CIR Expert Panel concludes the following:
Alkyl derivatives of citric acid might have sensitising properties as the study results are ambigous.
Metal citrates do only have to be considered to be sensitising if caused my the metal moiety of the substance. As alkali metal ions are nonb as non sensitising, those metal salt containing only sodium, potassium and hydrogen can be stated as not sensitising.

Executive summary:

The assessment report states regarding citric salts and compounds:

In sensitization testing, a cuticle cream containing 4% citric acid was not an irritant or a sensitizer in humans.

2.5% aq. citric acid produced positive results in skin prick test in 3 of 91 urticaria or anigoedema patients.

Triethyl citrate, applied undiluted during epidermal induction, was a strong sensitizer in a guinea-pig maximization test, but 20% in pet. was not a primary irritant or sensitizer in human studies.

Trioctyldodecyl citrate was a mild sensitizer in a local lymph node assay when applied neat, but the same concentration was not an irritant or sensitizer in human studies.

Tributyl citrate (concentration not stated) was not a sensitizer in animal studies.

In human studies, 25% tristearyl citrate and 100%  triisostearyl citrate were not irritants or sensitizers in repeated insult patch tests.