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Description of key information

Several studies indicate that propyl gallate has a high sensitising potential.

In a study cited by Kimber (1994), propyl gallate was tested positive in a murine local lymph node assay. Further literature does support the result of this key study. In the ‘Scientific Opinion on the re-evaluation of propyl gallate (E 310) as a food additive’, EFSA confirms the high sensitizing potential of propyl gallate by citing several studies. Kahn et al. (1974) described a contact dermatitis in 5 of 10 people who applied propyl gallate for about 20 days. Furthermore, they conducted separate tests in guinea pigs in order to determine the sensitizing potential of propyl gallate and concluded, based on these studies, that propyl gallate is a strong sensitiser when given intradermally and a less sensitiser when given cutaneous. Perez et al. (2008) reported cases of allergic contact dermatitis to propyl gallate in 9,529 patients from 1988 to 2005. In a study from Dastychova et al. (2004), a group of 514 chronic eczema patients were tested by means of epicutaneous tests for contact hypersensitivity. Of the four antioxidizing agents tests, Propyl gallate 0.6% was the third most frequently sensitizing agent.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2001-2004
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Reference:
Composition 0
Principles of method if other than guideline:
Patients with chronic eczema tested using epicutaneous tests (patch test) for contact hypersenitivity.
GLP compliance:
not specified
Type of study:
patch test
Specific details on test material used for the study:
Propyl gallate in 0.6%
Species:
other: human
Sex:
male/female
Details on test animals and environmental conditions:
Average age: 42.8 years
Route:
other: epicutaneous, method not specified
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
Not specified
Adequacy of induction:
not specified
Details on study design:
514 patients (178 men, 336 women) suffering from chronic eczema were tested by means of epicutaneous tests for contact hypersensitivity to selected substances of dermatological external and cosmetic preparations.
Remarks on result:
not determinable
Interpretation of results:
study cannot be used for classification
Conclusions:
Of the 4 antioxidizing agents, Propyl gallate in 0.6% was the third most frequently sensitizing agent.
Executive summary:

From April 2001 to December 2002, a group of 514 chronic eczema patients were tested by means of epicutaneous tests for contact hypersensitivity. Of the four antioxidizing agents tests, Propyl gallate 0.6% was the third most frequently sensitizing agent.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
other: agency summary
Adequacy of study:
supporting study
Study period:
2014
Reliability:
4 (not assignable)
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
[3H]thymidine
GLP compliance:
no
Species:
mouse
Strain:
not specified
Sex:
not specified
Vehicle:
not specified
Concentration:
Not specified
No. of animals per dose:
Not specified
Positive control results:
Not specified
Test group / Remarks:
Positive
Interpretation of results:
study cannot be used for classification
Conclusions:
EFSA concludes in this review/scientific opinion that propyl gallate has a high sensitising potential and cases of allergic contact dermatitis have been reported (usually cheilitis and dermatitis of the hands). The frequency of allergic contact dermatitis appears to be low, and only very rare reactions have been reported after oral intake of gallates. The use of propyl gallate as a food additive raise concern as regards allergenicity, hypersensiivity and intolerance. This study cites Kimber et al. 1994 which concluded that propyl gallate (unspecified dose) tested positive in a murine local lymph node assay.
Executive summary:

EFSA concludes in this review/scientific opinion that propyl gallate has a high sensitising potential and cases of allergic contact dermatitis have been reported (usually cheilitis and dermatitis of the hands). The frequency of allergic contact dermatitis appears to be low, and only very rare reactions have been reported after oral intake of gallates. The use of propyl gallate as a food additive raise concern as regards allergenicity, hypersensiivity and intolerance. This study cites Kimber et al. 1994 which concluded that propyl gallate (unspecified dose) tested positive in a murine local lymph node assay.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1974
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Reference:
Composition 0
Principles of method if other than guideline:
Patch test: test material directly applied to skin of subjects for 20 days
GLP compliance:
not specified
Type of study:
patch test
Species:
guinea pig
Sex:
not specified
Route:
other: no details
Vehicle:
not specified
Concentration / amount:
Not specified
Day(s)/duration:
20
Adequacy of induction:
not specified
Adequacy of challenge:
not specified
Details on study design:
In humans, test substance was applied to 20 days. In guinea pigs, specific immunological unresponsiveness (tolerance) was induced by feeding propyl gallate to sensitized guinea pigs.
Positive control substance(s):
not specified
Positive control results:
Not specified
Remarks on result:
not determinable
Interpretation of results:
study cannot be used for classification
Conclusions:
Propyl gallate caused contact dermatitis in 5 of 10 people who applied it for about 20 days; the study induced specific unresponsiveness by feeding propyl gallate to sensitized guinea pigs.
Executive summary:

Propyl gallate caused contact dermatitis in 5 of 10 people who applied it for about 20 days; the study induced specific unresponsiveness by feeding propyl gallate to sensitized guinea pigs.

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
no
Type of study:
mouse local lymphnode assay (LLNA)
Test material information:
Composition 1
Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Vehicle:
other: not specified
Concentration:
Not specified
No. of animals per dose:
Not specified
Details on study design:

MAIN STUDY

Mice of CBA/Ca strain receive 3 consecutive daily applications of various concentrations of the test chemical to the dorsum of both ears. Five days following the initiation of exposure both test and control (vehicle-treated) mice are injected intravenously with [3H]thymidine. Animals are sacrificed 5 h later, the draining auricular lymph nodes excised and pooled for each experimental group and a single cell suspension of LNC prepared and processed for/3-scintillation counting. Chemicals are classified as being 'sensitizers' or 'not strong sensitizers' according to the level of [3H]thymidine incorporation recorded.

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
Local lymph node assay
- Criteria used to consider a positive response:
The criterion for a positive response is that one or more concentrations of a test chemical should elicit a 3-fold or greater increase in isotope incorporation relative to vehicle controls. The choice of a stimulation index of 3 as being discriminatory was originally somewhat arbitrary, but has since been largely borne out by experience.

TREATMENT PREPARATION AND ADMINISTRATION: Not specified
Positive control results:
Not specified
Key result
Parameter:
SI
Value:
>= 3
Remarks on result:
not determinable because of methodological limitations
Remarks:
No other information on test result other than "positive"
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Using the local lymph node assay technique with [3H]thymidine, test substance propyl gallate yielded a positive response (one or more concentrations elicited a 3-fold or greater increase in isotope incorporation relative to vehicle controls).
Executive summary:

Using the local lymph node assay technique with [3H]thymidine in CBA/Ca mice, test substance propyl gallate yielded a positive response, defined as one or more concentrations eliciting a 3-fold or greater increase in isotope incorporation relative to vehicle controls.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988-2008
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Reference:
Composition 0
Principles of method if other than guideline:
Patients were patch tested to the face series to assess the prevalence of allergic contact dermatitis.
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
Human subjects used
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel:
1% petrolatium
Species:
other: human
Sex:
male/female
Details on test animals and environmental conditions:
9,529 patients: 6,973 females and 2,556 males
No. of animals per dose:
9,529 patients
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Not specified
- Exposure period: Not specified
- Test groups: Not specified
- Control group: Not specified
- Site: face
- Frequency of applications: Not specified
- Duration: Not specified
- Concentrations: Not specified
Challenge controls:
Not specified
Positive control substance(s):
not specified
Positive control results:
Not specified
Group:
test group
Dose level:
not specified
No. with + reactions:
55
Total no. in group:
9 529

Using chi-square, there was a significant different (p<0.05) in the positivity rates between the 1988 -96 period (0.45% read positive) and the 1997 -2005 period (0.77% read positive).

Interpretation of results:
study cannot be used for classification
Conclusions:
A total of 55 patients had positive reactions to propyl gallate 1% pet. (0.57%), 46 were female (0.65%) and 9 were male (0.33%). Using chi-square, there was a significant difference (P < 0.05) in the positivity rates between the 1988-96 period (0.45%) and the 1997-2005 period (0.77%).There was a statistically significant increase in propyl gallate-positive rates on patch testing over the last decade.
Executive summary:

Using a face series patch test technique, the prevalence of allergic contact dermatitis to the test substance propyl gallate was assessed with 9,529 patients from 1988 to 2005. Positive reactions were scored as per International Contact Dermatitis Research Group recommednations. A total of 55 patients had positive reactions to propyl gallate 1% pet. (0.57%), 46 were female (0.65%) and 9 were male (0.33%). Using chi-square, there was a significant difference (P < 0.05) in the positivity rates between the 1988-96 period (0.45%) and the 1997-2005 period (0.77%).There was a statistically significant increase in propyl gallate-positive rates on patch testing over the last decade.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Several studies indicate that propyl gallate has a high sensitising potential.

In a study cited by Kimber (1994), propyl gallate was tested for skin sensitization potential using the local lymph node assay technique with [3H]thymidine in CBA/Ca mice. The test substance propyl gallate yielded a positive response, defined as one or more concentrations eliciting a 3-fold or greater increase in isotope incorporation relative to vehicle controls.

In the ‘Scientific Opinion on the re-evaluation of propyl gallate (E 310) as a food additive’, EFSA confirm the high sensitizing potential of propyl gallate by citing several studies. In these studies, cases of contact dermatitis have been reported, usually cheilitis and dermatitis of the hands.

Kahn et al. (1974) described a contact dermatitis in 5 of 10 people who applied propyl gallate for about 20 days. Furthermore, they conducted separate tests in guinea pigs in order to determine the sensitizing potential of propyl gallate and concluded, based on these studies, that propyl gallate is a strong sensitiser when given intradermally and a less sensitiser when given cutaneous. Perez et al. (2008) reported cases of allergic contact dermatitis to propyl gallate in 9,529 patients from 1988 to 2005. In a study from Dastychova et al. (2004), a group of 514 chronic eczema patients were tested by means of epicutaneous tests for contact hypersensitivity. Of the four antioxidizing agents tests, propyl gallate 0.6% was the third most frequently sensitizing agent.

Based on the result of the key study as well as the information from public literature it can be concluded that propyl gallate is a skin sensitiser.

Justification for classification or non-classification

Based on the result of the key study as well as the information from public literature it can be concluded that propyl gallate is a skin sensitiser and is considered to be classified for Skin Sensitisation Category 1 (H317).