Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Several animal and human studies indicate that propyl gallate has a high skin sensitising potential.

In a study by Basketter and Scholes (1992), propyl gallate was tested positive in both the murine local lymph node assay and guinea pig maximisation test. Other literature also supports 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 sensitising 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 sensitising 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.

Human data (see IUCLID sections 7.10.4) on propyl gallate also provide evidence to indicate skin sensitising potential after exposure. Perez et al. (2008) reported 55 cases of allergic contact dermatitis to propyl gallate out of 9529 patients (0.57%) 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 to selected auxiliary substances including propyl gallate. Propyl gallate was one of the most frequently sensitising antioxidising agents, inducing contact hypersensitivity in 0.6% of the patients.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
no guideline followed
GLP compliance:
no
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:

In the EFSA publication "Scientific Opinion on the re-evaluation of propyl gallate (E310) as a food additive", 2014 information on sensitizing potential of propyl gallate based on several studies is presented.

The Scientific Committee on Food stated in its evaluation in 198 that “Gallates may cause skin sensitisation and subsequent exacerbation of the resulting contact dermatitis occurs in some such sensitized individuals after ingestion of gallates.” (SCF, 1989).

Several publications have been reported that propyl gallate has a high sensitising potential and cases of allergic contact dermatitis to propyl gallate, such as cheilitis and dermatitis of the hands (Kraus et al., 1990; Garcia-Melgares et al., 2007; Perez et al., 2008). Furthermore, in a murine local lymph node assay, propyl gallate (dose not specified) was tested positive.

he most common sensitising agent in the case of cosmetics is lipstick and, in an occupational setting, are bakery products. Due to this potential, it has been recommended to limit its concentration in cosmetics (Cosmetic Ingredient Review Expert Panel, 2007). However, the frequency of allergic contact dermatitis appears to be low. Previous exposure and orally induced tolerance, may explained the low rates of allergic contact dermatitis to propyl gallate (Kahn, 1974).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Species:
guinea pig
Interpretation of results:
study cannot be used for classification
Conclusions:
In a publication from Kahn et al. (1974) information on skin sensitisation of propyl gallate is provided. It is described that experiments in guinea pigs showed that propyl gallate has a contact sensitisation potential comparable to that of dinitrochlorobenzene and caused contact dermatitis in five of ten people who applied it for about 20 days. However, no reports of contact sensitisation in the United States has been found. The authors proposed, that induced immunological unresponsiveness (tolerance) is responsible for this lack of overt clinical illness. An experimental model of tolerance has been established to support this hypothesis, in that they have induced specific unresponsiveness by feeding propyl gallate to sensitised guinea pigs.
Executive summary:

In a publication from Kahn et al. (1974) information on skin sensitisation of propyl gallate is provided. It is described that experiments in guinea pigs showed that propyl gallate has a contact sensitisation potential comparable to that of dinitrochlorobenzene and caused contact dermatitis in five of ten people who applied it for about 20 days. However, no reports of contact sensitisation in the United States has been found. The authors proposed, that induced immunological unresponsiveness (tolerance) is responsible for this lack of overt clinical illness. An experimental model of tolerance has been established to support this hypothesis, in that they have induced specific unresponsiveness by feeding propyl gallate to sensitised 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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
no
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich Chemical Co. (Gillingham, Dorset, UK)
Species:
mouse
Strain:
CBA/Ca
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-12 weeks
- Animals of both sexes were used, but single experiments were limited to one sex.
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5%, 10%, 25%
No. of animals per dose:
4
Details on study design:
MAIN STUDY
Groups of 4 mice were treated by a daily topical application of 25 µL of each concentration on the dorsal surface of each ear for 3 consecutive days. Control mice were treated with the vehicle alone. Five days after the first topical application, all mice were injected intravenously through the tail vein with 250 µL phosphate buffered saline (PBS) containing [3H]methyl thymidine (3HTdR; 20 µCi). After 5 hr the mice were killed by carbon dioxide asphyxiation, and the draining auricular lymph nodes were excised and pooled for each experimental group. A single-cell suspension of lymph node cells (LNC) was prepared by gentle mechanical disaggregation through a stainless-steel gauze (200-mesh size), using the plunger of a syringe. Pooled LNC were pelleted at 190g for 10 min, washed twice with 10 mL PBS and resuspended in 3 mL trichloroacetic acid (TCA; 5%) for the precipitation of macromolecules. After an overnight incubation with TCA at 4 °C, the precipitate was recovered by centrifugation, resuspended in 1 mL TCA and transferred to 10mL scintillation fluid. 3HTdR incorporation was measured by beta-scintillation counting. The proliferative response of LNC was expressed as radioactive disintegrations per min per lymph node (dpm/node), and as the ratio of 3HTdR incorporation into LNC of test nodes relative to that recorded for control nodes (test/control ratio).

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay
- Criteria used to consider a positive response: A chemical was regarded as a sensitiser in the LLNA if at least one concentration of the chemical resulted in a three-fold or greater increase in 3HTdR incorporation compared with control values. Also, the data had to be compatible with a biological dose response although an allowance was made, especially at high doses, for either local toxicity or immunological suppression.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
eugenol (CAS No 97-53-0)
mercaptobenzothiazole (CAS No 149-30-4)
Statistics:
N/A
Positive control results:
Cinnamic aldehyde, eugenol and mercaptobenzothiazole were all classified as positive in this assay.
Key result
Parameter:
SI
Value:
>= 22.3
Test group / Remarks:
Concentration of 5%
Key result
Parameter:
SI
Value:
>= 18.3
Test group / Remarks:
Concentration of 10%
Key result
Parameter:
SI
Value:
>= 33.6
Test group / Remarks:
Concentration of 25%
Cellular proliferation data / Observations:
DETAILS ON STIMULATION INDEX CALCULATION : Described in the study as "ratio of test to control lymphocyte proliferation (dpm/node)"
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Using the local lymph node assay technique with [3H]thymidine, propyl gallate at all tested concentrations (5%, 10% and 25%) yielded a positive response (elicited more than a 3-fold increase in isotope incorporation in lymphocytes relative to vehicle controls). Propyl gallate is classified as a skin sensitiser under the conditions of this assay.
Executive summary:

Using the local lymph node assay technique with [3H]thymidine in CBA/Ca mice, propyl gallate at all tested concentrations (5%, 10% and 25%) yielded a positive response (elicited more than a 3-fold increase in isotope incorporation in lymphocytes relative to vehicle controls). Propyl gallate is classified as a skin sensitiser under the conditions of this assay.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Guinea Pig Maximization Test (GPMT)
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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximisation test for 40 chemicals was performed to compare with results of the same chemicals using the local lymph node assay (LLNA).
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich Chemical Co. (Gillingham, Dorset, UK)
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 350 g
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.35%
Day(s)/duration:
A series of six injections in the shoulder region
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25%
Day(s)/duration:
48 hours
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
5%
Day(s)/duration:
24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Not specified
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (induction injection followed by induction patch)
- Exposure period/Frequency of applications/Duration: A series of 6 induction injections (frequency not specified); after 6-8 days, sensitisation was boosted by a 48-hr occluded patch placed over the injection site.
- Test groups: Propyl gallate
- Control group: Not specified
- Site: Shoulder (induction injection and patch)
- Concentrations: 0.35% (injection); 25% (patch)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 h
- Test groups: Propyl gallate
- Control group: Not specified
- Site: Flank
- Concentrations: 5% (maximum non-irritant concentration)
- Evaluation (hr after challenge): Challenge sites were scored for erythema (scale 0-3) and oedema 24 and 48 hr after removal of the patches.

OTHER: Animals were challenged 12-14 days after the induction patch phase.
Challenge controls:
Not specified
Positive control substance(s):
yes
Remarks:
Forty chemicals including some known skin sensitisers were tested in this study.
Key result
Reading:
other: Positive response [%]
Hours after challenge:
48
Group:
test chemical
Dose level:
0.35% induction injection; 25% induction patch; 5% challenge patch
Clinical observations:
Not specified
Remarks on result:
positive indication of skin sensitisation
Remarks:
100% of the tested animals showed positive outcomes; Classified as "extreme" sensitiser
Group:
negative control
Remarks on result:
other: Not specified
Group:
positive control
Remarks on result:
other: Not specified
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Using the guinea pig maximisation test, 100% of the animals exposed to propyl gallate showed positive skin sensitisation potential. Therefore, propyl gallate was classified to be an extreme skin sensitiser under the conditions of this test.
Executive summary:

In this in vivo skin sensitisation test, Albino Dunkin-Hartley guinea-pigs treated by a series of six intradermal injections of the test item propyl gallate (0.35%) in the shoulder region to induce sensitisation. After 6 -8 days, sensitisation was boosted by a 48-hr occluded patch containing 25% of propyl gallate placed over the injection site. 12-14 days later, the animals were challenged on one flank by a 24-hr occluded patch at the maximum non-irritant concentration (5%). Challenge sites were scored for erythema (scale 0-3) and oedema 24 and 48 hr after removal of the patches. 100% of the animals exposed to propyl gallate showed positive skin sensitisation potential. Therefore, propyl gallate was classified to be an extreme skin sensitiser under the conditions of this test.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Several animal and human studies indicate that propyl gallate has a high skin sensitising potential.

In a study by Basketter and Scholes (1992), propyl gallate was tested positive in both the murine local lymph node assay (all 3 tested concentrations eliciting more than 3-fold increase in isotope incorporation in lymphocytes relative to vehicle controls) and guinea pig maximisation test (100% of the tested animals showed positive outcomes by 48h after challenge). In the ‘Scientific Opinion on the re-evaluation of propyl gallate (E 310) as a food additive’, EFSA confirmed the high sensitising potential of propyl gallate, 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 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 55 cases of allergic contact dermatitis to propyl gallate out of 9529 patients (0.57%) 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 to selected auxiliary substances including propyl gallate. Propyl gallate was one of the most frequently sensitising antioxidizing agents, inducing contact hypersensitivity in 0.6% of the patients.

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).