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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
2021
Reference Type:
other company data
Title:
Unnamed
Year:
2012
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Principles of method if other than guideline:
Method: other: OECD TG 429
0.1, 0.5, 1, 5 and 25%
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Resorcinol
EC Number:
203-585-2
EC Name:
Resorcinol
Cas Number:
108-46-3
Molecular formula:
C6H6O2
IUPAC Name:
resorcinol

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Nulliparous and non pregnant female CBA/J mice were chosen on the basis of previous studies performed in the laboratory in which CBA/J mice showed the best proliferative response. Females were selected since this sex is recommended by the international guidelines. The Breeder was Janvier, Le Genest-Saint-Isle, France. In the main study 28 females were used (seven groups of 4 animals). On the first day of treatment, the animals were 7 to 12 weeks old and the weight variation of the animals minimal (not exceed 20% of the mean weight). Animals were acclimated at least 5 days before study initiation. Animals were assigned by hand procedure and individually numbered on the tail using an indelible marker.

The animal room conditions will be set as follows: Temp: 22 + 2C; relative humidity: 30 to 70%; light/dark cycle: 12h/12h; ventilation: 12 cycles/hr of filtered, non-recycled air. Animals were housed individually in cages with autoclaved sawdust.

Tap water and A04 pelleted diet were available ad libetum. No containments were known to be present in the diet, drinking water or sawdust (bedding) at levels which may be expected to interfere with or prejudice the outcome of the study.

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
0.1, 0.5, 1, 5 and 25%
No. of animals per dose:
28 (Five treated groups of four animals received the test item plus controls)
Details on study design:
As equivocal results were obtained in the first experiment (see additional robust study summary) and in order to determine more precisely the EC3 value, the test item was then tested in a second experiment. 

In the second study:  Five treated groups of four animals receiving the test item Resorcinol (A011) at the chosen concentrations of 0.1, 0.5, 1, 5 and 25%.  According to the solubility assay performed in the CIT/Study No. 26936 AHS, the vehicle used in the study was DMF. During the induction 
phase, the test item, vehicle or reference item was applied over the ears (25 µL per ear) for 3 consecutive days (days 1, 2 and 3). After 2 days of
resting, the proliferation of lymphocytes in the lymph node draining the application site was measured by incorporation of tritiated methyl thymidine (day 6). The obtained values were used to calculate stimulation indices (SI). 

The irritant potential of the test item was assessed in parallel by measurement of ear thickness on days 1, 2, 3 and 6.

Proliferation Assay:  The incorporation of 3H-TdR in the vehicle control group was as specified in acceptance criteria, the quantity of cells obtained in each group was satisfactory, the cellularity was correlated with incorporation of 3H-TdR, the cell viability in each group was higher than 70% and the 
threshold positive value of 3 for the SI was exceeded in the positive control group. The study was therefore considered valid.

Intravenous injection of 3H-TdR and sampling of auricular lymph nodes Lymph node cell proliferative responses were measured as described by Kimber and Dearman (1991). On day 6 of the experiment, all animals of all groups received a single intravenous injection of 250 µL of 0.9% NaCl containing 20 µCi of 3H-TdR (specific activity of 25 Ci/mmol) via the tail vein. Approximately 5 hours later, the animals were killed by cervical dislocation and the auricular lymph nodes were excised. The lymph nodes were pooled for each experimental group.


Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
linear interpolation of the points on the dose response curve immediately above and below the 3-fold threshold (EC3). The equation used for calculation of EC3 was:
EC3 = c + [(3 - d) / (b - d)] x (a - c) Where a = the lowest concentration giving stimulation > 3; b = the actual stimulation index caused by a; c = the highest concentration failing to produce a stimulation index of 3; and d = the actual stimulation index caused by c.

Results and discussion

Positive control results:
Within range.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
1.58
Test group / Remarks:
0.1% test group
Parameter:
SI
Value:
2.87
Test group / Remarks:
0.5% test group
Parameter:
SI
Value:
1.97
Test group / Remarks:
1% test group
Parameter:
SI
Value:
3.51
Test group / Remarks:
5% test group
Parameter:
SI
Value:
5.74
Test group / Remarks:
25% test group
Key result
Parameter:
EC3
Value:
3.67
Test group / Remarks:
The EC3 value was determined by linear interpolation of points on the dose-response curve, immediately above and below the 3-fold threshold. Assuming SI3 is between the concentration 1% and 5%: EC3=1 + [(3-1.97)/(3.51-1.97)] x (5-1) = 3.67

Any other information on results incl. tables

Systemic clinical signs and mortality: Hypoactivity, piloerection and dyspnea were observed on day 3 in 1/4 and 2/4 animals of the treated groups 4 and 5, respectively.  

Local irritation:  No cutaneous reactions and no noteworthy increase in ear thickness were observed in the animals of the treated groups.

Proliferation assay:  The incorporation of 3H-TdR in the vehicle control group was as specified in acceptance criteria, the quantity of cells obtained in each group was satisfactory, the cellularity was correlated with incorporation of 3H-TdR, the cell viability in each group was higher than 70% and the threshold positive value of 3 for the SI was exceeded in the positive control group. The study was therefore considered valid.

A dose-related increase in the stimulation index (except at the concentration of 1%) was noted and the threshold positive value of 3 was exceeded at the concentrations = 5%.


The EC3 value for the test item Resorcinol (A011) calculated on the basis of the results obtained in this experiment was 1.4%.











































Dose              



# of nodes per group



DPM per group



DPM per node



0.1%



8



514.23



64.28



0.5%



8



933.88



116.74



1%



8



639.94



79.99



5%



8



1142.67



142.83



25%



8



1869.67



233.71



 

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Positive. Resorcinol (AO11) is considered a moderate skin sensitizer under the conditions of this study.

Classification: Skin Sens. 1B H317
Executive summary:

A mouse local lymph node assay (LLNA) was conducted in accordance with OECD TG 429 (, 2005a; RL=1).  The first experiment resulted in equivocal findings at concentrations of 0, 2.5, 5, 10, 25 and 50%. There were four animals per treatment group including negative and positive controls.  Lymphoproliferative responses observed in negative control groups fell within historical ranges, while significant lymphoproliferation was observed with α-hexylcinnamaldehydr at 25%, thus validating the sensitivity of the test system.  A dose related increase in the Stimulation Index (SI) was not seen. In the second experiment five treated groups of four animals were administered resorcinol at concentrations of 0.1, 0.5, 1.0, 1.5 and 25%.  Clinical signs included hypoactivity, piloerection and dyspnea on day 3 in 1 of 4 animals in the 5% group and 2 of 4 animals in the 25% group.  There was no effect on body weight and no cutaneous reactions; there were no noteworthy increases in ear thickness.  A dose-related increase in the stimulation index (except at a concentration of 1%) was noted and the threshold positive value of 3 was exceeded at concentrations equal to 5%.  Resorcinol was considered positive in the LLNA and a moderate skin sensitizer under the conditions of this study.