Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1st, 1989 - August 15th, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to ECVAM ToxRTool reliability 1. GLP study performed according to OECD Guideline No 404, "Acute dermal Irritation/Corrosion", 1981

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981's version
Deviations:
yes
Remarks:
extended to investigate 5 different concentrations of the test article and a vehicle control on each animal
GLP compliance:
yes (incl. QA statement)
Remarks:
(16-08-1989)

Test material

Constituent 1
Reference substance name:
HR 89/620001
IUPAC Name:
HR 89/620001
Constituent 2
Chemical structure
Reference substance name:
L-menthol
EC Number:
218-690-9
EC Name:
L-menthol
Cas Number:
2216-51-5
Molecular formula:
C10H20O
IUPAC Name:
2-isopropyl-5-methylcyclohexanol
Constituent 3
Reference substance name:
Cyclohexanol, 5-methyl-2 [1 methylethyl (1R-1α,2β, 5α)]
IUPAC Name:
Cyclohexanol, 5-methyl-2 [1 methylethyl (1R-1α,2β, 5α)]
Details on test material:
- Name of test material (as cited in study report): L-menthol, H&R 89/620001
- Physical state: white crystalline powder (tiny crystals)

Test animals

Species:
rabbit
Strain:
other: Chbb:HM, C.H Boehringer/Biberach:Himalaya strain
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- SPF albino female rabbits
- Source: Chbb:HM, C.H.Boehringer/Biberach:Himalaya strain from Dr Karl Thomae GmbH, D-7950 Biberach an der Riss 1
- Weight at study initiation: between 2400 and 3000 g
- Housing: single PPL cages, 45 x 55 cm, with perforated floor
- Diet (e.g. ad libitum): ad libitum, pellets "Altromin 2123"
- Water (e.g. ad libitum): ad libitum fresh water
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 55 +/- 15%
- Air changes (per hr): 6 time an hour
- Photoperiod (hrs dark / hrs light): from 6 to 18 hours

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: Diethyl phthalate (DEP)
Controls:
other: each animal was concurrently tested with a vehicle control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%, 50%, 25%, 5% and 1% (w/w) of test material concentrations were tested
and vehicle control (0% test material, 100% DEP)
All 5 concentrations and vehicle control were applied to each rabbit.
Duration of treatment / exposure:
Test material was held in place for 4 hours and then the skin was cleaned with soap and lukewarm water.
Observation period:
First reading took place 30 minutes after removing of substance, and then at 24 hours, 48 hours, 72 hours, on day 7 and on day 14.
Number of animals:
4 rabbits were tested
Details on study design:
TEST SITE
- 6 distinct areas on the trunk of each rabbit was used to apply the different concentrations
- Type of wrap if used: test area was covered with gauze packs, 2.5 x 2.5 cm which were secured with a cross of 1 cm wide adhesive tape and fixed with Scanpor tape, 7.5 cm width, loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with soap and lukewarm water
- Time after start of exposure: after 4 hours exposure

SCORING SYSTEM: see table below

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
test material at 100%
Basis:
mean
Time point:
other: average score over all time points
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: underlying skin intact despite white to white-brown scales
Irritation parameter:
erythema score
Remarks:
test material at 50%
Basis:
mean
Time point:
other: average score over all time points
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 14 days for 2 animals
Remarks on result:
other: scattered scale formation on intact skin on 2 of the animals
Irritation parameter:
erythema score
Remarks:
test material at 25%
Basis:
mean
Time point:
other: average score over all time points
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
test material at 5%
Basis:
mean
Time point:
other: average score over all time points
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Remarks:
test material at 1%
Basis:
mean
Time point:
other: average score over all time points
Score:
0
Max. score:
4
Reversibility:
fully reversible within: half an hour
Irritation parameter:
erythema score
Remarks:
vehicle control
Basis:
mean
Time point:
other: average score over all time points
Score:
0
Max. score:
4
Reversibility:
fully reversible within: half an hour
Irritation parameter:
edema score
Remarks:
test material at 100%
Basis:
mean
Time point:
other: average score over all time points
Score:
2.9
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: underlying skin intact despite white to white-brown scales
Irritation parameter:
edema score
Remarks:
test material at 50%
Basis:
mean
Time point:
other: average score over all time points
Score:
2.2
Max. score:
4
Reversibility:
fully reversible within: 14 days for 2 animals
Remarks on result:
other: scattered scale formation on intact skin on 2 of the animals
Irritation parameter:
edema score
Remarks:
test material at 25%
Basis:
mean
Time point:
other: average score over all time points
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Remarks:
test material at 5%
Basis:
mean
Time point:
other: average score over all time points
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Remarks:
test material at 1%
Basis:
mean
Time point:
other: average score over all time points
Score:
0
Max. score:
4
Reversibility:
fully reversible within: half an hour

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information equal to or above 50% Criteria used for interpretation of results: EU
Conclusions:
The test article "HR 891620001" (100%) and "HR 89/620001" equal and above a 50% concentration shall be classified as skin irritant, whereas "HR 89/620001" in concentrations of 25%, 5% and 1% shall not be classified as skin irritant.
Executive summary:

The primary skin irritant effect of "HR/620001" was investigated according to the method recommended in the OECD Guideline No. 404, "Acute Dermal Irritation/Corrosion", 1981. The study design was extended to investigate 5 different concentrations of the test article and a vehicle control on each animal.

Under the experimental conditions described in the authorized report, the mean scores for erythema in the four rabbits were as follows :

test substance concentration

100%

50%

25%

5%

1%

Vehicle

Erythema

3,0

1,6

1,0

0,3

0,0

0,0

Oedema

2,9

2,2

0,2

0,1

0,0

0,0

 

According to the Official Journal of the European Communities, L 257, 1983, the test article "HR 891620001" (100%) and "HR 89/620001" equal to or above 50% concentration shall be classified as skin irritant, whereas "HR 89/620001" in concentrations of 25%, 5% and 1% shall not be classified as skin irritant.