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Administrative data

Description of key information

A guinea pig maximization test (OECD 406, GLP) was conducted (TH Goldschmidt AG, 1996). 20 Pirbright-Hartley guinea pigs (m/f) were exposed epicutaneous (occlusive) and intradermal during induction phase. An epicutaneous (occlusive) challenge was performed using a solution with 5% active matter. Results revealed a sensitization rate of 20% and 15% at 24 and 48 h post-challenge, respectively.

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:
key study
Study period:
Sep 1996 - Oct 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Jul 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
No justification given.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: TH Goldschmidt AG, Essen, Germany
- Batch No.of test material: 571003
- Active component: 35%
- Physical state: clear, viscous liquid
- Density: approx. 1.00 g/ml

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient
- Stability under test conditions: March 1997

OTHER SPECIFICS:
- Solvent/vehicle: intradermal injection and dermal application: aqua ad iniect.
Species:
guinea pig
Strain:
Pirbright-Hartley
Remarks:
white. Substrain: Hsd/Poc: DH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, 33178 Borchen, Germany
- Date of receipt: August 7, 1996 (range finding); September 18, 1996 (main test)
- Weight at study initiation: male 308 - 349 g, female 295 - 339 g (main test)
- Housing: collective housing up to a maximum of 10 animals per cage
- Diet: ad libitum, Ssniff-G (Ssniff Spezialdiäten GmBh, Soest, Germany)
- Water: ad libitum
- Acclimation period: 35 days (range finding), 8 days (main test)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12 (illumination from 7 am to 7 pm)
- Measurement: twice daily
Route:
intradermal
Vehicle:
water
Concentration / amount:
2.5%
Day(s)/duration:
7 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50%
Day(s)/duration:
48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
5%
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 animals used for the test substance and 10 control animals
Details on study design:
RANGE FINDING TESTS:
A. INTRADERMAL INJECTION
- Concentration: 5%, dilution with aqua ad iniect. and Freund's complete adjuvant (FCA). Since this concentration produced immoderate irritation such as grey-black discoloration, lower concenrations were tested.
- 4 animals were employed and skin reactions were recorded 48 h post application

B. DERMAL APPLICATION
- the test article was used undiluted. Since the maximum concentration was irritating, lower concentrations were tested.
- occlusive bandage was used
- 10 animals were employed and skin reactions were recorded 48 h post application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 epicutaneous
- Exposure period: - (id), 48 hours (epic)
- Test groups: Test subsstance, Test substance + FCA, FCA (id); Test substance (epic.)
- Control group: FCA, water+FCA, water (id); water (epic.)
- Site: shoulder
- Frequency of applications: 0 (id), 7d (epic.)
- Duration: 0-7d
- Concentrations: 2.5% (id), 50% (epic.)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14d
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: left flank test substance, right flank water
- Concentrations: 5%
- Evaluation (hr after challenge): 24, 48 h
Challenge controls:
Control animals were treated with the test substance concurrently with the test groups in the challenge phase.
Positive control substance(s):
no
Remarks:
The reaction to the positive control substance (benzocaine) is tested periodically. The last test was performed in June 1996.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5%
No. with + reactions:
12
Total no. in group:
20
Clinical observations:
Skin reactions were observed
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5%
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
Skin reactions were observed
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
Skin reactions were observed
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
Skin reactions were observed
Remarks on result:
no indication of skin sensitisation

Table 1: Challenge exposure in the test group - results

 

24h

 

Animal

 

Initial

Test

 

Test

 

Final

no.

Sex

BW(g)

article

E Oe

Vehicle

E Oe

article

E Oe

Vehicle

E Oe

BW(g)

  

1

m

321

0

0

0

0

0

0

0

0

489

2

m

343

0

0

0

0

0

0

0

0

580

3

m

349

1

0

0

0

1

0

0

0

543

4

m

316

1

0

0

0

1

0

0

0

490

5

m

317

2

0

0

0

1

0

0

0

517

6

m

320

0

0

0

0

1

0

0

0

532

7

m

326

0

0

0

0

1

0

0

0

476

8

m

329

1

0

0

0

0

0

0

0

516

9

m

308

1

0

0

0

2

0

0

0

484

10

m

322

0

0

0

0

0

0

0

0

489

11

f

303

1

0

0

0

1

0

0

0

441

12

f

337

1

0

0

0

1

0

0

0

518

13

f

295

2

0

0

0

2

0

0

0

411

14

f

323

0

0

0

0

0

0

0

0

459

15

f

314

2

0

0

0

1

0

0

0

468

16

f

326

0

0

0

0

0

0

0

0

485

17

f

322

0

0

0

0

0

0

0

0

480

18

f

313

1

0

0

0

1

0

0

0

446

19

f

318

1

0

0

0

1

0

0

0

436

20

f

305

2

1

0

0

2

1

0

0

430

 

Reaction rate at 24 h: 60%

Sensitization rate at 24 h: 20%

 

Reaction rate at 48 h: 65%

Sensitization rate at 48 h: 15%

Severity index:

test article (leftflank):

mean value (E) 24 h: 0.80

mean value (Oe) 24 h: 0.05

mean value (E) 48 h: 0.80

mean value (Oe) 48 h: 0.05

 

Severity index: vehicle (rightflank):

mean value(E)24 h: 0.00

mean value (Oe) 24 h: 0.00

mean value(E)48 h: 0.00

mean value (Oe) 48 h: 0.00

 

m=male; f=female; BW=body weight; E=erythema; Oe=oedema

Table 2: Challenge exposure in the control group - results

 

Animal no.

 

Initial SexBW(g)

24hTest

article

E Oe

 

Vehicle

E Oe

48hTest

article

E Oe

 

Vehicle

E Oe

 

Final BW(g)

1

m

324

0

0

0

0

0

0

0

0

522

2

m

320

0

0

0

0

0

0

0

0

518

3

m

317

0

0

0

0

0

0

0

0

471

4

m

314

0

0

0

0

0

0

0

0

484

5

m

310

0

0

0

0

0

0

0

0

468

6

f

303

0

0

0

0

0

0

0

0

509

7

f

339

1

0

0

0

1

0

0

0

511

8

f

317

0

0

0

0

0

0

0

0

508

9

f

327

1

0

0

0

1

0

0

0

500

l0

f

315

0

0

0

0

0

0

0

0

525

Table 2.2.: Results belonging to results presented in table 2

Reaction rate at 24 h:

 

Severity index:

test article (leftflank):

20%

Reaction rate at 48 h:

 

Severity index: vehicle (rightflank):

20%

mean value (E) 24 h:

0.20

mean value(E)24 h:

0.00

mean value (Oe) 24 h:

0.00

mean value (Oe) 24 h:

0.00

mean value(E)48 h:

0.20

mean value(E)48 h:

0.00

mean value (Oe) 48 h:

0.00

mean value (Oe) 48 h:

0.00

 

m=male; f=female; BW=bodyweight; E=erythema; Oe=oedema

Interpretation of results:
GHS criteria not met
Conclusions:
According to the maximization scheme of Magnusson and Kligman (1996), the test substance is classified as a mild sensitzier (The sensitization rate at 24 h was 20 % and at 48 h 15 %).
According to GHS, EU criteria the substance has not to be classfied as skin sensitizer.
Executive summary:

The potential skin sensitizing potential of the test substance was assessed in the guinea pig maximization test using 20 test and 10 control animals. Following induction exposure to the test substance or the vehicle, the animals were subjected to two weeks later to a challenge a challenge exposure with the test substance. The treated skin areas were evaluated 24 and 48 hours after the end of the exposure period. According to Magnusson and Kligman (J. Invest. Dermatol. 52, 268 -276, 1969), the test substance is classified as a "mild sensitizer".

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
GLP compliance:
not specified
Type of study:
other: Repeat-insult patch test study
Justification for non-LLNA method:
No justification given
Specific details on test material used for the study:
1% raw material was used which contained 35% to 36.5% of the test substance utilizing a facial wash
Species:
other: human
Sex:
not specified
Details on test animals and environmental conditions:
Age range: from 18 to 65
Number of subjects: 252 empaneled, 199 completed the study
Key result
Reading:
other: erythema
Hours after challenge:
24
Group:
test group
Dose level:
35 -36.5%
No. with + reactions:
30
Total no. in group:
199
Clinical observations:
24+-reaction; 6 with erythema 1

During the induction phase, three subjects scored +/- (faint, minimal erythema). During the challenge phase, 24 subjects scored +/- and 6 subjects scored a 1 (erythema).

Conclusions:
It was concluded that the test material did not induce contact dermal sensitization in human subjects.
Executive summary:

A repeat-insult patch test study was performed using a facial wash (1% raw material which contained 35% to 36.5% of the test substance) (Harrison Research Laboratories, Inc., 1993). Out of the 252 subjects empaneled (age range from 18 to 65), 199 subjects completed the study. During the induction phase, three subjects scored ± (faint, minimal erythema). During the challenge phase, 24 subjects scored ± and 6 subjects scored a 1 (erythema). It was concluded that the test material did not induce contact dermal sensitization in human subjects.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
GLP compliance:
no
Type of study:
other: Repeat-insult patch test
Justification for non-LLNA method:
No justification given
Specific details on test material used for the study:
1% raw material was used which contained 35% to 36.5% of the test substance
Species:
other: human
Sex:
not specified
Details on test animals and environmental conditions:
Number of participants: 215 subjects enrolled, 189 completed the study
Age: from 18 to 70
Route:
epicutaneous, semiocclusive
Vehicle:
not specified
Concentration / amount:
0.2 ml
Day(s)/duration:
24 h
Route:
other: epicutaneous
Vehicle:
not specified
Day(s)/duration:
24 h
Details on study design:
The test material (0.2 ml) was dispensed onto the semiocclusive webril/adhesive patch, and placed on the left side of the back. Each subject removed the patch 24 h later, and the procedure was repeated after a 24-h nonapplication period (48 h on the weekends) for a total of nine induction patches. The test site was observed for any signs of reaction and recorded at the time a new patch was reapplied. The subjects were given a 2-week period of non-treatment, which was followed by the challenge dose. The challenge patch was applied to the right side of the back for 24 h. The site was observed for a reaction immediately after removal and again 48, 72, and 96 h after application.
Key result
Reading:
other: erythema
Hours after challenge:
48
Group:
test group
Dose level:
35-36.5%
No. with + reactions:
1
Total no. in group:
189
Clinical observations:
+

During induction, two ± reactions (faint, minimal erythema) were noted at the first reading. During challenge, only one ± reaction was noted at the 48 h postapplication observation.

Conclusions:
It was concluded that the test substance did not induce dermal sensitization.
Executive summary:

A repeat-insult patch test was conducted using a facial wash (1% raw material containing 35% to 36.5% of the test substance) (Harrison Research Laboratories, Inc., 2001a). Of the 215subjects enrolled, 189 completed the study (ages ranged from 18 to 70). The test material (0.2 ml) was dispensed onto the semiocclusive webril/adhesive patch, and placed on the left side of the back. Each subject removed the patch 24 h later, and the procedure was repeated after a 24-h nonapplication period (48 h on the weekends) for a total of nine induction patches. The test site was observed for any signs of reaction and recorded at the time a new patch was reapplied. During these observations, two ± reactions (faint, minimal erythema) were noted at the first reading.

The subjects were given a 2-week period of non-treatment, which was followed by the challenge dose. The challenge patch was applied to the right side of the back for 24 h. The site was observed for a reaction immediately after removal and again 48, 72, and 96 h after application. During this phase, only one + reaction was noted at the 48-h postapplication observation.

It was concluded that the test substance did not induce dermal sensitization (Harrison Research Laboratories, Inc. 2001a).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
GLP compliance:
not specified
Type of study:
other: Modified Draize assay
Justification for non-LLNA method:
No justification given
Specific details on test material used for the study:
A test product was used which contained 7.5% of the test substance
Species:
other: human
Sex:
not specified
Details on test animals and environmental conditions:
Number of participants: 120 empaneled, and 110 completed the study
Route:
epicutaneous, occlusive
Vehicle:
not specified
Concentration / amount:
0.025 g of the test product
Day(s)/duration:
48/72 h (72 h on weekends)
Route:
other: epicutaneous
Vehicle:
not specified
Concentration / amount:
0.025 g of the test product
Day(s)/duration:
48 h
Details on study design:
Induction: 0.025 g of the test material was applied to the scapular area of the back under occlusive patches. A total of 10 applications were made. 48 h after patch application (72 h on weekends), the patches were removed and the test sites were rinsed and evaluated. New patches were then applied. Twelve days after removal of the last patch, a challenge patch with the same dose used during induction was applied to a previously untested site. The challenge patch was removed 48 h after application, and the site was evaluated 48 and 96 h after application.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
No. with + reactions:
2
Total no. in group:
110
Clinical observations:
1+ reactions
Reading:
2nd reading
Hours after challenge:
96
Group:
test group
No. with + reactions:
2
Total no. in group:
110
Clinical observations:
1+ reactions

During the induction phase of the study, 1+ reactions (erythema throughout the entire patch area) were observed in 53 subjects and 2+ reactions (erythema and edema) were observed in three subjects. These reactions were considered typical of mild irritation. Two of the subjects had 1+ reactions at the 48- and 96 -h challenge readings.

Conclusions:
The researchers concluded that no evidence of sensitization to 7.5% of the test substance was observed.
Executive summary:

A modified Draize assay was performed using a test product containing 7.5% of the test substance (International Research Services, Inc., 1997). Of the original 120 subjects, 110 completed the study. During induction, 0.025 g of the test material was applied to the scapular area of the back under occlusive patches. A total of 10 applications were made. Forty-eight hours after patch application (72 h on weekends), the patches were removed and the test sites were rinsed and evaluated. New patches were then applied. Twelve days after removal of the last patch, a challenge patch with the same dose used during induction was

applied to a previously untested site. The challenge patch was removed 48 h after application, and the site was evaluated 48 and 96 hours after application.

During the induction phase of the study, 1 + reactions (erythema throughout the entire patch area) were observed in 53 subjects and 2+ reactions (erythema and edema) were observed in three subjects. These reactions were considered typical of mild irritation. Two of the subjects had 1+ reactions at the 48—and 96-h challenge readings. The researchers concluded that “no evidence of sensitization” to 7.5% of the test substance was observed (International Research Services, Inc. 1997).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study was performed in order to assess the skin sensitizing potential of the test substance using the guinea pig maximization test which was according to OECD guideline 406 and in compliance with GLP in 1996 (TH Goldschmidt AG, 1996). Twenty test and 10 control Pirbright-Hartley guinea pigs both male and female were exposed epicutaneous (occlusive) and intradermal to a dilution of 50% and 2.5%, respectively, during induction phase. Following induction exposure to the test substance or the vehicle, the animals were subjected two weeks later to an epicutaneous (occlusive) challenge using a solution with 5% active matter. The treated skin areas were evaluated 24 and 48 hours after the end of the exposure period. Results revealed a sensitization rate of 20% and 15% at 24 and 48 h post-challenge, respectively. According to Magnusson and Kligman (J. Invest. Dermatol. 52, 268 -276, 1969), the test substance is classified as a "mild sensitizer". Applying the GHS (UN) criteria, no classification is triggered.

Harrison Research Laboratories, Inc. performed a non-guidelien repeat-insult patch test study with no information on GLP compliance in 1993. A facial wash (1% raw material which contained 35% to 36.5% of the test substance) was used. Out of the 252 subjects empaneled (age range from 18 to 65), 199 subjects completed the study. During the induction phase, three subjects scored ± (faint, minimal erythema). During the challenge phase, 24 subjects scored ± and 6 subjects scored a 1 (erythema). It was concluded that the test material did not induce contact dermal sensitization in human subjects.

International Research Services, Inc. (1997) performed a modified Draize assay using a test product containing 7.5% of the test substance. Of the original 120 subjects, 110 completed the study. During induction, 0.025 g of the test material was applied to the scapular area of the back under occlusive patches. A total of 10 applications were made. Forty-eight hours after patch application (72 h on weekends), the patches were removed and the test sites were rinsed and evaluated. New patches were then applied. Twelve days after removal of the last patch, a challenge patch with the same dose used during induction was applied to a previously untested site. The challenge patch was removed 48 h after application, and the site was evaluated 48 and 96 hours after application.

During the induction phase of the study, 1 + reactions (erythema throughout the entire patch area) were observed in 53 subjects and 2+ reactions (erythema and edema) were observed in three subjects. These reactions were considered typical of mild irritation. Two of the subjects had 1+ reactions at the 48—and 96-h challenge readings. The researchers concluded that “no evidence of sensitization” to 7.5% of the test substance was observed.

Harrison Research Laboratories, Inc. (2001a) conducted a repeat-insult patch test using a facial wash (1% raw material containing 35% to 36.5% of the test substance). Of the 215

subjects enrolled, 189 completed the study (ages ranged from 18 to 70). The test material (0.2 ml) was dispensed onto the semiocclusive webril/adhesive patch, and placed on the left side of the back. Each subject removed the patch 24 h later, and the procedure was repeated after a 24-h nonapplication period (48 h on the weekends) for a total of nine induction patches. The test site was observed for any signs of reaction and recorded at the time a new patch was reapplied. During these observations, two ± reactions (faint, minimal erythema) were noted at the first reading.

The subjects were given a 2-week period of non-treatment, which was followed by the challenge dose. The challenge patch was applied to the right side of the back for 24 h. The site was observed for a reaction immediately after removal and again 48, 72, and 96 h after application. During this phase, only one + reaction was noted at the 48-h postapplication observation.

It was concluded that the test substance did not induce dermal sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008.