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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Key study. Buehler test method similar to described in OECD 406, GLP study. The test substance did not cause dermal sensitization in guinea pigs under the conditions of this study.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 1991 - December 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
Not specified in the test report.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BuckberG Lab Animals, Tomkins Cove, New York.
- Females (if applicable) nulliparous and non-pregnant: Not specified.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: test group: males: 365.5 (SD=21.97) g; females: 345.1 (SD=15.52) g
- Housing: Guinea pigs were housed individually in 1/2" stainless steel wire mesh cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council. Waste material was removed daily. Cages and feeders sanitized every two weeks.
- Diet (e.g. ad libitum): ad libitum. Purina Guinea Pig DietR. Food was checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering.
- Water (e.g. ad libitum): ad libitum (fresh tap water). Water was monitored for contaminants at periodic intervals according to Standard Operating Procedure PH-018.
- Acclimation period: Minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3ºC,
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12-h dark/light cycle
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.3 mL
Day(s)/duration:
3 applications (once per week for 3 weeks) of 6 hours exposure each.
Adequacy of induction:
other: According to a dose range finding study, the test chemical was dosed as received.
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.3 mL
Day(s)/duration:
1 application of 6 hours
Adequacy of challenge:
other: According to a dose range finding study, the test chemical was dosed as received.
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
4 previously unexposed animals were each exposed to 1.0, 10 and 50% of the test article in acetone and as received. The treated sites (left dorsal surface of each animal) were examined after dosing and scored at 24 hours for erythema according to a similar grading scale shown in paragraph 23 of OECD TG 406. No signs of erythema were observed at any treatment site with the exception of slightly patchy erythema in one animal. Therefore, the test article was dosed as received.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 3 x 6 hours
- Test groups: 1
- Control group: 1 negative and 1 positive control groups.
- Site: left dorsal surface
- Frequency of applications: once a week
- Duration: 3 weeks
- Concentrations: 0.3 mL/site

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 6 hours
- Test groups: 1
- Control group: 1 negative and 1 positive control groups.
- Site: test and positive groups: left dorsal surface; negative group: 80% ethanol on the left flank and test article on the right flank.
- Concentrations: 0.3 mL/site
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:
The negative control animals (10 animals) were challenged with 80% ethanol on the left flank and test article on the right flank.
Positive control substance(s):
yes
Remarks:
A concurrent positive control group consisting of 5 animals was treated with (0.3%) 1-chloro-2,4-dinitrobenzene (DNCB) in ethanol (80%).
Positive control results:
No to severe erythema with/without edema was observed in the positive control animals during the induction. A positive response was elicited in the animals challenged with the positive control article. More details are shown in the table below.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 mL
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.3 mL
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3 mL (test chemical on right flank)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3 mL (test chemical on right flank)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3% DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3% DNCB
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
positive indication of skin sensitisation

Table 2: Individual animal scores

      Induction Challenge
    week 1 2 3 5
    Reading (hrs.) 24 48 24 48 24 48 24 48
  Animal no. Sex                    
Et-NENA

3836

 M 0 0 0 0 0 0 0 0
3837 M 0 0 0 0 0 0 0 0
3838 M 0 0 0 0 0 0 0 0
3839 M 0 0 0 0 0 0 0 0
3840 M 0 0 0 0 0 0 0 0
3841 M 0 0 0 0 0 0 0 0
3842 M 0 0 0 0 0 0 0 0
3843 M 0 0 0 0 0 0 0 0
3844 M 0 0 0 0 0 0 0 0
3845 M 0 0 0 0 0 0 0 0
3846 F 0 0 0 0 0 0 0 0
3847 F 0 0 0 0 0 0 0 0
3848 F 0 0 0 0 0 0 0 0
3849 F 0 0 0 0 0 0 0 0
3850 F 0 0 0 0 0 0 0 0
3851 F 0 0 0 0 0 0 0 0
3852 F 0 0 0 0 0 0 0 0
3853 F 0 0 0 0 0 0 0 0
3854 F 0 0 0 0 0 0 0 0
3855 F 0 0 0 0 0 0 0 0
                         
Positive control
(0.3% DNCB)		 3866 M 0 0 + + 1 2 3 2
3867 M 0 0 + + 1 3 3 3
3868 F 0 0 + + 1 1 3 2
3869 F 0 0 1 1 + + 3 3
3870 F 1 1 1 1 3 3 3 3
                  L R L R
Negative control
(80% ethanol)		 3856 M 0 0 0 0 0 0 0 0 0 0
3857 M 0 0 0 0 0 0 0 0 0 0
3858 M 0 0 0 0 0 0 0 0 0 0
3859 M 0 0 0 0 0 0 0 0 0 0
3860 M 0 0 0 0 0 0 0 0 0 0
3861 F 0 0 0 0 0 0 0 0 0 0
3862 F 0 0 0 0 0 0 0 0 0 0
3863 F 0 0 0 0 0 0 0 0 0 0
3864 F 0 0 0 0 0 0 0 0 0 0
3865 F 0 0 0 0 0 0 0 0 0 0

L - Left flank (80% ethanol)

R = Right flank (EtNENA)

Table 3: Incidence and Severity of Responses at Challenge

Study Number Challenge (Naive site)
24 hours 48 hours
Incidence Severity Incidence Severity
Et-NENA 0/20 0.0 0/20 0.0

Negative control-Et-NENA

 0/10 0.0 0/10 0.0

80% ethanol

 0/10 0.0 0/10 0.0

Positive control

 5/5 3.0 5/5 2.6

Table 4. Summary of Body Weights (g)

Test group
Animal Number Sex Initial Final
3836 M 394 691

3837

 M 350 563

3838

 M 366 597

3839

 M 396 708

3840

 M 378 693
3841 M 334 532
3842 M 343 548
3843 M 385 638
3844 M 361 561
3845 M 348 568
x   365.5 609.9
S.D.   21.97 66.92
N   10 10
3846 F 354 543
3847 F 323 478
3848 F 345 500
3849 F 367 473
3850 F 326 594
3851 F 353 551
3852 F 362 513
3853 F 339 525
3854 F 328 470
3855 F 354 566
x   345.1 521.3
S.D.   15.52 42.18
N   10 10

Negative control
Animal Number Sex Initial Final
3856 M 376 637
3857 M 411 699
3858 M 371 607
3859 M 328 533
3860 M 383 624
x   373.8 620.0
S.D.   29.91 59.76
N   5 5
3861 F 382 553
3862 F 318 513
3863 F 352 511
3864 F 363 545
3865 F 345 556
x   352.0 535.6
S.D.   23.59 21.93
N   5 5

Positive control
Animal Number Sex Initial Final
3866 M 349 593
3867 M 346 536
x   347.5 564.5
S.D.   2.12 40.31
N   2 2
3868 F 312 374
3869 F 347 556
3870 F 357 541
x   338.7 490.3
S.D.   23.63 101.03
N   3 3
Interpretation of results:
other: No category (CLP Regulation EC no. 1272/2008)
Conclusions:
The test substance did not cause dermal sensitization in guinea pigs under the conditions of this study.
Executive summary:

The test substance was tested for delayed contact hypersensitivity in the Buehler Assay (GLP study). In a preliminary dose-range-finding study two male and two female Hartley guinea pigs were exposed to 1.0, 10 and 50% of the test material in acetone and as received. Based upon the results of this study, the test article was dosed as received. For the induction first stage, three groups of Hartley guinea pigs received the test article (10 males and 10 females), the positive control 0.3% 1-chloro-2,4-dinitrobenzene (2 males and 3 females) and the negative control 80% ethanol (5 males and 5 females), respectively, by topical application once per week for a total of three six-hour insult periods. Treated sites were examined and scored at 24 and 48 hours for erythema according to grading scale of 0 to 3 similar to that set out in paragraph 23, OECD TG 406. No signs of erythema were observed in the test article-treated or negative control animals. No to severe erythema with/without edema was observed in the positive control animals. 14 days after the last induction exposure, all animals were challenged (6 hours exposure at the same dose) at a previously untested site. A positive response was elicited in the animals treated with the positive control. No responses were observed in any test article-treated animal. No responses were observed in any control animal challenged with 80% Ethanol on the left flank and test article on the right flank. All animals gained weight and survived to study termination. Based upon these observations, it was concluded that the test substance did not cause dermal sensitization in guinea pigs under the conditions of this study.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for skin sensitisation according to CLP Regulation no. 1272/2008.