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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.
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
The received test article was treated for dessication prior to administration in the definitive test.
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: 366.7 (SD=15.72) g; females: 346.4 (SD=13.92) 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:
300 mg moistened with 0.3 mL distilled water.
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 (after dessication).
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
300 mg moistened with 0.3 mL distilled water.
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 (after dessication).
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. 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: 300 mg/site moistened with 0.3 mL distilled water.

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: distilled water on the left flank and test article on the right flank.
- Concentrations: 300 mg/site moistened with 0.3 mL distilled water.
- Evaluation (hr after challenge): 24 and 48 hours

Challenge controls:
The negative control animals (10 animals) were challenged with distilled water 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:
300 mg/site moistened with 0.3 mL distilled water.
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:
300 mg/site moistened with 0.3 mL distilled water.
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:
300 mg/site moistened with 0.3 mL distilled water (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:
300 mg/site moistened with 0.3 mL distilled water (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                    
Me-NENA 3801 M 0 0 0 0 0 0 0 0
3802 M 0 0 0 0 0 0 0 0
3803 M 0 0 0 0 0 0 0 0
3804 M 0 0 0 0 0 0 0 0
3805 M 0 0 0 0 0 0 0 0
3806 M 0 0 0 0 0 0 0 0
3807 M 0 0 0 0 0 0 0 0
3808 M 0 0 0 0 0 0 0 0
3809 M 0 0 0 0 0 0 0 0
3810 M 0 0 0 0 0 0 0 0
3811 F 0 0 0 0 0 0 0 0
3812 F 0 0 0 0 0 0 0 0
3813 F 0 0 0 0 0 0 0 0
3814 F 0 0 0 0 0 0 0 0
3815 F 0 0 0 0 0 0 0 0
3816 F 0 0 0 0 0 0 0 0
3817 F 0 0 0 0 0 0 0 0
3818 F 0 0 0 0 0 0 0 0
3819 F 0 0 0 0 0 0 0 0
3820 F 0 0 0 0 0 0 0 0
                         

Positive control
(0.3% DNCB)

 3831 M 0 0 0 0 1 2 3 2
3832 M 0 0 + + 2 3 2 1
3833 M 1 1 + 0 1 2 3 2
3834 F 1 1 + + 2 1 2 2
3835 F 0 0 + + 3 3 3 3
                  L R L R
Negative control
(distilled water)		 3821 M 0 0 0 0 0 0 0 0 0 0
3822 M 0 0 0 0 0 0 0 0 0 0
3823 M 0 0 0 0 0 0 0 0 0 0
3824 M 0 0 0 0 0 0 0 0 0 0
3825 M 0 0 0 0 0 0 0 0 0 0
3826 F 0 0 0 0 0 0 0 0 0 0
3827 F 0 0 0 0 0 0 0 0 0 0
3828 F 0 0 0 0 0 0 0 0 0 0
3829 F 0 0 0 0 0 0 0 0 0 0
3830 F 0 0 0 0 0 0 0 0 0 0

L - Left flank (distilled water)

R == Right flank (MeNENA)

Table 3: Incidence and Severity of Responses at Challenge

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

Negative control-

Me-NENA

 0/10 0.0 0/10 0.0

Distilled water

 0/10 0.0 0/10 0.0

Positive control

 5/5 2.6 5/5 2.0

Table 4. Summary of Body Weights (g)

Test group
Animal Number Sex Initial Final
3801 M 357 583
3802 M 372 651
3803 M 393 670
3804 M 387 627
3805 M 373 619
3806 M 341 566
3807 M 353 560
3808 M 371 615
3809 M 361 628
3810 M 359 607
x   366.7 612.6
S.D.   15.72 35.13
N   10 10
3811 F 370 602
3812 F 350 551
3813 F 341 498
3814 F 336 465
3815 F 343 503
3816 F 359 523
3817 F 323 486
3818 F 334 476
3819 F 359 556
3820 F 349 498
x   346.4 515.8
S.D.   13.92 42.41
N   10 10

Negative control
Animal Number Sex Initial Final
3821 M 361 537
3822 M 348 567
3823 M 375 619
3824 M 364 600
3825 M 375 612
x   364.6 587.0
S.D.   11.24 34.34
N   5 5
3826 F 352 557
3827 F 356 551
3828 F 339 531
3829 F 327 434
3830 F 338 529
x   342.4 520.4
S.D.   11.68 49.82
N   5 5

Positive control
Animal Number Sex Initial Final
3831 M 364 530
3832 M 413 709
3833 M 348 525
x   375.0 588.0
S.D.   33.87 104.82
N   3 3
3834 F 351 553
3835 F 347 508
x   349.0 535.5
S.D.   2.83 31.82
N   2 2
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 (after previous dessication) at 300 mg/site moistened with 0.3 mL distilled water. 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 distilled water (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 distilled water 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.