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Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
animals housed in groups of 5 instead alone
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1981
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was initiated prior to the implementation of the LLNA method.

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
428-040-8
EC Name:
-
Cas Number:
138261-41-3
Molecular formula:
C9H10ClN5O2
IUPAC Name:
2-chloro-5-{[2-(nitroimino)imidazolidin-1-yl]methyl}pyridine
Test material form:
solid: crystalline

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Laboratory animal breeder Winkelmann, Borchen, Germany
- Age at study initiation: 5 - 8 weeks
- Weight at study initiation: 309 - 403 g
- Housing: in groups of 5 in Makrolon type IV cages, equipped with low-dust wood granules as bedding material (Bogner GmbH, Solingen, Germany)
- Diet: Altromin 3022 Diet for Guinea Pigs (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): approx. 50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12
- IN-LIFE DATES: the study was carried out in June 1987

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Cremophor EL (2% v/v) in sterile physiological saline solution
Concentration / amount:
1%
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: Cremophor EL (2% v/v) in sterile physiological saline solution
Concentration / amount:
25%
Day(s)/duration:
2 x 24h
Adequacy of induction:
highest technically applicable concentration used
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Cremophor EL (2% v/v) in sterile physiological saline solution
Concentration / amount:
3% / 25%
Day(s)/duration:
3 weeks after induction for 24h
Adequacy of challenge:
other: highest concentration that could be suspended (25%) and a concentration of a factor of 10 lower (3%)
No. of animals per dose:
10 (control), 20 (test substance)
Details on study design:
RANGE FINDING TESTS:
The choice of dose used in the treatment for induction and challenge was based on results obtained in preliminary studies, as reported in the annex. In these studies local and systemic tolerance following intradermal and epicutaneous treatment was tested, and the threshold concentration for the primary irritant effect of the test article determined.
The following concentrations were determined:
Intradermal induction: 1%
Topical induction: 25%
Challenge: 3% / 25%
The highest concentration that could be suspended (25%), as well as a concentration a factor of 10 lower (3%) was used. As the challenge was performed using two concentrations simultaneously, the second challenge was not necessary and the second control group was not used.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: single injection (intradermal), 2 x 24h (epicutaneous)
- Test groups:
Intradermal (3 injection sites)
1) Freund's complete adjuvant 1:1 diluted with sterile physiological saline
2) 1% test substance formulated with Cremophor EL (2% v/v) in sterile physiological saline
3) 1% test substance formulated as above and Freund's complete adjuvant in equal parts
Epicutaneous: 25% test substance

- Control group:
1) Freund's complete adjuvant 1:1 diluted with sterile physiological saline
2) Cremophor EL (2% v/v) in sterile physiological saline
3) Cremophor EL (2% v/v) in sterile physiological saline and Freund's complete adjuvant in equal parts
Epicutaneous: sterile physiological saline

- Site: backs and flanks
- Frequency of applications: once each
- Duration: 2 x 24h (epicutaneous)


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: 24h
- Test groups: 3 and 25 % test item on the left flank, vehicle only on the right flank
- Control group: 3 and 25 % test item on the left flank, vehicle only on the right flank
- Concentrations: 3 and 25%
- Evaluation (hr after challenge): 24 and 48 h

Additional information on cutaneous exposure
The animals were teated with 0.5 mL sodium lauryl sulfonate (10%, in vaseline) one day prior to epicutaneous induction, in order to induce local skin irritation.
Positive control substance(s):
yes
Remarks:
laboratory control data for formaldehyde are provided in the study report

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 5% challenge: 2%
No. with + reactions:
9
Total no. in group:
18
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
induction: 5% challenge: 0.2%
No. with + reactions:
3
Total no. in group:
18
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0% challenge: 25%
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:
test chemical
Dose level:
induction: 25% challenge: 3%
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:
negative control
Dose level:
induction: 0% challenge: 3%
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:
test chemical
Dose level:
induction: 25% challenge: 3%
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:
test chemical
Dose level:
induction: 25% challenge: 25%
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:
negative control
Dose level:
induction: 0% challenge: 25%
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:
test chemical
Dose level:
induction: 25% challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Body weight

The body weights of the treatment group animals corresponded to those of the control animals. A slight reduction in body weight of the animals was found in both groups at the end of the study, this is considered due to the treatment technique used (occlusive dressing).

 

General examination/clinical signs

The treatment was tolerated by all animals without any signs occurring.

 

Mortality

There were no mortalities.

 

Positive control data (M-027579-01-1)

Formaldehyde (reported on 01 Feb 1985)

1st challenge: 2%
Number of animals with skin reactions (corrected values): 7/20 (test article group); 0/10 (control group)

2nd challenge: 0.5%
Number of animals with skin reactions (corrected values): 7/20 (test article group); 0/10 (control group)

The results were evaluated by subtracting the number of reacting animals on the control side from the number of reacting animals on the test article side. This was performed for the animals in the test article group, as well as for those in the control group. The resulting values represent the corrected values as given above.

 

Positive control data (M-121846-01-1)

Formaldehyde (reported on 20 Jul 1987 )

1st challenge: 2%
Number of animals with skin reactions (corrected values): 8/18 (test article group); 0/10 (control group)

2nd challenge: 0.2%
Number of animals with skin reactions (corrected values): 3/18 (test article group); 0/10 (control group)

The results were evaluated by subtracting the number of reacting animals on the control side from the number of reacting animals on the test article side. This was performed for the animals in the test article group, as well as for those in the control group. The resulting values represent the corrected values as given above.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The study is in accordance to OECD TG 406, was performed under GLP conditions and is considered valid and reliable. Under the conditions tested, the test item did not induce skin sensitization in guinea pigs. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item for skin sensitisation is required.