Registration Dossier

Administrative data

Description of key information

The test substance has no skin sensitising potential when tested in guinea pigs (OECD 406, GLP).

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:
13. September - 19. October 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
The modified Bühler test using 9 topical induction treatments was performed.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
at that time, 1988, the LLNA according to OECD guideline 429 was not yet developed and the guinea pig the preferred test animal
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, FRG
- Age at study initiation: 2 months
- Weight at study initiation: 314 - 460 g
- Housing: metal cages wit wire-mesh floors/ 2 animals per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: a combined acclimation period of 13 days was observed (7 days for the primary irritation animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 °C
- Humidity (%): 50-75

- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 13 September - 19 October 1988
Route:
epicutaneous, occlusive
Vehicle:
other: 1% methyl cellulose
Concentration / amount:
50% (w/w) in 1% methyl cellulose in milli-RO water
Route:
epicutaneous, occlusive
Vehicle:
other: 1% methyl cellulose
Concentration / amount:
50% (w/w) in 1% methyl cellulose in milli-RO water
No. of animals per dose:
A total of 35 female animals were allocated into different groups: one experimental group of 20 animals and one group of 10 animals representing the control. The remaining five animals were used for primary irritation experiments.
Details on study design:
RANGE FINDING TESTS:
The primary irritation experiments included an epicutaneous treatment of one animal with a single concentration (50 % w/w) of the test substance in aqueous methyl cellulose 1% (mainly to assess any toxic effects) and an application with four guinea pigs of several concentrations of the test substance: 50%, 25%, 10% and 5% (w/w) in aqueous methyl cellulose 1% (to assess primary irritancy). The first animal was exposed to 0.05 ml of each concentration using Square chambers, both applications for 24 hours. The treated skin of the first animal showed no irritation. No signs of systemic toxicity were observed in any of the five treated animals.


MAIN STUDY
A. INDUCTION EXPOSURE
Experimental animals were exposed to the test substance, suspended to a concentration of 50% (w/w) in 1% methyl cellulose in milli-RO water and control animals to the vehicle. The patch consisted of a piece of Metalline (approx. 2x3 cm), attached to aluminium foil by means of a bit of petrolatum, that was mounted on Sleek tape. On day 0, the experimental animals were clipped in an area of the skin on the back just behind the right shoulder girdle. Thereafter the animals were wrapped in a "window dressing" which consisted of Coban elastic bandage with an opening of approximately 2x3 cm above the clipped area. Immediately thereafter, the area was exposed to dry ice for 5 seconds and a patch with 0.2 ml test substance was applied for 48 hours. On day 2 the same application was repeated. On day 4, the dressing was removed and the exposed area was clipped again. A new patch with 0.2 ml test substance was applied for 6 hours. Further induction exposures were carried out on the same site with 0.5 ml of the test substance, with an exposure period of 6 hours on days 7, 9, 11, 14, 16 and 18. The patch was covered with Coban elastic bandage. After each application the remaining test substance was removed from the skin with a tissue moistened with tap-water and if necessary, the exposed skin was clipped.
The control animals were treated in a similar manner to the experimental animals, on the left flank from day 4 onwards, with the exception that only the vehicle was applied. The skin reactions were read at the end of the induction phase.


B. CHALLENGE EXPOSURE
Ten days after the last induction exposure (day 28), the experimental and control animals were challenged to 50% (w/w) of the test substance in 1% methyl cellulose in milli-RO water and to the vehicle alone. The application was made to the clipped and shaved left flank of the experimental animals and on the right flank of the control animals using the same volume and the same patch as in the induction phase, and held in place with an elastic
Positive control substance(s):
yes
Remarks:
37% formaldehyde solution
Positive control results:
A positive control experiment was carried out in May 1987. A sensitization rate of 50 per cent was obtained to the 1% formaldehyde
concentration
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 % test substance in vehicle for challenge
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 % test substance in vehicle for challenge. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% test substance in vehicle for challenge
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% test substance in vehicle for challenge. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% test substance in vehicle for challenge
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% test substance in vehicle for challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% test substance in vehicle for challenge
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% test substance in vehicle for challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitising potential of the test substance was investigated in the Buehler test with Dunkin-Hartley guinea pigs according to OECD TG 406 and GLP. The experimental group consisted of 20 animals and 10 animals were used as a control group. The animals were subjected to nine epicutaneous occlusive induction exposures with the test substance as a 50% (w/w) suspension in 1 % methyl cellulose and milli-RO water. The control animals were treated with the vehicle alone. Ten days after the last induction treatment, all animals were challenged with the test substance at a concentration of 50% (w/w) in the same vehicle. A positive control (formaldehyde solution) tested in a separate test showed significant positive results in the same test system. Following challenge application, no dermal reactions were seen in any of the test or control animals. No death occurred during the study, no systemic symptoms were observed and body weight gain of all animals was not affected by the treatment. All scores were 0 in the negative control group and in the test group 24 and 48 hours after patch application. Consequently the test substance was considered as non sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results of the skin sensitising study, the test substance is not subject to classification and labelling according to Directive 67/548/EEC and Regulation 1272/2008/EC.