Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
17 March - 21 April 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study with acceptable restrictions. No data on reliability check included.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no positive control data is included
GLP compliance:
yes
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Propylene Glycol Diacetate
- Analytical purity: > 99.5%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Thirty-five adult female guinea pigs of the Dunkin-Hartley strain, SPF quality, were obtained from Olac, Bicester, England. Date of arrival at the animal house: 05-03-'86. Four days before the start of the experiment, the body weights ranged from 278 to 369 g and the age was 1-2 months. The animals were housed in metal cages with wire-mesh floors (RUCO, Valkenswaard; 4 animals per cage). They were fed standard guinea pig diet, including ascorbic acid (1600 mg/kg), obtained from Hope Farms, Woerden (LC 23-B, pellet diameter 4 mm) and had free access to tap-water. In addition, once a week hay was provided. The animal room temperature was between 19.5 and 21.5C and the relative humidity between 30 and 70 per cent. The artificial light sequence was 12 hours light, 12 hours dark. A quarantine/acclimation period of 12 days was observed.

Thirty animals were allocated at random to two groups: one experimental group of 20 animals (group A) and one group of 10 animals representing the control group (B). The remaining 5 animals represented the primary irritation group.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Induction: 25%
Challenge: 0, 1, 5 and 25%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
Induction: 25%
Challenge: 0, 1, 5 and 25%
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
Suitable concentrations of the test substance for the induction and the challenge phases were determined in the primary irritation study. Four animals were exposed at one flank to the test substance, diluted in propylene glycol (Pro Analysis, blerck-Schuchardt FRG) to 25%, 10%, 2.5% and 1% (V/V), using Square chambers (v.d. Bent, Brielle, The Netherlands). The period of exposure under this occlusive dressing was 6 hours. The patches were kept in place with elastic bandage. After removal of the bandage, the exposed skin area was scored for the occurrence of erythema. Since no skin reactions were observed the experimental animals were exposed to 25% (V/V) PGDA in propylene glycol during the induction phase, which is usual ly the highest concentration used.

Induction phase
Experimental animals were exposed to 0.5 ml of the test substance, 25% (V/V) in propylene glycol, by repeated occluded application to the same site of the scapula region (left side). The closed patch (as described above), with test material applied only for the experimental group, remained in place for 6 hours. These applications were made 9 times during a period of 3 weeks (days 0, 2, 4, 7, 9, 11, 14, 16 and 18). After each application the remaining test substance was removed from the skin with a tissue. The control animals were treated with the vehicle, propyl ene glycol, according to the same procedure.

Challenge phase
Ten days after the last induction exposure (day 28), the experimental and control animals were challenged by application of 0.05 ml of a series of test substance concentrations in propylene glycol (25, 5, 1 and 0% V/V) to the clipped skin of the right flank by means of Square chambers. The challenge sites of experimental and control animal s were examined for sensitization 24 and 48 hours after removal of the dressings. The skin reactions in the experimental groups were assessed in relation to the findings in control animals and were scored according to the following numerical scoring system:
no skin reaction........................................................0
red spots (scattered reactions) ............................ 1
moderate and diffuse reaction. ........................2
redness and swelling ................. ................. 3
intensive reddening and swelling ...... ................ 4
Scores of 2 and more were considered positive. Any signs of general toxicity and local effects other than those indicated above were recorded.
Challenge controls:
One group of 10 animals representing the control group (B).
Positive control substance(s):
no

Results and discussion

Positive control results:
No data

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0% Challenge: 0, 1, 5 and 25%
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: Induction: 0% Challenge: 0, 1, 5 and 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Induction: 25% Challenge: 0, 1, 5 and 25%
No. with + reactions:
2
Total no. in group:
19
Clinical observations:
Diffuse skin reddening at the skin site exposed to 25% (v/v)
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 25% Challenge: 0, 1, 5 and 25%. No with. + reactions: 2.0. Total no. in groups: 19.0. Clinical observations: Diffuse skin reddening at the skin site exposed to 25% (v/v).
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0% Challenge: 0, 1, 5 and 25%
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: Induction: 0% Challenge: 0, 1, 5 and 25%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Induction: 25% Challenge: 0, 1, 5 and 25%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Induction: 25% Challenge: 0, 1, 5 and 25%. No with. + reactions: 0.0. Total no. in groups: 19.0.

Any other information on results incl. tables

One animal died from bandage-induced stress during the induction phase. Apart from the diffuse skin reddening at the skin site exposed to 25% (V/V) PGDA in propylene glycol observed in animal 2465 and 2478 on day 29, no positive reactions were observed. Moreover, the complete disappearance of skin reddening 24 hours later might indicate that the effects were not due to sensitization. The control sites and the skin of control animals revealed no reactions. Therefore, a sensitization rate of 2/19 x 100% = 10.5% is obtained. Concluding from these results and applying the general classification and 1abeling requirements for dangerous substances (Annex VI of the EEC Council Directive 67/548/EEC) the test substance need not be labelled as a skin sensitizer.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified