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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1992-06-18 to 1992-07-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
May 12, 1981
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A valid GPMT conducted according to guideline is available, which is reliable without restrictions and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: paste

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white Bor:DHPW (SPF)
Sex:
male/female

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
intradermal injection: 5 % in aqua ad inject
topical application: 25 % in aqua ad inject
Day(s)/duration:
intradermal: day 0 / epicutaneous: 7 days after intradermal for 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
10% in aqua ad inject.
Day(s)/duration:
day 21 / 24 h exposure
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (10 male, 10 female)
Details on study design:
RANGE FINDING TESTS:
- Intradermal injection:
The test article was diluted with aqua ad inject. and Freund's complete adjuvant (FCA; Sigma, 8024 Deisenhofen) to give a final concentration of 5 %.
Two animals were employed for the concentration tested, skin reactions were recorded 48 h after treatment.

- Dermal Application:
The test article was used undiluted. A closed patch exposure was effected by means of an occlusive bandage. Since this maximum concentration proved irritating, lower concentrations (75, 50, 25, 10 %) were tested. Ten animals were employed and skin reactions were recorded 48 h post applicationem.

MAIN STUDY
A. INDUCTION EXPOSURE (day 0)
- First stage -an area of 4 x 6 cm over the shoulders was clipped short with electric clippers and cleaned with 70 % (v/v) ethanol. Three pairs of intradermal injections were then made symmetrically in two rows on either side of the spine:
-- Test group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad inject.
2. 0.1 ml test article diluted in aqua ad inject (final concentration: 5 %)
3. 0.1 ml test article diluted in FCA /aqua ad inject (final concentration: 5 %)
-- Control group:
1. 0.1 ml FCA 50 % (w/w) diluted in aqua ad inject
2. 0.1 ml aqua ad inject. (undiluted)
3. 0.1 ml aqua ad inject 50 % (w/w) diluted in FCA

-- Second stage (day 7)
- 7 days after the intradermal injections the dermal application was initiated subsequent to reclipping of the area 24 hours before application of the test article at the highest concentration producing mild to moderate irritation, i.e. (25 % in aqua ad. inject). The test article was spread in a thick layer [to saturation] over a 4 x 5 cm patch (filter paper). The latter was firmly secured over the previous injection sites by an occlusive dressing for 48 h.
Control animals received a patch loaded with the vehicle alone.

B. CHALLENGE EXPOSURE (day 21)
Both control and test animals were subjected to a challenge exposure 14 days after the second stage of induction. The challenge test was performed on a 5 x 5 cm clipped and shaved area on each flank. The maximal non-irritating concentration of the test article (10 % in aqua ad iniect.) was applied to the left flank and the vehicle to the right using the patch technique described. In each case the duration of exposure was 24 h under an occlusive dressing. 24 and 48 h after patch removal, allergic responses were evaluated on a numerical scale according to Draize.

GRADING SYSTEM
Dermal reactions graded for erythema and edema according to grading scale:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges well defined by raising): 2
Moderate edema (raised approx 1 mm): 3
Severe edema (raised > 1 mm; beyond area of exposure): 4
Positive control substance(s):
yes
Remarks:
2,4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) are tested periodically. The last test with an acceptable level of response to each of these substances was performed in April 1992.

Results and discussion

Positive control results:
2,4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) are tested periodically. The last test with an acceptable level of response to each of these substances was performed in April 1992.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
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 group
Dose level:
10 %
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:
10 %
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
20
Reading:
other: periodically tested
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

RESULTS

Pilot study (range finding):

- Intradermal: No specific findings were observed.

- Dermal:

-- 100, 75 and 50 %: Partly well-defined erythema and slight oedema with induration of the treated areas were observed.

-- 25 %: Slight to well-defined erythema were observed.

-- 10 %: No skin reactions were observed, highest non-irritant concentration.

Main study:

Signs of irritation during induction:

At a concentration of 25 % slight to well-defined erythema and oedema were observed.

Challenge (conc. of test substance: 10 %, left flank) : The sensitization rate at 24 h and at 48 h was 0 %.

No reactions observed in control and test animals at 24 or 48h.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test article "partially unsaturated TEA-Esterquat" is considered to be a non-sensitizer in this study.
Executive summary:

In a dermal sensitization study according to OECD Guideline 406, May, 12 1981 with partially unsaturated TEA-Esterquat (a.i. 90 %, in isopropanol 10 %) diluted in water young adult Pirbright white guinea pigs (10 male, 10 female) were tested using the MAXIMIZATION TEST method.

Intradermal induction was performed with a 5 % test substance concentration. After dermal induction with 25 % solution of test substance, slight to well defined erythema and oedema was observed. None of the animals of the test group or control group showed any positive skin reactions after challenge treatment with a non-irritating test article concentration of 10 % in water. The sensitization rate at 24 h and at 48 h was 0 %.

The test article is considered to be a non-sensitizer in this study.