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Toxicological information

Skin sensitisation

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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:
19-Jun-1997 to 04-Sep-1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study. The study is a read across from tetradecanol (CAS 112-72-1).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Kalcol 4098
- Substance type: no data
- Physical state: no data
- Analytical purity: =98%
- Impurities (identity and concentrations): no data
- Purity test date: no data
- Lot/batch No.: 2036
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature in the dark
- Other: test substance was supplied by the Biological Science Laboratories of Kao Corporation

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Shizuoka
- Age at study initiation: 5 weeks
- Weight at study initiation: 313-337 g
- Housing: animals were housed in aluminium cages with stainless steel wire mesh floors (350 mm x 400 mm x 200 mm, Natsume Seisakusyo Co., Tokyo); 5 animals/cage.
- Diet (e.g. ad libitum): standard pelleted diet for guinea-pigs (RC-4; Oriental Yeast Co.) ad libitum
- Water (e.g. ad libitum): filtered tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):23±2
- Humidity (%): 50±10
- Air changes (per hr): 17
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12hrs light

IN-LIFE DATES: 19-Jun-1997 to 04-Sep-1997

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: liquid paraffin
Concentration / amount:
Induction: 5% (w/w) intracutaneous, 50% (w/w) epicutaneous occlusive
Challenge: 3% (w/w) and 10% (w/w)
No. of animals per dose:
10 test animals, 5 control animals
Details on study design:
RANGE FINDING STUDY: A preliminary test was performed to assess primary skin irritation using 8 female guinea-pigs. Test substance was administered to four animals by intradermal injection (10%, 5%, 3%, 1%, 0.3% and 0.1% w/w) and to four animals by 24-hr occluded patch. The number of animals showing skin irritation was recorded at 24, 48 and 72 hrs after intradermal treatment and at 3, 24 and 48 hrs after occluded patch testing. The results of this test were used to determine the doses for intradermal injection, topical induction and topical challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 - intracutaneous, followed by epicutaneous 7 days later
- Exposure period: 21 days between initial induction and challenge
- Test groups: 10 females
- Control group: 5 females
- Site: intracutaneous - intradermal injections were performed in the shaved skin area on both sides of the midline in the scapular region; epicutaneous - occlusive patches were applied to the previously treated areas
- Frequency of applications: intracutaneous induction followed by epicutaneous induction 1 week later
- Duration: epicutaneous induction - 48 hrs
- Concentrations: 5% intracutaneous, 50% epicutaneous

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2
- Exposure period: 24 hrs
- Test groups: 10 females
- Control group: 5 females
- Site: flank
- Concentrations: 3%, 10 % (w/w)
- Evaluation (hr after challenge): 24, 48 hrs

OTHER:
Grading system used for evaluation of patch test results (Magnusson and Kligman) : 0 = no visible change, 1 = discrete or patch erythema; 2 = moderate and confluent erythema; 3 = intense erythema and swelling.

MAIN STUDY
Induction:
(Day 0) Intradermal injections of 0.1ml of each of following: (a) 1:1 (v/v) emulsion of Freund’s complete adjuvant (FCA) and physiological saline, (b) 5% (w/w) of the test substance in liquid paraffin, and 1:1 (v/v) emulsion of 10% (w/w) test substance in FCA and physiological saline.
(Day 7) Occluded patches of 0.2 ml 50% (w/w) of the test substance in liquid paraffin were applied for 48 hrs.
Challenge:
(Day 21) Occluded patches of 0.1 ml of each of the 10%, 3% (w/w) of the test substance in liquid paraffin and liquid paraffin alone were applied for 24 hrs.
Challenge controls:
Five female animals were administered intradermally: 0.1 ml of liquid paraffin and 0.1 ml of an emulsion of Freund’s complete adjuvant (FCA) and physiological saline. Seven days later an occluded patch of liquid paraffin was applied for 48 hrs. At the challenge exposure, occluded patches of paraffin were applied to the animals flanks for 24 hrs.
Positive control substance(s):
yes
Remarks:
DNCB and formalin, not concurrent

Results and discussion

Positive control results:
Evidence presented over a relevant time period that the strain of guinea pig did respond to known sensitisers.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
3% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 3% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test. .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: There were reportedly no significant differences in general condition and body weight gain between test and control groups over the course of the test .

Any other information on results incl. tables

RESULTS OF RANGE FINDING STUDY:

Following intradermal injection, skin irritation was seen at concentrations of 10% and 5% persisting for 72 hours

but less marked at the lower concentration. The 3% concentration showed evidence of irritation at 24 hours in oneanimal only. Lower concentrations from 0.1 -1% showed no irritation. Following topical application slight irritation was seen in 2/4 animals at 50% only.

TEST: There was no evidence of sensitisation in any of the test or control animals at either challenge concentration

 

Table 1. Summary of the delayed contact hypersensitivity study of KALCOL 4098 in female guinea-pigs

 

Group

Number of animals showing positive reaction/Total number of animals

24 hrs after challenge

48 hrs after challenge

10%

3%

vehicle

10%

3%

vehicle

Test

0/10

0/10

0/10

0/10

0/10

0/10

Control

0/5

0/5

0/5

0/5

0/5

0/5

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Kalcol 4098 showed no evidence of being a skin sensitizer when tested using the Guinea pig maximization test in a reliable study conducted in accordance with OECD Guidelines 406. The study was GLP compliant. The study is a read across from tetradecanol (CAS 112-72-1).