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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:
key study
Study period:
2012-06-19 to 2012-07-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Well documented GLP study performed according to OECD Guideline 406 with some minor deviations (temperature and relative humidity levels) that no impact the outcome of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Temperature and relative humidity ranges were broader than indicated by the OECD Guideline, however there was no impact on study outcome; timing of scoring, however no impact on the study
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The Buehler test method is the non-adjuvant test given preference over other non-adjuvant methods in the OECD 406 guideline.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- State of aggregation : liquid
- Appearance : colourless to yellow brown
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 1J513
- Composition of test material, percentage of components: 0.08 wt % water

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature: 15-30°C

OTHER SPECIFICS:
- Name of test material (as cited in study report): JEFFCAT DMDEE
- Substance type: Colorless to yellow liquid
- Physical state: Liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elm Hill Breeding Laboratories
- Age at study initiation: 6 weeks (dose range); 7 weeks at start of dosing (day 1) of the main study
- Weight at study initiation: 343-373 grams (dose range); 336-458 grams at the outset (day 1) of the main study
- Housing: Animals were individually housed upon receipt. No other species were kept in the same room.
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Study animals were acclimated to their housing for a minimum of 5 and 7 days respectively for the dose range and main assay prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 26°C
- Humidity (%): 25 to 97%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: induction: ethanol; challenge: acetone
Concentration / amount:
Dose-range-finding study (primary irritation screen): four concentrations were dosed on four separate sites: 10%, 25%, 50% or 100%
Main assay: Based on the results of the dose-range-finding study, an induction dose and challenge dose of 100% (test item as received) was chosen for this study.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: induction: ethanol; challenge: acetone
Concentration / amount:
Dose-range-finding study (primary irritation screen): four concentrations were dosed on four separate sites: 10%, 25%, 50% or 100%
Main assay: Based on the results of the dose-range-finding study, an induction dose and challenge dose of 100% (test item as received) was chosen for this study.
No. of animals per dose:
Total number:
Dose range primary irritation: 4 (2 male/2 female)
Test article group: 20 (10 male/10 female)
Vehicle control group: 10 (5 male/5 female)
Positive control group: 6 (3 male/3 female)
Details on study design:
RANGE FINDING TESTS: Initially, a dose range was performed in four naive animals with the test article JEFFCAT DMDEE at 10%, 25%, 50% and 100% (as received). Based on these results, an induction dose and challenge dose of 100% (as received) was chosen for this study.

MAIN STUDY
A. INDUCTION EXPOSURE
For the induction phase of this study, twenty guinea pigs (10/sex) in the test article group were induced with three six-hour occluded dermal applications of JEFFCAT DMDEE (as received). A vehicle group of ten animals (5/sex) was induced in the same manner with 0.9% sodium chloride (saline). A positive control group of six animals (3/sex) was induced in the same manner as above with a known dermal sensitizer: 0.3 % 1-chloro-2,4-dinitrobenzene (DNCB) in 80% ethanol.

B. CHALLENGE EXPOSURE
Fourteen days after the last induction, all animals were dermally challenged with occluded applications at naive test sites. Animals in the test article and vehicle control group were challenged with JEFFCAT DMDEE (as received) and 0.9% sodium chloride (saline), respectively. One the day following the challenge, animals were depilated and approximately three hours later were scored for dermal irritation (24 hour). Scoring was repeated approximately 24 hours later for the 48 hour score.
Challenge controls:
Animals in the positive control group were challenged with 1-chloro-2,4-dinitrobenzene (DNCB) at 0.2% in acetone.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene

Results and discussion

Positive control results:
The positive control group, induced and challenged with DNCB, exhibited the anticipated positive responses at challenge, indicating that the methods employed in this study were valid.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Jeffcat DMDEE at 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Jeffcat DMDEE at 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No signs of systemic toxicity and all animals gained weight during the main study.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Saline
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Saline. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No signs of systemic toxicity and all animals gained weight during the main study.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
Jeffcat DMDEE at 100%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Jeffcat DMDEE at 100%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: No signs of systemic toxicity and all animals gained weight during the main study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
Saline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Saline. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No signs of systemic toxicity and all animals gained weight during the main study.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.2% DNCB in Acetone
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
1/6 with score 1, 5/6 with score 2; No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.2% DNCB in Acetone. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: 1/6 with score 1, 5/6 with score 2; No signs of systemic toxicity and all animals gained weight during the main study.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.2% DNCB in acetone
No. with + reactions:
6
Total no. in group:
6
Clinical observations:
1/6 with score 1, 5/6 with score 2; No signs of systemic toxicity and all animals gained weight during the main study
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.2% DNCB in acetone. No with. + reactions: 6.0. Total no. in groups: 6.0. Clinical observations: 1/6 with score 1, 5/6 with score 2; No signs of systemic toxicity and all animals gained weight during the main study.

Any other information on results incl. tables

Clinical observations:

There were no signs of systemic toxicity and all animals gained weight during the main study.

Challenge phase:

The positive control group, induced and challenged with DNCB, exhibited the anticipated positive responses at challenge, indicating that the methods employed in this study were valid.

All dermal irritation scores at the 24- and 48 -hour observations were zero for the vehicle control animals challenged with the test article and the vehicle (saline).

A single score of ± was recorded in the test article group at the test article site at 24 hours. All dermal irritation scores at the 48 -hour observations were zero for the test article group challenged with the test article and the vehicle (saline).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, induction with the test substance as received did not elicit a delayed contact hypersensitivity response in guinea pigs when challenged as received.