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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Test item: N-(2-HYDROXYETHYL) PHTHALIMIDE
CAS No.: 3891-07-4
Physical state: solid, powder
Colour and Odour: white, odourless
Active Ingredient Content (TLC): 98.95 %
Storage: on dry place, protected from light, 15-30 °C

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Species and strain: CBA/Ca mice
Source: TOXI-COOP ZRT.
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Number of animals: 28 animals/main test (4 animals/treatment group)
Sex: Female, nulliparous, non-pregnant
Age of animals: Young adult mice; 10-12 weeks old (at start of the main test)
Body weight range at starting: 18.7-23.8 g
Animal health: Only healthy animals were used
Acclimatization time: 14 days
Animal health: Only healthy animals were used

Housing during acclimatization period: Grouped caging in small groups
Housing during the test: Grouped caging (4 animals/cage)
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 – 70 %

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Remarks:
AOO (acetone:olive oil, 4:1) for positive control
Concentration:
The test item was administered at four different concentrations (25; 10; 5; 2,5 w/v%) according to the results of the dose range finding test.
No. of animals per dose:
4 animal/dose
Details on study design:
Selection of test item concentrations was based on the results of a formulation evaluation and also results of preliminary irritation/toxicity tests to find an appropriate solvent and the maximum applicable concentration according to the relevant guidelines. Based on the preliminary test results the test item was examined in the main test at 25 %, 10 %, 5 % and 2.5 % (w/v) concentrations as formulations in the selected vehicle of N,N-Dimethylformamide (DMF). Appropriate positive control (α-Hexylcinnamaldehyde [HCA] in 25 % (w/v) concentration), furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed.
The positive control item (25 % (w/v) HCA in Acetone: Olive oil 4:1 (v/v) mixture, AOO) induced the appropriate stimulation over the control, thus confirming the validity of the assay.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The positive control group animals were treated with 25 % (w/v) HCA solution (dissolved in AOO) concurrent to the test item groups. No mortality, cutaneous reactions or signs of toxicity were observed in the positive control group.
Significant lymphoproliferative response (SI ≥ 3) was noted for HCA (SI = 13.7). The results of the positive control item demonstrated appropriate performance of the test in accordance with the relevant guidelines and confirmed validity of the assay.

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Remarks:
25% in DMF
Value:
0.6
Key result
Parameter:
SI
Remarks:
10% in DMF
Value:
1
Key result
Parameter:
SI
Remarks:
5% in DMF
Value:
2.2
Key result
Parameter:
SI
Remarks:
2.5% in DMF
Value:
1.6

Any other information on results incl. tables

Test Group Name

Measured

DPM/group

Group*

DPM

DPN

(DPN/Node)

Stimulation

Index Values

Vehicle control for the positive control: AOO

4208

4117.0

514.6

1.0

Positive control:
25 % HCA
in AOO

56520

56429.0

7053.6

13.7

N-(2-HYDROXYETHYL) PHTHALIMIDE
25 %
in DMF

1763

1672.0

209.0

0.6

N-(2-HYDROXYETHYL) PHTHALIMIDE
10 %
in DMF

2785

2694.0

336.8

1.0

N-(2-HYDROXYETHYL) PHTHALIMIDE
 
5 % in DMF

5883

5792.0

724.0

2.2

N-(2-HYDROXYETHYL) PHTHALIMIDE
 
2,5 % in DMF

4130

4039.0

504.9

1.6

Vehicle control for the test item: DMF

2679

2588.0

323.5

1.0

 *Group DPM = measured DPM(group)- average DPM(background)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
In conclusion, under the conditions of the present Local Lymph Node Assay, N-(2-HYDROXYETHYL) PHTHALIMIDE (CAS No. 3891-07-4) tested at the maximum attainable concentration of 25 % and at concentrations of 10 %, 5 % and 2.5 % (w/v) as formulations in an appropriate vehicle (DMF) was shown to have no skin sensitization potential.