Reaction product of Aminoguanidine bicarbonate and Tall Oil fatty acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-documented GLP study, performed in accordance with the OECD Guideline 406 (Skin Sensitisation).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Remarks:

Two deviations: purity & stability not determined; achieved concentration not determined by analysis

Type of study:

Buehler test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-600-9

EC Name:

-

Molecular formula:

The substance is a UVCB for which it is not possible to provide a molecular formula

IUPAC Name:

(9E)-N-[(N'-hexadecanoyloctadecanehydrazido)methanimidoyl]octadec-9-enamide

Details on test material:

Description: Complex reaction product of an aminate base-carbonate and fatty acids
Chemical name: HiTEC 7134 Performance additive
- Physical state: viscous liquid
- Storage condition of test material: ambient temperature in the dark

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall, Newchurch, Burton-on-Trent, Staffs, UK
- Age at study initiation: young adults
- Weight at study initiation: 342-445 g
- Housing: five animals/cage
- Diet: ad libitum, FD1, Special Diet Services, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Induction 2

Concentration / amount:

Induction phase: 0.4 ml of 15% w/v preparation in corn oil
Challenge phase: 0.1-0.2 ml of 5% w/v preparation in corn oil

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

Induction phase: 0.4 ml of 15% w/v preparation in corn oil
Challenge phase: 0.1-0.2 ml of 5% w/v preparation in corn oil

No. of animals per dose:

20

Details on study design:

RANGE FINDING TESTS
Undiluted test substance and 75%, 50% and 25% w/v preparations of the test substance in corn oil were applied to the skin of two female guinea pigs. Irritation was detected in all concentrations. Further dose levels (15%, 10%, 5% and 3%) were tested. Slight irritation signs were observed at 15% and 10%, while no signs of irritation were seen after application of the two lowest doses. The 15% dose was selected as appropriate for the induction phase and the 5% for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: an area on the scapular region was clipped free of hair and a substance was applied through a lint patch; the patch was covered with an occlusie dressing
- Control group: similar to the test groups the same patch was used but soaked only in corn oil
- Site: scapular region 5X5 cm
- Frequency of applications: every 7 days
- Concentrations: 0.4 ml of 15% w/v preparation in corn oil

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 6 h
- Test groups: an area on the left flank was clipped free of hair, and a lint patch with the test substance was applied. An occlusive dressing was used
- Control group: treated identically to the test groups
- Site: 5X15 cm
- Concentrations: 0.1-0.2 ml of 5% w/v preparation in corn oil
- Evaluation (hr after removal of the dressings): 1 to 2 days

Challenge controls:

NA

Positive control substance(s):

yes

Remarks:

hexylcinnamaldhyde

Study design: in vivo (LLNA)

Concentration:

NA

No. of animals per dose:

NA

Details on study design:

NA

Statistics:

NA

Results and discussion

Positive control results:

Scattered mild redness or moderate and diffuse redness was seen in 17/20 tested animals (net sensitising response of 65%).

In vivo (non-LLNA)

Results

Results 1

Hours after challenge:

24

Group:

test chemical

Dose level:

10% w/v

No. with + reactions:

20

Total no. in group:

20

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 10% w/v. No with. + reactions: 20.0. Total no. in groups: 20.0.

Results 2

Hours after challenge:

24

Dose level:

10% w/v

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

(control group)

Remarks on result:

other: . Hours after challenge: 24.0. Dose level: 10% w/v. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: (control group).

Results 3

Hours after challenge:

24

Group:

test chemical

Dose level:

3% w/v

No. with + reactions:

20

Total no. in group:

20

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 3% w/v. No with. + reactions: 20.0. Total no. in groups: 20.0.

Results 4

Hours after challenge:

24

Dose level:

3% w/v

No. with + reactions:

6

Total no. in group:

10

Clinical observations:

(control group)

Remarks on result:

other: . Hours after challenge: 24.0. Dose level: 3% w/v. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: (control group).

Results 5

Hours after challenge:

24

Group:

test chemical

Dose level:

0.3% w/v

No. with + reactions:

18

Total no. in group:

20

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 0.3% w/v. No with. + reactions: 18.0. Total no. in groups: 20.0.

Results 6

Hours after challenge:

24

Dose level:

0.3% w/v

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

(control group)

Remarks on result:

other: . Hours after challenge: 24.0. Dose level: 0.3% w/v. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: (control group).

Results 7

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1% w/v

No. with + reactions:

8

Total no. in group:

20

Remarks on result:

other: . Hours after challenge: 24.0. Group: test group. Dose level: 0.1% w/v. No with. + reactions: 8.0. Total no. in groups: 20.0.

Results 8

Hours after challenge:

24

Dose level:

0.1% w/v

No. with + reactions:

7

Total no. in group:

10

Clinical observations:

(control group)

Remarks on result:

other: . Hours after challenge: 24.0. Dose level: 0.1% w/v. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: (control group).

Any other information on results incl. tables

Table 1: Challenge responses

Animal No	Sex	24 h	48 h		Animal No	Sex	24 h	48 h
237	F	1	0		252	F	0	0
238	F	1	1		253	F	0	0
239	F	0	0		254	F	0	0
240	F	0	0		255	F	0	0
241	F	0	0		256	F	1	1
242	F	0	0		257	F	0	0
243	F	0	0		258	F	0	0
244	F	1	1		259	F	0	0
245	F	0	0		260	F	0	0
246	F	1	1		261	F	0	0
247	F	1	1		262	F	0	0
248	F	0	0		263	F	0	0
249	F	1	0		264	F	0	0
250	F	1	1		265	F	0	0
251	F	0	0		266	F	0	0

257 -266: control group

237 -256: test group

Scale

0- No reaction

1- Scattered mild redness

2- Moderate and diffuse redness

3- Intense redness and swelling

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

HiTEC 7134 was tested for its skin sensitisation potential on guine pigs in accordance with the Buehler test. The results revealed that the test material shall be considered as a skin sensitiser under the specific test conditions.

Executive summary:

The sensitisation potential of HiTEC 7134 was assessed using a method based on that described by Ritz and Buehler (1980). The test substance in corn oil was applied dermally to 20 female Dunkin-Hartley guinea pigs. Ten animals were used as controls. The study involved an initial induction phase and a sequential challenge phase. Concentrations applied topically during the two phases were as follows: 0.4 ml of 15% w/v preparation in corn oil during induction, and 0.1-0.2 ml of 5% w/v preparation in corn oil during the challenge phase. The sensitisation response of the animals was determined 1 and 2 days after challenge by assessing the degree of erythrema. The study was performed in accordance with the OECD Guideline 406 (Skin Sensitisation). The challenge of the previously-induced animals with H7134 exerted a moderate skin sensitisation response in eight out of the 20 animals, expressed as scattered mild redness. Such effects were not seen in any of the control animals. The net response was 40% and based on the classification criteria H7134 shall be classified as a skin sensitizer.