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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation
Adequacy of study:
other information
Study period:
Start of the experimental phase: March 11, 2015; Termination of the in-life phase: September 26, 2015
Rationale for reliability incl. deficiencies:
other: Well documented GLP guideline study on a well characterized test material.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
- Name of test material (as cited in study report): Flocryl™ ADAM/BZCL 80%
- Substance type: Organic
- Physical state: Colorless liquid
- Analytical purity: Monomer concentration: 80.7%
- Impurities: Water (>19%)
- Composition of test material, percentage of components: 80.7
- Purity test date: 12/02/2015
- Lot/batch No.: ADBZ-5-05-15-08-E
- Expiration date of the lot/batch: not available
- Stability under test conditions: Stable
- Storage condition of test material: +10°C to +25°C

In vivo test system

Test animals

Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: 34 to 36 days
- Weight at study initiation: 295 g to 348 g (excluding positive control group); positive control group: 320 g to 374 g
- Housing: The animals were kept in groups of 5 in MAKROLON cages (MZK 80/25)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum (in drinking bottles)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22% ± 3%
- Humidity (%): 55% ± 15%
- Air changes (per hr): 15 to 20 times per hour
- Photoperiod (hrs dark / hrs light): 12-hour light / 12-hour dark cycle

IN-LIFE DATES: From: July 01, 2015 (main study) To: September 26, 2015

Study design: in vivo (non-LLNA)

Induction
Concentration / amount:
First run:
intradermal: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 25% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 50% in the supplied material in aqua ad iniectabilia

Second run:
intradermal: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 25% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
Challenge
Concentration / amount:
First run:
intradermal: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 25% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 50% in the supplied material in aqua ad iniectabilia

Second run:
intradermal: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 25% of the supplied material in aqua ad iniectabilia
epicutaneous: Flocryl™ ADAM/BZCL 80% at a concentration of 1% of the supplied material in aqua ad iniectabilia
No. of animals per dose:
First run:
Group 1 (vehicle control): 5 animals
Group 2 (Flocryl™ ADAM/BZCL 80%): 10 animals

Second run:
Group 3 (vehicle control): 5 animals
Group 4 (Flocryl™ ADAM/BZCL 80%): 10 animals

Group 5 (positive control): 20 animals
The positive control data are obtained from the historical backgroud of the laboratory. The positive control group was not tested concurrently with this study but is a historical background group from a study performed during May/June 2015.

Details on study design:
RANGE FINDING TESTS:
- No. of animals: 18 male animals (intradermal: 2 animals, epicutaneous: 16 animals)
- Exposure period: epicutaneous: 24 hours and 48 hours
- Test groups: intradermal: 1 group with 2 animals; epicutaneous: 2 groups with 4 animals each (24-hour and 48-hour exposure) and 1 group with 8 animals (pre-treatment with sodium laurylsulfat on the day before administration and 48-hour topical administration)
- Site: intradermal: shoulder region; epicutaneous: flanks
- Concentrations: intradermal: 0.01, 0.1, 0.5, 1, 5, and 10% Flocryl™ ADAM/BZCL 80%; epicutaneous (24-hour and 48-hour exposure, without sodium laurylsulfat): 1, 5, 10, 25, 50, 75, and 100 % Flocryl™ ADAM/BZCL 80%; epicutaneous (48-hour exposure, pre-treatment with sodium laurlysulfat) 10, 25, 50, and 75% Flocryl™ ADAM/BZCL 80%
- Evaluation (hr after challenge): intradermal: 24 hours, 48 hours, and 72 hours after start of treatment: epicutaneous (24-hour and 48 hour exposure, without laruyl sulfat): 24 hours, and/or 48 hours and 72 hours; epicutaneous (48-hour exposure; pre-treatment with sodium laurylsulfat)


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: day 0: 3 pairs of intradermal injection(Freund's complete adjuvant (FCA), Flocryl™ ADAM/BZCL 80% (1% in aqua ad iniectabilia), and Flocryl™ ADAM/BZCL 80% (in a 1 + 1 mixture (v/v) FCA/physiological saline);
day 7: epicutaneous: 48-hour exposure time
- Test groups: group 2 (first run) and group 4 (second run)
- Control group: group 1 (first run) and group 3 (second run)
The vehicle control animals were treated in the same way as the animals of the test group, but received aqua ad iniectabilia instead of the test item.
- Site: intradermal: shoulder region; epicutaneous: shoulder region
- Frequency of applications: day 0 (intradermal) and day 7 (epicutaneous)
- Duration: evaluation after 24 and 48 hours after start of exposure (day 0) and after 48 and 72 hours after start of exposure (day 7)
- Concentrations: First and second run: day 0: intradermal: 1% Flocryl™ ADAM/BZCL 80%; day 7: epicutaneous 25% Flocryl™ ADAM/BZCL 80%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 hours
- Test groups: group 2 (first run) and group 4 (second run)
- Control group: group 1 (first run) and group 3 (second run)
- Site: test item: left flank; vehicle: right flank
- Concentrations: First run: 50% Flocryl™ ADAM/BZCL 80%; second run: 1% Flocryl™ ADAM/BZCL 80%
- Evaluation (hr after challenge): first evaluation: 48 hours after the start of the challenge; second evaluation: 72 hours after the start of the challenge

OTHER: day 6: treatment with 0.5 mL sodium laurylsulfat 10% in vaseline

Results and discussion

Positive control results:
Animals treated with alpha-hexyl cinnamic aldehyde in sesame oil exhibited a sensitising reaction in all animals in form of a disrete or patchy erythema (grade 1) or a moderate and confluent erythema (grade 2) 48 hours after start of the challenge exposure.

In vivo (non-LLNA)

Resultsopen allclose all
Hours after challenge:
24
Dose level:
aqua ad iniectabilia
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 24.0. Dose level: aqua ad iniectabilia. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Hours after challenge:
48
Dose level:
aqua ad iniectabilia
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: aqua ad iniectabilia. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Hours after challenge:
48
Dose level:
aqua ad iniectabilia
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: aqua ad iniectabilia. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: discrete or patchy erythema.
Hours after challenge:
72
Dose level:
aqua ad iniectabilia
No. with + reactions:
5
Total no. in group:
5
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: aqua ad iniectabilia. No with. + reactions: 5.0. Total no. in groups: 5.0. Clinical observations: discrete or patchy erythema.
Hours after challenge:
72
Dose level:
aqua ad iniectabilia
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: aqua ad iniectabilia. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Hours after challenge:
24
Dose level:
1% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: . Hours after challenge: 24.0. Dose level: 1% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: moderate and confluent erythema.
Hours after challenge:
48
Dose level:
1% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: 1% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: moderate and confluent erythema.
Hours after challenge:
48
Dose level:
25% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: 25% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: moderate and confluent erythema.
Hours after challenge:
72
Dose level:
25% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: 25% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: moderate and confluent erythema.
Hours after challenge:
48
Dose level:
1% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: 1% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Hours after challenge:
72
Dose level:
1% Flocryl™ ADAM/BZCL 80%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: 1% Flocryl™ ADAM/BZCL 80%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Hours after challenge:
24
Dose level:
α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 24.0. Dose level: α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Hours after challenge:
48
Dose level:
α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Hours after challenge:
48
Dose level:
α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
moderate and confluent erythema
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: moderate and confluent erythema.
Hours after challenge:
72
Dose level:
α-hexyl cinnamic acid
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: α-hexyl cinnamic acid. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Hours after challenge:
48
Dose level:
α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema (10 animals) or moderate and confluent erythema (10 animals)
Remarks on result:
other: . Hours after challenge: 48.0. Dose level: α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema (10 animals) or moderate and confluent erythema (10 animals).
Hours after challenge:
72
Dose level:
α-hexyl cinnamic aldehyde
No. with + reactions:
13
Total no. in group:
20
Clinical observations:
discrete or patchy erythema
Remarks on result:
other: . Hours after challenge: 72.0. Dose level: α-hexyl cinnamic aldehyde. No with. + reactions: 13.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema.
Clinical observations:
Results of first run see below
Remarks on result:
other: Clinical observations: Results of first run see below.

Any other information on results incl. tables

First run:

A first attempt of the main study using a 1% concentration in aqua ad iniectabilia for the first (intradermal) stage, a 25% concentration in aqua ad iniectabilia for the second (epicutaneous) induction stage with sodium laurylsulfat pre-tretment and a 50% concentration in aqua ad iniectabilia for the challenge resulted in a moderate and confluent erythema in all 10 animals 48 and 72 hours after start of the challenge and a decrease of body weight gain in the test item-treated animals compared to the control. This response was similar to that in the induction phase of the study. After discussion with the Study Monitor the study was re-run with a 1% concentration in aqua ad iniectabilia for first (intradermal) stage, a 25% concentration in aqua ad iniectabilia for the second (epicutaneous) induction stage with sodium laurylsulfate pre-treatment and a 1% concentration in aqua ad iniectabilia for the challenge.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, the substance revealed no sensitising properties in guinea pigs in a test model according to MAGNUSSON and KLIGMAN.