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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
ethyl (2Z)-4,4,4-trifluoro-3-(methylamino)but-2-enoate
EC Number:
801-277-8
Cas Number:
507448-65-9
Molecular formula:
C7H10F3NO2
IUPAC Name:
ethyl (2Z)-4,4,4-trifluoro-3-(methylamino)but-2-enoate

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Biological Research Laboratories, Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: Young adult (approximately 1 - 3 months)
- Weight at study initiation: 336 - 433 g
- Housing: Individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): 13 - 14/hours
- Photoperiod (hrs dark / hrs light): 12/12 hours

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: refer to concentration section
Concentration / amount:

Intradermal Induction Pre-test: 0.5, 1.0, 3.0 and 5.0 % in peanut oil

Epidermal Induction Pre-test; 1, 5, 10, 20, 30, 50, 80 % in vaseline and 100 % (undiluted)

Day 0 – Intradermal Induction Injections: 5.0 % in peanut oil

Day 8 – Epidermal Application Induction: 80 % in Vaseline

Day 21 – Epidermal Challenge: 1 % in Vaseline
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: refer to concentration section
Concentration / amount:

Intradermal Induction Pre-test: 0.5, 1.0, 3.0 and 5.0 % in peanut oil

Epidermal Induction Pre-test; 1, 5, 10, 20, 30, 50, 80 % in vaseline and 100 % (undiluted)

Day 0 – Intradermal Induction Injections: 5.0 % in peanut oil

Day 8 – Epidermal Application Induction: 80 % in Vaseline

Day 21 – Epidermal Challenge: 1 % in Vaseline
No. of animals per dose:

Number of animals per group
Intradermal Induction Pre-test 1 male, 1 female
Epidermal Induction Pre-test 2 male, 2 female
Control Group 10
Test Group 20
Details on study design:

Pre-tests to Determine Concentrations

Intradermal Induction Pre-test
Pre-treatment: A 5 cm wide area in the neck-shoulder region of 1 male and 1 female animal was shaved approximately 1 hour before
treatment.
Treatment: Two pairs of intradermal injections (0.1 ml) of FCA and one pair of injections for each concentration were administered, one of each on each side of the spine.
Observations: The test sites were examined 24and 48 hours after administration to determine the highest concentration to produce
mild to moderate irritation without systemic toxicity.

Epidermal Induction Pre-test
Pre-treatment: Two pairs of intradermal injections (0.1 ml) of a 1:1 mixture of FCA/physiological saline were administered to
2 male and 2 female animals
Treatment: Seven days later, the seven test article/vehicle mixtures and the undiluted test article were applied with Hill Top Chambers on four animals. Two animals were applied 30, 50, 80 and 100 % in four chambers, two on each flank
Two animals were applied 1, 5, 10 and 20 % in four chambers, two on each flank.
Observations: The test sites were examined 24and 48 hours after administration to determine the highest concentration to
cause mild to moderate irritation for the induction application and no irritation for the challenge application
(highest non-irritant dose).

Maximisation Test Procedure:
The Maximisation test was conducted with 10 animals in the vehicle control group and 20 animals in the test article group.

A set of intradermal induction injections was made on Day 0. A epidermal induction application was made once on day 8. The challenge epidermal application was once on Day 21.

Day 0
Pre-treatment: An area 5cm x 5cm on the neck was shaved approximately 1 hour before treatment.
Treatment: Three pairs of injections 0.1ml in volume were given in the shaved area so that one of each pair was on each side of the midline.
Vehicle control group injections: (1) adjuvant/physiological saline mixture, 1:1 v/v
(2) peanut oil
(3) peanut oil, 50% v/v with 1:1 adjuvant/physiological saline mixture
Test article group injections: (1) adjuvant/physiological saline mixture, 1:1 v/v
(2) test article in peanut oil
(3) test article in1:1 adjuvant/physiological saline mixture

Day 8
Treatment: A filter paper patch was fully loaded approximately 0.4 g) with the test article/vehicle mixture
(test article group) or Vaseline vehicle alone (vehicle control group) and held in place with the occlusive
dressing for 48 hours.

Day 21
Pre-treatment: The flanks of the animals were shaved immediately prior to treatment.
Treatment: One chamber loaded with the test article/vehicle mixture (approximately 0.35ml) was placed on one flank
(test flank) and one chamber loaded with the vehicle alone was placed on the other flank (vehicle flank) of the
animals of both groups. The chambers were held in place with the occlusive dressing for 24 hours.

Observations and Records
Period of observation: Through 48 hours after completion of the challenge application.
Scoring Interval: 24 and 48 hours after removal of the dressing for the challenge application.
Grading of skin reactions: Dermal reactions graded according to the Draize Scale.
Clinical Observations: Checked daily.
Mortality: Checked daily.
Body weight: Immediately before treatment and at test termination.

Positive control substance(s):
yes
Remarks:
2-Mercaptobenzothiazole

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: Sensitization
Hours after challenge:
24
Group:
other: Control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: Sensitization. . Hours after challenge: 24.0. Group: other: Control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: Sensitization
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: Sensitization. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
other: Sensitization
Hours after challenge:
48
Group:
other: Control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: Sensitization. . Hours after challenge: 48.0. Group: other: Control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: Sensitiszation
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: Sensitiszation. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

 

Pre-tests, Intradermal Induction – The 5.0 % concentration was selected - For individual irritation scores refer to Table 1. 

Pre-tests, Epidermal Application – The 80 % concentration was selected for epidermal induction. The 1.0 % concentration was selected for the epidermal challenge - For individual irritation scores refer to Table 2. 

Skin Irritation Check – Positive skin irritation reactions were noted for all animals with the test article, there were no positive reactions among the vehicle control group.  For individual results refer to Table 3. 

Skin Reaction Following Challenge Application – There were no positive reactions at either the 24- or 48- hour readings for the test article or the vehicle control. Sensitization rate for the test article is therefore 0%. – Sensitization reactions are summarized in Table 4, for individual scores refer to Table 5 & 6.  

 

There was no mortality in the study. 

 

There were no remarkable clinical observations. 

 

Body weights were no affected. 

 

Applicant's summary and conclusion

Interpretation of results:
other: not required to be classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:

According to the test results, CA 2455 A (Intermediate of CGA 276854) is not required to be classified for skin sensitization according to Commission Directive 93/21/EEC, issued May 4, 1993.
Executive summary:

 

A dermal sensitization test was conducted with CA 2455 A (Intermediate of CGA 276854) (batch LOT 3) using the Maximization procedure. Two groups of guinea pigs (10 vehicle control, 20 test) were included. On day 0, the test group animals were given a set of intradermal injections (including 5.0% CA 2455 A (Intermediate of CGA 276854) in peanut oil for the test group). The epidermal induction application was made on day 8; the vehicle control animals were treated with the vehicle alone, and the test animals with 80% CA 2455 A (Intermediate of CGA 276854) in vaseline. The epidermal challenge application on day 21 consisted of a paired application of the vehicle alone and 1% CA 2455 A (Intermediate of CGA 276854) in vaseline in both groups. Skin reactions on both the vehicle and test flanks were scored 24 and 48 hours after completion of the challenge application, according to the Draize scale. 

 

There were no positive responses among either the vehicle control or test group animals on either the vehicle flank or the test flank; the sensitization rate for CA 2455 A (Intermediate of CGA 276854) was therefore 0 %. There was no mortality, and there were no remarkable clinical observations in any of the two groups. Body weights were not affected by treatment. 

 

According to the test results, CA 2455 A (Intermediate of CGA 276854) is not required to be classified for skin sensitization according to Commission Directive 93/21/EEC, issued May 4, 1993.