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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Aug 2006 to 30 Aug 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 404) performed in compliance with OECD GLP (1997)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD Guidelines 404 "Acute Dermal Irritation/Corrosion," adopted April 24, 2002 and Commission Directive 2004/73/EC, B.4 "Acute Toxicity: Dermal Irritation/Corrosion" April 29, 2004
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Name of test material (as cited in study report: MTDID 8191
- Structural formula attached as image file (if other than submission substance): see Fig.:
- Physical state: Yellowish liquid
- Analytical purity: > 98%:
- Lot/batch no.: FC 03/167
- Expiration date of the lot/batch: 31 Jan 2007:
- Storage condition of test material: Room Temperature and protected from light
- Other: Stable under storage conditions



Test animals

Species:
rabbit
Strain:
other: Young Adult New Zealand White Rabbit, SPF : male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV
- Age at study initiation: 10 - 11 weeks (2 females), 12 weeks (1 male)
- Weight at study initiation: 2.142 - 2.579 kg
- Fasting period before study: None
- Housing: Stainless steel cages with wood blocks (RCC Ltd.) and haysticks 4642 (Provimi Kliba AG) for gnawing
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water; ad libitum
- Acclimation period: 6 days (one female) or 7 days (one male and one female); under laboratory conditions after health examination
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: 16 Aug 2006 To: 30 Aug 2006

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: Hair clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 100% (undiluted)
VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
4-hour exposure
Observation period:
Observations were recorded at 24, 48, and 72 hours and at 7 days after exposure. Observations at 7 days were recorded in error and were not necessary for evaluation of irritation potential.
Number of animals:
3 total (1 male, 2 females)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage: 100%
- Type of wrap if used: Surgical gauze patch covered by semi-occlusive dressing
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, tap water
- Time after start of exposure: 4 hours
SCORING SYSTEM: Numerical scoring system listed in Commission Directive 2004/73/EC, April 29, 2004

Results and discussion

In vivo

Results
Irritation parameter:
other: Individual mean score
Basis:
mean
Time point:
other: 24, 48, and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
All scores were 0 at 24, 48, and 72 hours after patch removal as shown in Table 1.

Any other information on results incl. tables

Table 1. Primary Skin Irritation Results for MTDID 8191 Following a 4-hour Exposure in New Zealand White Rabbits

Animal Number

Sex

Evaluation Time

Erythema

Oedema

43

M

1 hour

1

0

44

F

2

0

45

F

1

0

43

M

24 hours

0

0

44

F

0

0

45

F

0

0

43

M

48 hours

0

0

44

F

0

0

45

F

0

0

43

M

72 hours

0

0

44

F

0

0

45

F

0

0

43

M

7 days*

0

0

44

F

0

0

45

F

0

0

* The 7-day observation was performed, but was not considered necessary for the evaluation of the results because all scores were 0 at 72 hours after dosing.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, MTDID 8191 is considered not irritating to rabbit skin.
Executive summary:

OBJECTIVE: MTDID 8191 (Batch No. FC 03/167) was tested in a primary skin irritation study to evaluate its irritation potential following a single dose to the skin of rabbits. METHODS: This study was conducted according to OECD GLP (1997) and Swiss GLP (2005). The study designed was in accordance with OECD 404 (2002) and Commission Directive 2004/73/EC, B.4. MTDID 8191, yellowish gel-like viscous substance, was applied at 0.5 grams to the intact left flank of young adult New Zealand white rabbits (n=3; 1 male, 2 females) and covered with semi-occlusive dressing. After 4 hours of treatment, the dressing was removed and the application sites were cleaned with lukewarm tap water. Scoring of skin reaction was performed 1, 24, 48, 72 hours, and 7 days after removal of the dressing. The individual mean score was calculated as the mean of the 24, 48, and 72 hour erythema/eschar or oedema observations for each animal. RESULTS: Erythema was observed at 1 hour after exposure (scores: 1, 2, and 1). No erythema was observed at 24 hours after exposure or through the remainder of the study. No oedema was observed at any time during the study. Individual mean scores (24 to 72 hours after exposure) were 0.0 for all three animals for both erythema/eschar and oedema. The 7-day observations were inadvertently performed and were considered unnecessary for evaluation, because all scores were 0 at 72 hours and 7 days after exposure. CONCLUSION: Based on the results of this study and EC Directive 2001/59/EC of August 2001, MTDID 8191 is considered not irritating to rabbit skin.