Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
20 April 2012 to 30 April 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
944127-07-1
IUPAC Name:
944127-07-1
Test material form:
other: solid (unspecified)
Details on test material:
- Appearance: White Solid
- Storage conditions of the test material: Ambient (18 to 36 °C)
- pH of test material: 4.60

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 to 9 months
- Weight at study initiation: 2.59 to 2.82 kg
- Fasting period before study: No
- Housing: The rabbits were housed individually in rabbit cages (size: approximately 65 cm long x 65 cm deep x 45 cm high) with a noryl shallow cage body and facilities for pelleted feed and drinking water. The litter collection trays (noryl waste tray) were changed daily (except on Sundays). A noryl perforated raised shelf was provided to the animals for enrichment.
- Diet (e.g. ad libitum): Rabbit feed was provided ad libitum in a stainless steel feed hopper.
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in a water filter-cum-purifier was provided to animals ad libitum in 750 mL bottles with sipper tubes. The water in the bottles was replenished once daily and the water bottles were changed once a week.
- Acclimation period: Five or six days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22 °C
- Humidity (%): 64 to 66 % (relative)
- Air changes (per hr): 12 to 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours of light and 12 hours of dark

IN-LIFE DATES: From: 20 April 2012 To: 30 April 2012

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
The test material was made into a paste with Milli-Q water
Controls:
other: The adjacent untreated skin of each animal served as the control site.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): The test material was made into a paste by moistening with 0.6 mL of Milli-Q water.
Duration of treatment / exposure:
Initial animal: 3 minutes, 1 hour and 4 hours of contact; Two additional animals: 4 hours of contact

The rabbits were exposed in a stepwise manner (1+2 rabbits). The initial animal was tested with 3 test patches (3 minutes, 1 hour and 4 hours of contact). The patches were removed after 3 minutes, 1 hour, or 4 hours of skin contact. All test sites were evaluated for corrosion 30 to 60 minutes after patch removal. A subsequent evaluation was performed approximately 24 hours after removal of the four-hour patch. Since corrosion was not observed at any of the test sites, two additional rabbits were exposed to the test material with one patch only for 4 hours.
Observation period:
72 hours
Number of animals:
3 male animals
Details on study design:
TEST SITE
- Area of exposure: An approximately 6 cm² intact test site was selected on each animal on the left dorsolateral trunk surface. Approximately 24 hours before treatment, the fur (about 14 x 19 cm) was clipped with an electric clipper and care taken to avoid abrading the skin. After clipping and prior to application, the test site was checked for any abnormalities according to the “Primary Skin Irritation Scoring System”; all the test sites were found to be normal.
- Type of wrap if used: The test material paste was applied on 6 ply gauze pad (2 x 3 cm). The entire trunk of each animal was then wrapped with non-irritating semi-occlusive adhesive tape to avoid dislocation of the patch. Each rabbit was restrained using an Elizabethan collar for 24 hours post application of the test patch.

SCORING SYSTEM:
The test sites were examined for signs of erythema and oedema within 60 minutes and at intervals of approximately 24, 48 and 72 hours after test patch removal according to the "Primary Skin Irritation Scoring System" developed by Draize, et al. (1944).

OBSERVATIONS
- Clinical Observations: The rabbits were observed for clinical signs of toxicity and mortality 4 times (at hourly intervals) on the day of test material application and once daily thereafter until the end of the observation period.
- Body Weights: Body weights were recorded at the start of acclimatisation, day 1 of treatment (just before test material application) and at termination of observation.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The erythema score was 0 at every time point for each animal
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean score at 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: The oedema score was 0 at every time point for each animal
Irritant / corrosive response data:
There were no skin reactions observed in all three rabbits at 1, 24, 48 and 72 hours post removal of the 4-hour test patch.
Other effects:
There were no clinical signs of toxicity observed, and none of the animals died, during the course of the study.
The body weight of all three rabbits increased throughout the observation period. See Table 1.

Any other information on results incl. tables

Table 1: Body Weight

Rabbit Number

Body weight (kg)

At start of acclimatisation

At treatment

At termination

RB9609

2.48

2.59

2.68

RB9610

2.68

2.78

2.81

RB9611

2.70

2.82

2.88

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the test material caused no irritation to the skin of male New Zealand White rabbits and requires no classification in accordance with EU criteria.
Executive summary:

The potential of the test material to cause skin irritation/corrosion to the skin of male New Zealand White rabbits was assessed in accordance with the standardised guidelines OECD 404 and US EPA OPPTS 870.2500 under GLP conditions.

The study was conducted in a stepwise manner (i.e., one rabbit was dosed, followed by two additional rabbits); initially one rabbit was tested to determine the irritation/corrosion potential of the test material. Three test patches were applied.

For each patch, 0.5 g of the test material as a paste in Milli-Q water was applied to the clipped, intact skin in a semi-occlusive fashion. The patches were removed after 3 minutes, 1 hour or 4 hours of skin contact. All test sites were evaluated for corrosion one hour after patch removal.

A subsequent evaluation was performed approximately 24 hours after removal of the four-hour patch. All test sites were also evaluated for skin irritation according to the Draize (1944) evaluation method.

As corrosion was not observed at any of the test sites in the first animal tested, two additional rabbits were tested, each with a single patch for a 4-hour exposure period only.

The degree of irritation was evaluated and scored according to the Draize (1944) scale at 1, 24, 48 and 72 hours following removal of the test patch.

There were no clinical signs of toxicity or mortality and all animals gained weight. Neither erythema nor oedema was noted during the observation period under the conditions of the study.

Under the conditions of this study, the test material caused no irritation to the skin of male New Zealand White rabbits and requires no classification in accordance with EU criteria.