Registration Dossier

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD 404 guideline; under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chloro-o-xylene
EC Number:
210-438-6
EC Name:
4-chloro-o-xylene
Cas Number:
615-60-1
Molecular formula:
C8H9Cl
IUPAC Name:
4-chloro-1,2-dimethylbenzene
Details on test material:
- Name of test material (as cited in study report): 4-chloro-o-xylene
- Physical state: Liquid
- Storage condition of test material: Room temperature, keep dry
- Other: Stable under recommended conditions of storage and handling.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: 10 weeks
- Weight at study initiation: 2.12 - 2.19 kg
- Housing: Individually housed in suspended stainless steel cages.
- Diet (e.g. ad libitum): TEK 8630 Rabbit Diet, Harlan Teklad, Madison, WI, ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: Miniumum of 5 days under the same confitions as for the actual test.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 +/- 5
- Humidity (%): 30-70
- Air changes (per hr): 10 - 15

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin areas of the test animal serve as the control.
Amount / concentration applied:
Test material was applied directly to the skin of rabbits as supplied by the sponsor. A dose of 0.5ml was applied to each application site.
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
Screening procedure:
Animals selected for this study were examined to ensure their skin was free from irritation, trauma and disease.

Preparation of test animals:
24 hours before application of the test substance, the application sites were prepared by clipping the skin of the trunk free of hair. These application sites were not abraded intentionally or accidentally during preparation. Approximately 10% of the body surface was clear for application of the test substance.

Test substance application:
Test material was applied to a small area of skin (approx. 6 sq.cm). At each application area, a gauze patch was held in place with non-irritating tape. This patch was loosely held in contact with the skin for the duration of the exposure period. Care was taken to prevent access by the animal to the patch, which could result in accidental ingestion/inhalationof the test material.

Initial test:
It was thought that the test material could cause severe irritancy or corrosion and so a single animal was used to begin with. Three test patches were applied simultaneously to this animal. The first patch was removed after 3 minutes, the second patch is removed after 1 hour and the third patch removed at 4 hours (provided no corrossion is seen at three minutes or 1 hour in which case the test would be immediately terminated). If no corrosive effect is observed, a confirmatory test with 2 additional animals is used with a single patch applied for an exposure period of 4 hours.

After the four hour exposure period, animals were examined for signs of erythema and oedema at 60 minutes, then 24, 48 and 72 hours after patch removal. Further observations were recorded to determine the nature and reversibility of the responses noted.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 60 minutes
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Day 4
Score:
1.67
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Day 5
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Day 6
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Day 7-14
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 60 minutes
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Day 4
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Day 5
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Day 6
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Day 7-14
Score:
0
Max. score:
4
Irritant / corrosive response data:
In the initial test no signs of erythema or edema were observed after 3 minutes, 1 hour or 1 hour after 4 hours of exposure. Slight erythema were and oedema were observed after 24 hours. Slight erythema and well-defined edema were noted at the 48 and 72 hour observation.

In the confirmatory test, the additional animals showed no signs of erythema or edema at 60 minutes post patch removal. One rabbit was observed to have no signs of erythema but slight edema at the 24 hour observation point, whereas the other rabbit showed slight erythema and edema. Both rabbits showed slight erythma and edema at the 48 hour observation which elevated to well-defined erythema by the 72 hour observation period.

All 3 rabbits exhibited slight to well-defined signs of erythema and edema by day 4, but receded in the following days. The skin at the test site in all 3 animals was noted to be dry and scaly. All observations of erythema and edema were reversed by day 7 in two rabbits and by day 8 in the third rabbit. The skin at the test site in all three animals was noted to be dry and scaly that spread beyond the test application sites into the control areas. Dry scaly skin persisted to day 14.

None of the control sites of any animal at any of the observation periods showed signs of erythema or edema.
Other effects:
Other than signs of erythema and edema, no other signs of toxicity were observed.

Any other information on results incl. tables

Animal Test Sites / Control Sites
Hours Days
1* 24 48 72 4 5 6 7 8 9 10 11 12 13 14
  ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED ER OED
1 0/0 0/0 1/0 1/0 1/0 2/0 1/0 2/0 1/0 2#/0 1/0 2#/0 0/0 1#/0 0/0 0#/0 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^
2 0/0 0/0 0/0 1/0 1/0 1/0 2/0 1/0 2/0 2/0 1/0 2#/0 0/0 1#/0 0/0 0#/0 0/0 0#/0 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^
3 0/0 0/0 1/0 1/0 1/0 1/0 2/0 1/0 2/0 2#/0 1/0 2#/0 0/0 1#/0 0/0 0#/0 0/0 0#/0 0/0 0#/0 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^ 0/0 0^/0^

ER = Erythema

OED = Oedema

# Patches of white, hard, scaly skin, confined to area substance application.

^ Hard scaly skin spread beyond confines of application, control sites (untreated skin) is now affected.

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 was considered by the report author to be a slight irritant to New Zealand White rabbit skin, though this was not severe enough to warrant classification in accordance with EU criteria.
Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The study was performed to GLP and the method was designed to meet the requirements of OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion”.

The test substance was evaluated in 3 young New Zealand white rabbits. A dose of 0.5 ml of test substance was applied to the intact shorn dorsal skin site under a semi-occlusive dressing for 4 hours. The patch was then removed and skin observations were made 1, 24, 48 and 72 hours after patch removal; observations continued up to 14 days post-exposure. A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced slight to well-defined erythema and edema by day 4. All observations of erythema and edema were reversed by day 7 in two rabbits and day 8 in the third rabbit. The skin at the test site in all 3 animals was dry and scaly. No corrosive effects were noted. The test material was considered by the report author to be a slight irritant to New Zealand White rabbit skin, though this was not severe enough to warrant classification in accordance with EU criteria.