Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The authors tested primary skin irritation according to the U.S. Consumer Product Safety Commission, Code of federal regulations, tItle 16, section 1500.41 (patch test in rabbits). Although GLP standards were not specified, many details were given concerning materials and methods as well as results and interpretation of data. Hence the study should be considered a Klimisch 2.b, guideline study with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1980

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Code of Federal Regulations, Title 16, Section 1500.4
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
abraded skin included, 24 hours exposure instead of 4 hours, reading point at 24 hours and 72 hours after the end of exposure missing, and 8 days post exposure observation period
Principles of method if other than guideline:
Patch test in rabbits described in "Code of Federal Regulations, Title 16, Section 1500.41"
Updated as "1500.41 Method of testing primary irritant substances" (2009 edition of 16 CFR Ch. II, Consumer Product Safety Commission)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): p-Chlorbenzotrichlorid 99
- Physical state: liquid

No more data available

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: "Lippischen" test animal brood/Extertal 1
- Weight at study initiation: 2.1 kg
- Housing: individually housed
- Diet (e.g. ad libitum): ad libitum (mümmel z; ssniff/Soest)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 - 14 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18°C
- Humidity (%): 40%
- Photoperiod (hrs dark / hrs light): 12h light/12h dark

No further data available

Test system

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded skin (clipped free of hair)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 µl

No more data available
Duration of treatment / exposure:
24h
Observation period:
Total of 8 days with evaluation of reaction after 24h of exposure (i.e. removal of patch), 48h and 72h (i.e. 48h after first reading)
Number of animals:
Six male rabbits
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: elastic bandage
- Area preparation for exposure: an area of ca. 8 x 8 cm on both sides of the trunk was shaved 24h before the start of the test using electic clippers. IOn the left side of the trunk the skin remained intact, but the right side was abraded. Area of skin was previously abraded.


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24h


SCORING SYSTEM for skin reaction only for timepoints 24h and 72h:
- Erythema and eschar formation (maximum value possible is 4):
No erythema ............................................................................................................................. 0
Very slight erythema (barely perceptible) ............................................................................ 1
Well-defined erythema ............................................................................................................ 2
Moderate to severe erythema ................................................................................................ 3
Severe erythema (beet redness) to slight eschar formations (injuries in depth) .......... 4

- Edema formation (maximum value possible is 4):
No edema ....................................................................................................................................................... 0
Very slight edema (barely perceptible) ...................................................................................................... 1
Slight edema (edges of area well defined by definite raising) ............................................................... 2
Moderate edema (raised approximately 1 millimeter) ............................................................................ 3
Severe edema (raised more than 1 millimeter and extending beyond the area of exposure) ......... 4


No further data available

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
>= 3.3
Max. score:
8
Reversibility:
no data
Irritant / corrosive response data:
- All irritant response data are given in Table 1 (in remarks on results including tables and figures)

- Method of calculating the maximum score for the primary dermal irritation index given in the results table:
The max score for the primary dermal irritation index = (sum of maximum evaluation values)/4. There are eight evaluation values (i.e. erythema after 24 and 72h for both intact and abraded skin and edema after 24 and 72h for both intact and abraded skin) each having a maximum value of 4. Thus maximum primary dermal irritation score = 8
Other effects:
No data

Any other information on results incl. tables

- Table 1: Overview of skin reaction (i.e. erythema and edema) after 24h, 72h and 8d for intact and abraded skin of male white New Zealand rabbits since start of exposure to 4 -chloro-benzotrichlorid. The values after 48h are not given.

Time Animal n° Sum of evalution values (24 and 72h) Average evaluation value
1 2 3 4 5 6
Erythema and eschar Intact 24h * * * * * * - -
72h * * * * * * - -
8d * * * * * *
Abraded 24h * * * * * * - -
72h * * * * * * - -
8d * * * * * *
Edema Intact 24h 4 4 3 3 4 4 22 3.67
72h 3 4 4 3 3 3 20 3.33
8d 4 4 4 4 4 4
Abraded 24h 3 3 4 3 3 4 20 3.33
72h 3 3 4 2 2 4 18 3.00
8d 4 4 4 3 4 4

* Paleness of the skin was observed within 24h with development of superficial, whitish corrosive crusts (above the treated surface). After 8d the skin dried out and became slightly brown discoloured.

- Calculation of primary irritation score:

Primary irritation score = (sum of average evaluation values)/4, thus primary irritation score >= 3.3*

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The authors tested primary skin irritation of 4-chloro-benzotrichloride according to the U.S. Consumer Product Safety Commission, Code of federal regulations, title 16, section 1500.41 (patch test in rabbits). Under these test conditions the primary irritation index has been estimated superior to 3.3 (with only oedema results) and taken into account the results for erythema, the 4-chloro-benzotrichloride should be considered corrosive according to the guideline 16CFR1500.41. Classification according to the CLP regulation n° 1272/2008 EC and with the help of the ECHA guidance on CLP criteria would lead to consider 4-chlorobenzotrichloride as a skin irritant category 2, as the mean score for edema for intact skin at 24 and 72 hours is higher than 2.3 and less than 4 in more than four rabbits on six.
Executive summary:

The authors tested primary skin irritation of 4-chloro-benzotrichloride (CAS n° 5216-25-1) according to the U.S. Consumer Product Safety Commission, Code of federal regulations, title 16, section 1500.41 (patch test in rabbits). The skin (left test site intact and right site abraded covered with occlusive gauze) of six white New Zealand Albino rabbits was checked after 24h of exposure, 48h and 72h (i.e. 24h and 48h respectively after removal of patch with test substance). A final check was done after 8 days.

Paleness of the skin was observed within 24h with development of superficial, whitish corrosive crusts (above the treated surface). After 8d the skin was dry and had become slightly brown discoloured. For intact skin after 24h and 72h and abraded skin after 24h the evaluation value for edema indicated moderate to high irritation. For abraded skin after 24h the evaluation value for edema indicated moderate to high irritation, while for 72h the average value represented moderate irritation. After 8 days the evaluation value for edema was 4 (i.e. high irritation) for all test sites except one, which scored 3. The experiment stopped at this point. The primary irritation index was estimated to be over 3.3 taking into account the results for oedema. In front of such evidences, 4 -chlorobenzotrichloride should be considered as a potential skin irritant for rabbits.

Considering the erythema data, the authors considered that the test substance should be considered corrosive according to the guideline followed. However, Classification according to the CLP regulation n° 1272/2008 EC and with the help of the ECHA guidance on CLP criteria would lead to consider 4-chlorobenzotrichloride as a skin irritant category 2, as the mean score for edema for intact skin at 24 and 72 hours is higher than 2.3 and less than 4 in more than four rabbits on six.

GLP standards were not specified for this experiment. The test was perfomed according to the guideline 16CFR1500.41 and many details were given concerning materials and methods as well as results and interpretation of data. Hence the study should be considered as reliable with restrictions, a klimisch 2.b study, a guideline study with acceptable restrictions.