Registration Dossier

Administrative data

Endpoint:
eye 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 eye irritation according to the U.S. Consumer Product Safety Commission, Code of federal regulations, tItle 16, section 1500.42 (test for eye irritants). Although GLP standards were not specified, many details were given concerning materials and methodology as well as results and interpretation of data. Hence the study should be considered a Klimisch 2.b, a guideline study with acceptable restrictions.

Data source

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

Materials and methods

Principles of method if other than guideline:
Code of Federal Regulations, Title 16, Section 1500.42
Updated as "1500.42 Test for eye irritants" (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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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
- Sex: male

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

No more data available

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: right eye is used for testing, left eye is control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µL

No more data available
Duration of treatment / exposure:
No data
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
Six male albino rabbits
Details on study design:
SCORING SYSTEM:
Pathological symptoms were checked in the cornea (i.e. degree of opacity and area of opacity), iris and conjunctivae (i.e. redness, chemosis and "ausflub"). This was done according to a scoring system taken from "The appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p.51). This scoring system is similar to the grading procedure from the OECD guideline 405, except that in the latter opacity is not subdivided and for conjunctiva only redness and chemosis are considered.


TOOL USED TO ASSESS SCORE: The eyes are checked during the test using an ophthalmoscope. After 8 days the cornea is examined after applying fluorescein (1 drop of fluoresceine in opthalmic solution directly on the cornea. After washing with physiological salt water injured areas of the cornea appear yellow green under UV light)


No more data available

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h
Score:
5.8
Max. score:
80
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48h
Score:
5
Max. score:
80
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72h
Score:
5
Max. score:
80
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h, 48h and 72h combined
Score:
5.3
Max. score:
80
Reversibility:
fully reversible
Remarks:
after 8 days
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24h, 48h and 72h combined
Score:
0
Max. score:
10
Remarks on result:
other: No effect of test substance observed, detailed overview of results in remark section
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24h
Score:
9
Max. score:
20
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48h
Score:
9.3
Max. score:
20
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72h
Score:
10
Max. score:
20
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24h, 48h and 72h combined
Score:
9.4
Max. score:
20
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24h
Score:
14.8
Max. score:
110
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48h
Score:
14.3
Max. score:
110
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72h
Score:
15
Max. score:
110
Remarks on result:
other: Detailed overview of results in remark section
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24h, 48h and 72h combined
Score:
14.7
Max. score:
110
Irritant / corrosive response data:
- Raw data for each individual animal at each observation time is given in the section "Remarks on results including tables and figures"

- Calculation of maximum value:
Cornea: subdivided in degree of opacity and area of opacity, each having a maximum score of 4. The maximum score for the cornea observation equals "degree of opacity" x "area of opacity" x 5 (i.e. maximum score of 80).
Iris: maximum score of 2, which is multiplied by 5. Thus the maximum score for the iris is 10.
Conjunctivae: subdivided in redness, chemosis and "ausflub" which have as maximum score 3, 4 and 3 respectively. The maximum score for the conjunctivae in total equals the sum of the three subdivisions multiplied by 2 (i.e. 20)
Overall irritation score: sum of scores obtained for cornea, iris and conjunctivae. Hence the maximum to be obtained is 110
Other effects:
No data

Any other information on results incl. tables

- The slight irritation has practically disappeared after 8 days.

- Table presenting the raw data of the test:

24h 48h 72h After 8d
N° of test rabbit 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6 1 2 3 4 5 6
Cornea
A) Opacity 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0
B) Area 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0
a=AxBx5 (Max. 80) 5 5 5 10 5 5 5 5 5 5 5 5 5 5 5 5 5 5
Iris (A) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
b=Ax5 (Max. 10) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Conjunctivae
A) Redness 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 1 1 1 1
B) Swelling 2 2 1 2 2 2 2 2 1 1 2 2 2 2 1 1 2 2 2 2 1 1 2 2
C) Ausfluβ 1 1 0 1 1 1 1 1 0 1 2 1 2 1 1 1 2 1 1 0 0 1 0 0
c=(A+B+C)x2(Max. 20) 10 10 4 10 10 10 10 10 6 8 12 10 12 10 8 8 12 10
Sum of a, b and c (Max. 110.0) 15 15 9 20 15 15 15 15 11 13 17 15 17 15 13 13 17 15

- Mean overall irritation score:

sum of individual overall irritation scores divided by 18 (i.e. 6 animals and 3 time points, 24, 48 and 72h). Thus the mean overall irritation score equals 256/18 = 14.7

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The authors tested eye irritation as a result of 4-chloro-benzotrichloride exposure according to the U.S. Consumer Product Safety Commission, Code of federal regulations, title 16, section 1500.42 (test for eye irritants). Under the test conditions, a mean overall irritation score of 14.7 was found. Using the classification described in the study report, the test substance should be considered as slightly irritating.

However according to the harmonized CLP classification N° 1272/2008 and the ECHA guidance on CLP criteria, the test substance is not classified at present.
Executive summary:

The authors tested eye irritation as a result of exposure to 4-chloro-benzotrichloride (CAS n° 5216-25-1) according to the U.S. Consumer Product Safety Commission, Code of federal regulations, title 16, section 1500.42 (test for eye irritants). The right eye of six white New Zealand Albino rabbits was exposed to the test substance, while the left eye was used as control. Eyes were checked after 24h, 48h and 72h of exposure using a ophthalmoscope. A final check was done after 8 days and slight irritation had practically disappeared.

Under the test conditions a mean overall irritation score of 14.7 was found, which results in a classification of the test substance as slightly irritating according to the classification described in the study report.

However according to the harmonized CLP classification N° 1272/2008 and the ECHA guidance on CLP criteria, the test substance is not classified at present.

GLP standards were not specified. The test was perfomed according to the methodology mentionned above and many details were given concerning materials and methodology as well as results and interpretation of data. Hence the study should be considered a Klimisch 2.b.