Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Report date: 16 December 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test item is not indicated.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Report date: 16 December 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test item is not indicated.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing, 24 hours for duration of treatment, only 72 hours of observation period
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
other: New Zealand
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.5 to 3.5 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
No data are available.

IN-LIFE DATES: From: 20 November 1980 To: 23 November 1980
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
Concentration: 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: disc of 3 cm diameter
- % coverage: no data
- Type of wrap if used: adhesive tape and pansement

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

OBSERVATION TIME POINTS
25 hours (= 1 hour after removal of the tape) and 72 hours after application

SCORING SYSTEM:
* Erythema and eschar formation:
No erythema = 0
Very slight erythema (barely perceptible) = 1
Slight erythema (perceptible) = 2
Moderate to severe erythema = 3
Severe erythema and with eschar formation:
* slight eschar = 4
* extended eschar (more than 50% of the surface application) = 8

* Oedema formation:
No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edges of area well-defined by definite raising) = 2
Moderate oedema (raised approximately 1 millimetre) = 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) = 4

The numerical rating scale above allows the determination of a "Primary Skin Irritation Index"; this index is equal to the sum of the individual values which express the intensity of the erythema and the intensity of the edema, 25 hours and 72 hours after the application, both on the intact skin and on the scarified skin, divided by 16 (number of treated rabbits x 4). The maximum value of the primary skin irritation index is 12.

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 25 and 72 hours
Score:
8.63
Reversibility:
not specified
Irritant / corrosive response data:
All animals presented a well visible erythema exceeding the application area at time 25 hours.
- Normal area:
All animals presented oedema and erythema (scored 3, 4 or 8) at time 25 and 72 hours. One rabbit presented an extended eschar at time 25 hours and a very important necrosis at time 72 hours.

- Scarified area:
All animals presented oedema and erythema (scored 3, 4 or 8) at time 25 and 72 hours. One rabbit presented a very important necrosis at time 72 hours.

Table 2: Results

Evaluation of irritation

Rabbits n°

Areas

25 hours

72 hours

Total

Erythema

Oedema

Total

Erythema

Oedema

Total

(25 + 72h)

Er. + oed.

585

normal

4*

4

8

G4

3

7

15

scarified

4*

4

8

G4

3

7

15

586

normal

4

4

8

G4

4

8

16

scarified

4*

4

8

G4

4

8

16

587

normal

4*

4

8

G4*

4

8

16

scarified

4*

4

8

G4*

4

8

16

585

normal

8

4

12

8+

4

12

24

scarified

4

4

8

8+

4

12

20

*: Erythema without eschar

G: Skin of greyish appearance on a zone superior to that of the application

+: Very important necrosis with bleeding well beyond the area of the application

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In these test conditions, Thrichloroacetyl chloride is considered as corrosive to skin.
Executive summary:

A skin irritation study was performed with Trichloroacetyl chloride (TCAC) in rabbits. The method followed was similar to the OECD Guideline 404 and the study was not performed in accordance with GLP. TCAC was applied on scarified or normal skin for 24 hours under occlusive coverage. Examinations were performed at 25 hours (1 hour after removal of the tape) and 72 hours after application. Erythema (and eschar) and oedema formation were scored. All animals presented a well visible erythema exceeding the application area at time 25 hours. All animals presented oedema and erythema (scored 3, 4 or 8) at time 25 and 72 hours. One rabbit presented a very important necrosis at time 72 hours.

TCAC is classified corrosive to skin according to the UN GHS and CLP criteria.

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
4 animals, observation period of 7 days
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:

Name of the test material in the report: Chlorure de trichloracetyle

Test animals / tissue source

Species:
rabbit
Strain:
other: New Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.0 to 3.0 kg
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
No data are available.

IN-LIFE DATES: From: 27 November 1980 To: 4 December 1980

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye, which remained untreated, served as control
Amount / concentration applied:
Amount applied: 0.1 mL introduced into the conjunctival sac of the left eye
Duration of treatment / exposure:
Single conjunctival instillation
Observation period (in vivo):
1 hour and 1, 2, 3, 4 and 7 days after the administration
Number of animals or in vitro replicates:
4 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM:
Conjonctivae
A = chemosis (oedema)
- none = 0
- slight = 1
- pronounced, with eversion of the eyelids = 2
- with half-closed eyelids = 3
- with closed or almost closed eyelids = 4

B = lacrimal secretions
- none = 0
- slight = 1
- with moistening of the hairs around the eyelids = 2
- same observation, but on large surfaces around the eye = 3

C = redness of the palpebral conjunctiva
- normal appearance = 0
- vessels significantly more injected than normal = 1
- diffuse redness with vessels difficult to individualize = 2
- color dark red diffuse = 3

Iris
A1 = damage of this iris
- normal appearance = 0
- aspect much more pleated than normal, congestion, swelling, circumcorneal injections (or only one of these manifestations), but iris still reacting to light (even weakly or slowly) = 1
- no reaction to light, hemorrhage, significant destruction (or only one of these manifestations) = 2

A2 = degree of opacity
- normal appearance = 0
- loss of shine or polish, but clearly visible iris details = 1
- translucent area, with slightly obscured iris details = 2
- opalescent area, with invisible iris details and barely visible pupil contour = 3
- iris and pupil invisible = 4

B2 = surface of the opacity
- less than or equal to a quarter (but not zero) = 1
- between one-quarter and one-half = 2
- between one-half and three quarters = 3
- more than three quarters = 4

The coefficients of the conjunctival damage, the iris damage and the corneal damage allow to determine 3 indices of ocular irritation:
- the individual eye irritation index (= IEI), the maximum value of which equals 110, is equal to eacg time, for each rabbit, to
2 (A + B + C) + 5A1 + 5A2B2
- the mean ocular irritation index (= MOI) is the average, at each time, of the IEI of the 4 treated rabbits;
- the acute eye irritation index (= AEI) is the highest MOI obtained within 7 days of observation.

The interpretation of the results is made from these 3 index and is drawn from KAY and CALANDRA (J. Soc. Cosmet. Chem., 13, 281 (1962): "Interpretation of eye-irritation tests").









Results and discussion

Results of in vivo studyopen allclose all
Irritation parameter:
other: Mean ocular irritation score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Remarks:
importance of the effects
Irritation parameter:
other: Mean ocular irritation score
Basis:
mean
Time point:
7 d
Score:
90.67
Reversibility:
not reversible
Irritant / corrosive response data:
The importance of injuries did not allow calculating mean scores for chemosis, corneal opacity and iritis.
Observations: Conjunctival chemosis (grade 4) were observed in all  animals at 1h and remained present at the end of the observation study (day 7). Corneal opacity was observed in all of the animals and remained  present at day 1 and day 2 to day 7 the observation of corneal opacity was impossible because of severe chemosis. One rabbit presented a necrose on day 7.

Any other information on results incl. tables

Table 1: Results

Evaluation of effects

1 hour

Day 1

Day 2

N° of rabbits

757

758

759

760

757

758

759

760

757

758

759

760

Conjunctiva

A) Chemosis

0 - 4

4

4

4

4

4

4

4

4

4

4

4

4

B) Discharge

0 - 3

1

1

1

1

2

2

2

2

2

2

2

2

C) Enanthema

0 - 3

?

?

?

?

?

?

?

?

?

?

?

?

(A+B+C) x 2

(max. = 20)

≥ 10

≥ 10

≥ 10

≥ 10

≥ 12

≥ 12

≥ 12

≥ 12

≥ 12

≥ 12

≥ 12

≥ 12

 

Direct photomotor reflex of pupil (§)

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

¥

¥

¥

¥

Iris

Congestion

0 – 2

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

¥

¥

¥

¥

x 5

(max. = 10)

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

ɸ

¥

¥

¥

¥

(§) N = Normal – R = Reduced – No reflex

Cornea

A) Opacity

0 – 4

4

4

4

4

4

4

4

4

¥

¥

¥

¥

B) Area affected

1 – 4

α

α

α

α

α

α

α

α

¥

¥

¥

¥

A x B x 5

(max. = 80)

α

α

α

α

α

α

α

α

¥

¥

¥

¥

 

Individual ocular irritation score IEI

(max. 110)

/

/

/

/

/

/

/

/

/

/

/

/

Observations:

?: the palpebral conjunctiva presented a blackish appearance not allowing the observation of the enanthema.

ɸ: the degree of corneal opacification did not allow observation of the iris.

α: the degree of chemosis allowed the observation of only a small part of the corneal surface; only the degree of opacification could be estimated.

¥: the degree of chemosis made reading impossible.

/: the significance of the damages does not allow calculating a value for this index.

Mean score per zone

Conj. + Iris + Corn.

Conj. + Iris + Corn.

Conj. + Iris + Corn.

≥ 10.00

/

/

≥ 12.00

/

/

≥ 12.00

/

/

Mean ocular irritation score MOI

Standard deviation S

 

/

 

/

 

/

 

Evaluation of effects

Day 3

Day 4

Day 7

N° of rabbits

757

758

759

760

757

758

759

760

757

758

759

760

Conjunctiva

A) Chemosis

0 - 4

4

4

4

4

4

4

4

4

4

4

4

4

B) Discharge

0 - 3

2

2

2

2

1

2

2

2

1

1

2

2

C) Enanthema

0 - 3

?

?

?

?

¥

¥

¥

¥

¥

¥

¥

¥

(A+B+C) x 2

(max. = 20)

≥ 12

≥ 12

≥ 12

≥ 12

≥ 10

≥ 12

≥ 12

≥ 12

≥ 10

≥ 10

≥ 12

≥ 12

 

Direct photomotor reflex of pupil (§)

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

Ӿ

Iris

Congestion

0 – 2

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

Ӿ

x 5

(max. = 10)

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

¥

Ӿ

(§) N = Normal – R = Reduced – No reflex

Cornea

A) Opacity

0 – 4

¥

¥

¥

¥

¥

¥

¥

¥

4+

4+

4+

Ӿ

B) Area affected

1 – 4

¥

¥

¥

¥

¥

¥

¥

¥

4

4

4

Ӿ

A x B x 5

(max. = 80)

¥

¥

¥

¥

¥

¥

¥

¥

80

80

80

Ӿ

 

Individual ocular irritation score IEI

(max. 110)

/

/

/

/

/

/

/

/

≥ 90

≥ 90

≥ 92

/

Observations:

?: the palpebral conjunctiva presented a blackish appearance not allowing the observation of the enanthema.

¥: the degree of chemosis made reading impossible.

+: the degree and the surface of corneal opacification were determined after the sacrifice of the animal.

Ӿ: at the opening of the eyelids, total necrosis of the treated eye was observed.

/: the significance of the damages does not allow calculating a value for this index.

Mean score per zone

Conj. + Iris + Corn.

Conj. + Iris + Corn.

Conj. + Iris + Corn.

≥ 12.00

/

/

≥ 11.50

/

/

≥ 10.67

/

80.00

Mean ocular irritation score MOI

Standard deviation S

 

/

 

/

 

≥ 90.67

1.15

                                                                                                                                            Mean calculated on 3 rabbits

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the test conditions, Trichloroacetyl chloride is considered as highly irritant.
Executive summary:

An eye irritation study was performed with Trichloroacetyl chloride (TCAC) in rabbits. The method followed was similar to the OECD Guideline 405 and the study was not performed in accordance with GLP. A single dose of TCAC in its originak form was introduced into the conjunctival sac of the left eye. The right eye was not treated and served as control. The eyes were not rinsed after administration of TCAC.

Ocular reactions were observed 1 hour and 1, 2, 3, 4 and 7 days after the administration.

The importance of injuries did not allow calculating mean scores for chemosis, corneal opacity and iritis.

Conjunctival chemosis (grade 4) were observed in all  animals at 1h and remained present at the end of the observation study (day 7). Corneal opacity was observed in all of the animals and remained  present at day 1 and day 2 to day 7 the observation of corneal opacity was impossible because of severe chemosis. One rabbit presented a necrose on day 7.

TCAC is classified corrosive to eyes according to the UN GHS and CLP criteria.