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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
/ Basic data given.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
/ Basic data given.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation:
- Weight at study initiation:
200 - 300 g
- Fasting period before study:
animals were fasted overnight
- Diet: approprtiate commercial diet, ad libitum
- Water: municipal water, ad libitum
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10% (w/v)
- Justification for choice of vehicle: The substance was not suspending in water
Doses:
125, 250, 500 and 1000 mg/kg bw (males)
125, 250 and 500 mg/kg bw (females)
No. of animals per sex per dose:
5
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, Day 7 and Day 14 (prior to sacrifice)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathologic evaluation
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
308 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 values are calculated by the moving average method (Thompson 1947) and are based on a 14-day observation period.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
406 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 values are calculated by the moving average method (Thompson 1947) and are based on a 14-day observation period.
Mortality:
females: 3/5 animals died on Day 5, 1/5 animals on Day 6 and 1/5 animals on Day 8 at a concentration of 500 mg/kg bw; 1/5 animals died on Day 5 at 250 mg/kg bw and no animal died at 125 mg/kg bw.

males: 1/5 animals died on Day 3, 1/5 animals on Day 4, 2/5 animals on Day 5 and 1/5 animals on Day 6 at a concentration of 1000 mg/kg bw; 1/5 animals died on Day 5, 1/5 animals on Day 8 and 1/5 animals on Day 14 at a concentration of 500 mg/kg bw; 1/5 animals died on Day 6 at 250 mg/kg bw and no animal died at 125 mg/kg bw.
Clinical signs:
females: At a test substance concentration of 500 mg/kg/bw sluggishness, unkempt appearance, red crust on perinasal and periocular fur was observed at Day 4, swollen eyelids and kyphosis at Day 5. At a test substance concentration of 250 mg/kg/bw sluggishness, unkempt appearance, red crust on perinasal and periocular fur was observed at Day 3, emaciation and intermittent tremors in 1 animal at Day 7 and alopecia and unkempt appearance at Day 14. No clinical signs were observed at the lowest test substance concentration.

males: At a test substance concentration of 1000 mg/kg/bw sluggishness and yellow periurogenital discharge was observed at Day 1, unkempt appearance in 2 animals at Day 1, swollen eyelids (eyes partially closed), red perinasal and periocular discharge and kyphosis at Day 3, intermittent tremors and emaciation at Day 4. At a test substance concentration of 500 mg/kg/bw red perinasal crust was observed at Day 2, sluggishness, swollen eyelids, kyphosis and red periocular crust at Day 3, unkempt appearance and emaciation at Day 4, lacrimation in 2 animals at Day 5, intermittent tremors in 2 animals at Day 7 alopecia in 1 animal at Day 5. Recovery of 1 survivor at Day 9. At a test substance concentration of 250 mg/kg/bw red perinasal crust was observed at Day 2, sluggishness and swollen eyelids at Day 3, unkempt appearance and emaciation at Day 4. At a test substance concentration of 125 mg/kg bw unkempt appearance was observed in 2 animals at Day 5. Recovery was observed at Day 7.
Body weight:
All animals showed normal body weight gains during the observation period.
Gross pathology:
females: Lungs mottled light and dark red at a test substance concentration of 500 mg/kg bw. At 250 mg/kg bw, 1/5 females (the one which died later) showed red encrustation of perinasal and periocular fur while in the other 4 animals nothing remarkable was observed. At 125 mg/kg bw no gross pathological abnormalities were observed.
males: Lungs mottled light and dark red at a test substance concentration of 1000 mg/kg bw. At 500 mg/kg bw lungs of 3/5 females (the ones which died later) were dark red and the thoracic and abdominal cavity of 1 animal was filled with brown liquid. In the other 2 animals, nothing remarkable was observed. At 250 mg/kg bw, 1/5 males (the one which died later) showed nothing remarkable, while the cervical lymph nodes of 2/5 animals were enlarged. At 125 mg/kg bw, the spleen of 1/5 animals was enlarged.

Table 1: Mortality and body weight changes

 

Dose
[mg/ kg bw]

Dead/ Dosed animals

Days of death

Body weight change

Day 7
(range (mean) [g] )

Day 14
(range (mean) [g] )

Male

1000

5/5

3, 4, 5, 5, 6

-

-

500

3/5

5, 8, 14

-38 - 9 (-18)

-2 - 42 (20)

250

1/5

6

2 - 19 (8)

61 - 92 (78)

125

0/5

3, 4, 5, 5, 6

30 - 49 (38)

87 - 120 (111)

Female

500

5/5

5, 5, 5, 6, 8

173

-

250

1/5

5

2 - 19 (10)

22 - 58 (38)

125

0/5

-

-10 - 33 (5)

40 - 60 (47)

Interpretation of results:
other: CLP/ EU GHS criteria met, classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: Acute oral toxicity, Cat. 4, H302
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1985
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
No information available about the tested concentration.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Inhalation of substantially saturated vapor, single exposure for 6 hours, static conditions 25 °C
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation:
200 - 300 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
25
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The vapour was produced by enclosing the test substance in a sealed animal chamber for 18 h (static conditions). Oxygen was added as needed in order to maintain a chamber oxygen content of approximatively 20%
- Exposure chamber volume: 120 L
- Temperature in air chamber: 25 °C
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
substantially saturated vapor
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weighing was performed in the beginning and on Day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LC50
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality was observed during the observation period.
Clinical signs:
No clinical signs were observed.
Body weight:
All animals showed normal body weight gains during the observation period. (in males: mean body weight gain of 68 g and 120 g after 7 and 14 days, respectively; in females: mean body weight gain of 18 g and 29 g after 7 and 14 days, respectively)
Gross pathology:
No gross pathologic findings were observed.
Interpretation of results:
study cannot be used for classification
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
/ Basic data given.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 2017
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation:
2 - 3 kg
- Housing:
Rabbits were immobilized during 24 h contact period
Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Type of wrap if used: The test material was retained under impervious sheeting on the clipped, intact skin of the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess fluid was removed to diminish ingestion.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: not reported
- For solids, paste formed: yes, test substance was moistened with corn oil
Duration of exposure:
24 h
Doses:
4 and 8 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations of the skin were performed at 1 h, on Day 7 and 14, animals were weighed on Day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 8 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period.
Clinical signs:
The high dose administration (8 g/kg bw) resulted in erythema (Day 1) in all 10 animals (female/males), edema (Day 7) in 2 males and 2 females. Desquamation was apparent on the dosed skin from Day 7 till Day 14 in 2 males and in all 5 females. Administration of the lower dose (4 g/kg bw) produced erythema (Day 1) and desquamation (Day 7 - 14) in all 10 animals (females/males).
Body weight:
The high dose administration (8 g/kg bw) resulted in emaciation (Day 7) in 2 males and 1 female, who recovered at Day 14, while in 1 female it was observed at Day 14. Administration of the lower dose (4 g/kg bw) had no impact on the body weight of any animal during the study period.
Gross pathology:
Gross pathologic examination revealed slightly mottled and dark red lungs in 2 males and enlarged kidneys and spleens in 2 females after administration of the high dose (8 g/kg bw), while administration of the lower dose (4 g/kg bw) produced no gross pathologic findings.

Table 1: Body weight changes

 

Dose
[mg/ kg bw]

Body weight change

Day 7
(range (mean) [g] )

Day 14
(range (mean) [g] )

Male

8000

-597 to -289 (-381)

-430 to -182 (-294)

4000

-566 to -130 (-352)

-344 to -57 (-191)

Female

8000

-606 to -2819 (-370)

-632 to -57 (-317)

4000

-466 to -247 (-348)

-264 to -32 (-158)

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
/ Basic data given.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 2015
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: The test substance was moistened with corn oil.
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:
4 h
Observation period:
7 days
Number of animals:
3 males/ 3 females
Details on study design:
TEST SITE
- Area of exposure: 2.45 x 2.45 cm² on dorsal skin
- Type of wrap if used: The dose is applied to the clipped, intact skin under a gauze patch and is loosely covered with impervious sheeting.

REMOVAL OF TEST SUBSTANCE
- Washing: Excess test substance was removed after contact.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48, 72 h and 7 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritant / corrosive response data:
No skin reaction was observed at any of the test sites of the 6 animals throughout the observation period.
Other effects:
Mortality/Clinical signs:
No mortality or clinical signs of toxicity were observed until the end of the observation period.
Sample residue was observed on 1/6 rabbits at 5 h.
Interpretation of results:
other: CLP/ EU GHS criteria not met, classification not required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 2017
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g (approx. 0.1 mL)
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 4, 24, 48, 72 h and Day 7
Number of animals or in vitro replicates:
3 males/ 3 females
Details on study design:
SCORING SYSTEM:
Cornea:
(A) Opacity - degree of density (most dense area taken for reading)
No opacity: 0
Scattered or diffuse area, iris details clearly visible: 1
Easily discernible translucent areas, iris details slightly obscured: 2
Opalescent areas, iris details not visible. pupil size barely discernible: 3
Opaque, iris invisible: 4

(A) Area of cornea involved
One-quarter or less, but not zero: 1
Greater than one-quarter, but less than half: 2
Greater than half, but less than three-quarter: 3
Greater than three-quarter, up to whole area: 4

Iris:
(A)
Normal: 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all), iris still reacting to light: 1
No reaction to light. hemorrhage, gross destruction: 2

Conjunctivae:
(A)
Vessels normal: 0
Vessels definitely injected above normal: 1
Diffuse, deep crimson red, individual vessels not readily discernible: 2
Diffuse beefy red: 3

(B)
No chemosis: 0
Any swelling above normal (includes nicitating membrane): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids about half closed to completely closed: 4
(C)
No discharge: 0
Any amount of discharge different from normal: 1
Discharge with moistening of the lid, and hairs adjacent to lids: 2
Discharge with considerable moistening around the eyes: 3

TOOL USED TO ASSESS SCORE: Fluorescein sodium solution (2%) was used to determine corneal injury before dosing and at readings after one day.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0.06
Max. score:
3
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 1 female showed conjunctivae (redness) scored 1 at 24 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 6 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
1 h after the application the test substance produced iritis (scored 1) in 1/6 animals persisting until the 24 h reading timepoint and slight conjunctival irritation in 4/6 animals (redness and chemosis, scored 1). The redness was then observed in all 6 animals at the 4 h reading time point but was reversible in 5/6 animals within 24 h, while for 1/6 animals (female) this was reversible at 48 h.
Discharge was observed 1 h after application of the test substance in all 6 animals. This reaction was reversible in 1 and 5 animals at 4 h and 24 h, respectively.
No corneal effects were apparent in any animal and time point.

Any other information on results incl. tables

Table 1: Individual scores of eye irritation

Rabbit #

Time [h]

Conjunctivae

Iris

Cornea

Redness

Chemosis (swelling)

1 (m)

1

1

1

0

0

4

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0

0

0

0

2 (m)

1

1

1

0

0

4

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0

0

0

0

3 (m)

1

0

0

0

0

4

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0

0

0

0

4 (f)

1

0

0

0

0

4

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0

0

0

0

5 (f)

1

1

1

1

0

4

1

1

1

0

24

1

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0.33

0

0

0

6 (f)

1

1

1

0

0

4

1

0

0

0

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

mean

0

0

0

0

Only the values from the reading time points 24, 48 and 72 h were used to calculate the mean values.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/ EU GHS criteria not met, classification not required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified