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:
1961
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable data which meets basic scientific principles, with acceptable restrictions (purity of the test substance not specified)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Hannover rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
Mean body weight of males at test initiation: ca. 160 g
Mean body weight of females at test initiation: ca. 144 g
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5000, 6400, 8000, 10000 mg/kg bw
No. of animals per sex per dose:
5 animals per treatment (mixed sexes)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 8 000 mg/kg bw
Mortality:
Mortality was 100 % at the highest tested dose of 10000 mg/kg bw, and 40 % at 8000 mg/kg bw (2 females). All animals of the 6400 and 5000 mg/kg bw groups survived. Mortalities occurred within the first 24 hours following treatment.
Clinical signs:
A series of symptoms indicative of toxicity were reported for all groups; these symptoms mainly included staggering, convulsive twitches, prone or lateral position and intermittent breathing. The surviving animals of the 8000 mg/kg bw group recovered within 5 days. In the 6400 and 5000 mg/kg bw groups, no more symptoms were seen after 2 days.
Gross pathology:
Necropsy of the animals that died during the observation period revealed fatty liver and moldered gastro-intestinal tracts. The survivors that were sacrificed at the end of the observation period of 7 days were inconspicuous.

CONCLUSION
The acute oral ALD50 (approximate lethal dose) of this TS was ca. 8000 mg/kg body weight.

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value was estimated on the basis of the observed mortalities and amounts to ca. 8000 mg/kg body weight.
Executive summary:

The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. Each test group consisting of 5 animals, i.e. 2 male and 3 female rats. Each animal received a single administration of an aqueous solution of test substance by gavage. Two concentrations of test substance in vehicle, 20 and 30 %, were used. the 20 % solution was used for the scheduled test dosages of 5000 and 6400 mg/kg bw, whereas the 30 % solution was used for the 8000 and 10000 mg/kg bw dosages. The application volume depended on the body weight of each test animal and ranged from 3.1 to 5.9 mL/animal.
The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observation period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities and amounts to ca. 8000 mg/kg body weight.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
BASF-Test: Test was performed in principle as described in OECD Guideline 403.
The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (room temperature). 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days.
GLP compliance:
no
Test type:
other: BASF Inhalation Test
Species:
rat
Strain:
other: Hannover
Sex:
male/female
Details on test animals or test system and environmental conditions:
Mean body weight at test initiation: ca. 152 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
saturated vapour
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
other: IRT (Inhalation Risk Test)
Exp. duration:
8 h
Remarks on result:
other: mortality 0/6 animals
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.061 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
8 h
Mortality:
All animals survived.
Clinical signs:
other:
Body weight:
The mean body weight was ca. 152 g at test initiation, and ca. 166 g at the end of the observation period.
Gross pathology:
No treatment related changes observed.

The inhalation of a enriched/saturated vapor-air-mixture caused no mortality within 8 h.

Interpretation of results:
other: LC50 value could be established because no mortalities were occured during the test. LC0 is 0.061 mg/L (saturated atmosphere)
Conclusions:
nontoxic if inhaled
Executive summary:

The sudy was performed according a standard inhalation hazard BASF Test. The principles of the performing of this test is similar with the requirements of the OECD guideline 403.

A saturated test atmosphere of test material was generated. 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days.

At this conditions 0/6 rats died after 8 h exposure (BASF AG 1961). Intermittent agitation directly after treatment ignition was the only clinical sign observed; there were no necropsy findings in the survivors after 7 d observation period. No LC50 value could be established because no mortalities were occured during the test. LC0 is 0.061 mg/L (saturated atmosphere).

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable data which meets basic scientific principles, with acceptable restrictions (purity of the test substance not specified)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
BASF-Test
GLP compliance:
no
Species:
mouse
Strain:
other: Tuebinger
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain: Tuebinger
Breeder: BASF AG
Mean body weight for the males: ca. 30 g
Mean body weight of the females: ca. 25 g
Route of administration:
intraperitoneal
Vehicle:
water
Doses:
3200, 3600 and 4000 mg/kg bw
No. of animals per sex per dose:
5
Details on study design:
TEST PROCEDURE
The study was conducted according to an internal BASF method. Several groups of 5-10 mice per sex and dose were treated intraperitoneally with preparations of the test substance as 20 % aqueous solution (w/v). Each of the low and the high test dose group (i.e. 3200 and 4000 mg/kg bw) consisted of 5 animals, i.e. 2 males and 3 females); the mid dose group consisted of a total of 10 animals (5/sex). Each animal received a single intraperitoneal injection of test solution and the application volume ranged between 16 and 20 mL/kg bw. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observation period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 800 mg/kg bw
Mortality:
Mortality was 100 % at the highest tested dose of 4000 mg/kg bw, and 10 % at 3600 mg/kg bw (1 female died); the animals died within the first 24 hours following treatment. No mortality was seen in the 3200 mg/kg bw group.
Clinical signs:
A series of symtoms indicative of toxicity were reported for all groups. These symptoms mainly included accelerated breathing, convulsion or convulsive twitches, tonic-clonic spasms, prone position and apathy; they almost were observed within the first 30 minutes following injection. The surviving animals of the 3600 and 3200 mg/kg bw group recovered within one day.
Gross pathology:
Necropsy of the animals that died during the observation period revealed pale liver and kidney (fatty ?). No further abnormalities were seen. The survivors that were sacrificed at the end of the observation period of 7 days were inconspicuous.
Executive summary:

The study was conducted according to an internal BASF method. Several  groups of 5-10 mice per sex and dose were treated intraperitoneally with preparations of the test substance as 20 % aqueous solution (w/v). Each of the low and the high test dose group (i.e. 3200 and 4000 mg/kg bw) consisted of 5 animals, i.e. 2 males and 3 females); the mid dose group consisted of a total of 10 animals (5/sex). Each animal received a  single intraperitoneal injection of test solution and the application volume ranged between 16 and 20 mL/kg bw. The animals were observed for mortality and for clinical symptoms of  toxicity. At the end of the observation period of 7 days, the surviving  animals were sacrificed for the purpose of necropsy; animals that died  during the observation period also were subjected to necropsy. The LD50 value was estimated on the basis of the observed mortalities. Mortality was 100 % at the highest tested dose of 4000 mg/kg bw, and 10 %  at 3600 mg/kg bw (1 female died); the animals died within the first 24 hours following treatment. No mortality was seen in the 3200 mg/kg bw group. A series of symtoms indicative of toxicity were reported for all groups. These symptoms mainly included accelerated breathing, convulsion or convulsive twitches, tonic-clonic spasms, prone position and apathy; they almost were observed within the first 30 minutes following injection. The  surviving animals of the 3600 and 3200 mg/kg bw group recovered within one day. Necropsy of the animals that died during the observation period revealed pale liver and kidney (fatty ?). No further abnormalities were seen. The survivors that were sacrificed at the end of the observation period of 7 days were inconspicuous. The lD50 value derived amounts to 3800 mg/kg bw/day.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable data which meets basic scientific principles, with acceptable restrictions (purity of the test substance not specified)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Principles of method if other than guideline:
BASF-Test
Two animals were treated for 20 hours with the test substance, which was applied onto the intact skin on the left side of the back; the application site covered a skin area of 2.5 cm x 2.5 cm. In addition, ear skin also was tested. The application volume was 2 mL of hygroscopic, partly diluted test material. The application site of the back was examined for skin reaction after 24, 48 and 72 hours, and after 6 and 8 days following treatment.
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals or test system and environmental conditions:
Body weight at test initiation: 2.3 and 2.93 kg, respectively.
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
2 mL
Duration of treatment / exposure:
20 hour(s)
Observation period:
8 d
Number of animals:
2
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 d
Remarks on result:
other: scaling observed at the test end, d8
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: scaling observed on d3 and at the test end, d8
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Interpretation of results:
study cannot be used for classification
Remarks:
Since the exposure to the test substance was performed for 20 h under occlusive conditions, the results has to be considered as overpredictive in comparison to results of actually recommended guideline studies (4 h exposition, semiocclusive conditions)
Executive summary:

The study was conducted according to an internal BASF method. Two animals were treated for 20 hours with the test substance, which was applied onto the intact skin on the left side of the back; the application site covered a skin area of 2.5 cm x 2.5 cm. In addition, ear skin also was tested. The application volume was 2 mL of hygroscopic, partly diluted test material. The application site of the back was examined for skin reaction after 24, 48 and 72 hours, and after 6 and 8 days following treatment.

No edema was observed. However, erythema was observed in animal1 and animal 2. Animal 1 showed a grading of 1.3 and animal 2 presented with a grading of 0.7. The erythema was reversible within 8 days and 72 hours, respectively. Since the exposure to the test substance was performed for 20 h under occlusive conditions, the results has to be considered as overpredictive in comparison to results of actually recommended guideline studies (4 h exposition, semiocclusive conditions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1961
Report date:
1961

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: BASF Test comparable to OECD Guideline 405
Principles of method if other than guideline:
BASF-Test. 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours as specified in OECD Guideline 405.
GLP compliance:
no
Remarks:
The study was performed prior to the adoption of the GLP requirements

Test material

Constituent 1
Chemical structure
Reference substance name:
2-pyrrolidone
EC Number:
210-483-1
EC Name:
2-pyrrolidone
Cas Number:
616-45-5
Molecular formula:
C4H7NO
IUPAC Name:
pyrrolidin-2-one
Details on test material:
Name of test material (as cited in study report): Pyrrolidone, distilled roh
Physical state: solid
Degree of Purity: no data

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
Body weight at test initiation: 2.46 and 3.2 kg, respectively

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: physiological saline was applied to the left eye, which served for control
Amount / concentration applied:
Amount applied: 0.05 mL
Duration of treatment / exposure:
unspecified (eyes were not washed)
Observation period (in vivo):
until complete reversibility of the effects was observed: 6 d (animal 1)/7 d (animal 2)
Number of animals or in vitro replicates:
2
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed

SCORING SYSTEM: Draize (The original findings for both animals (referred to as 1 and 2) were converted into a numerical scoring system according to Draize)

TOOL USED TO ASSESS SCORE: fluorescein (at the final reading)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: based on effects in two animals
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
other: based on effects in two animals
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24-72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: based on effects in two animals
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
swelling
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
other: based on effects in two animals
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects

Any other information on results incl. tables

Reading animal  cornea      iris  conjunctivae
         No.   opacity           redness  swelling
24 h    1 2 0 1 0
24 h    2 2 0 2 0
48 h    1 2 0 1 0
48 h    2 2 0 1 0
72 h    1 2 0 0 0
72 h    2 2 0 0 0
6 d     1 0 0 0 0
6 d     2 2 0 0 0
7 d     2 0 0 0 0
relevant for classification:          
mean    1 2 0 0.7 0
24-72h  2 2 0 1 0
         mean  2 0 0.8 0

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
2-pyrrolidone is considered to be irritating to the rabbit eyes (Category II).
Executive summary:

In a study in rabbits 2-pyrrolidone was investigated for its potential to induce eye irritation/corrosion. 50 µL of the test substance were applied to the conjunctival sac of one eye in 2 animals. The animals were observed after 10 min, 1 and 3 h on the day of treatment and up to 8 days afterwards. Findings were recorded daily. The eyes were not washed out after 24 hours as specified in OECD Guideline 405. The test item produced in the present eye irritation test alterations at the cornea and conjunctivae. The iris was not affected. The observable effects were fully reversible until the end of the study.

Based on corneal opacity (24-72h score is 2 across 2 test animals), 2-pyrrolidone is classified for its eye irritation potential as follows: irritating to eyes Cat.2 (EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulations No. 1271/2008).