Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
454-210-6
EC Name:
-
Cas Number:
13106-24-6
Molecular formula:
C13 H30 N . C H3 O4 S
IUPAC Name:
tributyl(methyl)azanium methyl sulfate
Details on test material:
Substance Number: 97/272
Batch number: 601
Degree of purity: 101 g/100 g (H-NMR)
Physical state/appearance: Solid (congealed melt), white
Storage conditions: Room temperature.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals: New Zealand White (SPF)
Age: Young adult animals
Acclimatization period: At least one week.
Room temperature/relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees celsius for temperature and of 30-70 % relative humidity. There were no deviations from these ranges wgich influenced the results of the study.
Day/night rhythm: 12 h/12 h (6.00 A.M. - 6.00 P.M./6.00 P.M. - 6.00 A.M.)
Type of cage: Stainless steel wire mesh cages with grating, floor area 3000 cm2.
No. of animals per cage: Single housing.
Bedding: No bedding in the cages; sawdust in the waste trays.
Drinking water: About 250 ml tap water per animal per day.
Diet: Kliba-Labordiet, Klingentalmuehle AG, Kaiseraugst, Switzerland. About 130 g per animal per day.
Analysis of drinking water: The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory.
Analysis of feed: The feed used in the study was assayed for chemical and microbiological contaminants.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
15 d
Number of animals or in vitro replicates:
3
Details on study design:
Both eyes of the animals were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used in the study.
Acclimatization period: At least 1 week.
Weight determination: Shortly before application of the test substance.
Route of application: Single application to the conjunctival sac of the right eyelid. The substance was washed out with tap water about 24 hours after application (before 24 hour reading).
Application volume: 0.1 ml of the at about 80 degrees centigrade heated test substance. Before application it was cooled down to body temperature.
Observation period: 15 d.
Readings: 1 h, 24 h, 48 h, 72 h, 8 d, and 15 d after application.
Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays, and on public holidays.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 d
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0.2
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
1.2
Reversibility:
fully reversible within: 15 d
Irritant / corrosive response data:
No effects on the cornea were observed.
In one animal an effect on the iris after 24 h and 48 h after application was observed, which was fully reversible within 72 h.
Conjunctivae redness was markedly increased from 1 h to 8 d after application in all 3 animals. These effects were fully reversible within 15 d.
Chemosis was observed in all 3 animals after 1 h and 24 h.Between 48 h and 72 only 2 animals showed chemosis. After 15 d no chemosis was observed in any animal. Discharge was observed in all animals between 1 h and 72 h. After 8 day discharge was only seen in 1 animal which also suffered from suppuration. After 15 d discharge was fully reversible in all animals and also suppuration of one animal was reversible.
Details see table 1.

Any other information on results incl. tables

Table 1: Irritation/Corrosion scores after treatment of animals with test substance.

 Readings  Animal Cornea-opacity Cornea-area  Iris Conjunctiva-Red  Conjunctiva-swelling   Conjunctiva-discharge
 1 h  01  0  0  2  1  3
   02  0  0  2  2  3
   03  0  0  2  2  2
 24 h  01  0  0  3  2  2
   02  0  0  3  1  1
   03  0  1  3  2  3
 48 h  01  0  0  2  1  1
   02  0  0  3  0  1
   03 0  1  3  2  3
 72 h  01 0  0  2  1  1
   02  0  0  2  0  1
   03  0  0  2  2  1
 8 d  01  0  0  1  0  1
   02  0  0  1  0  0
   03  0  1  1  0
 15 d  01  0  0  0  0  0
   02  0  0  0  0  0
   03  0  0  0  0  0
               
 Mean 01   0.0  0.0  2.3  1.3  
  02  0.0  0.0  2.7  0.3  
  03  0.0    0.7  2.7  2.0  
 Mean    0.0    0.2  2.6  1.2  

Applicant's summary and conclusion