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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
publication
Title:
The Mucosal Toxicity of Different Benzalkonium Chloride Analogues Evaluated with an Alternative Test Using Slugs
Author:
Els Adriaens, Kristof Dierckens,
Tiene G. M. Bauters, Hans J. Nelis,
Freddy van Goethem, Phillipe Vanparys, and Jean Paul Remon
Year:
2001
Bibliographic source:
Pharmaceutical Research, Vol. 18, No. 7, 2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Principles of method if other than guideline:
Methodology followed is the one described in publication : P. Vanparys, G. Deknudt, M. Sysmans, G. Teuns, W. Coussement, and H. Vancauteren. Evaluation of the bovine corneal opacity permeability assay as an in vitro alternative to the Draize eye irritation test. Toxicol. Vitro 7:471–476 (1993)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Specific details on test material used for the study:
3 test materials : Benzalkonium chloride (BAC-mix) (60–70% C12, 30–40% C14, and < 5% C16), benzyldimethylhexadecylammoniumchloride (BAC-C16), benzyldimethyltetradecylammoniumchloride (BAC-C14), and benzyldimethyldodecylammoniumbromide (BAC-C12)

Test animals / tissue source

Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Bovine eyes were excised in the slaughterhouse and used within 3 hours after killing. The eyes were immersed in Hanks’ balanced salt solution. Three corneas were used per treatment. The corneas were dissected with a 2–3 mm rim of sclera and mounted in the cornea holders with the endothelial side downward. The anterior and posterior compartment of the cornea holder were filled with Minimal Essential Medium (MEM). After an incubation period of 1 h in a water bath at 32°C the MEM solution was removed from both compartments and replaced with fresh medium.

Test system

Vehicle:
physiological saline
Controls:
yes, concurrent vehicle
yes, concurrent positive control
Amount / concentration applied:
20%
Duration of post- treatment incubation (in vitro):
After an incubation period of 10 min the test medium was removed and the epithelium was washed with Minimal Essential Medium Medium solution
Number of animals or in vitro replicates:
3 for each test material

Results and discussion

In vitro

Resultsopen allclose all
Irritation parameter:
in vitro irritation score
Run / experiment:
BAC-C16 20% (g/g)
Value:
ca. 89.4
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Remarks:
IVS +/- 20.3
Irritation parameter:
in vitro irritation score
Run / experiment:
BAC-C14 20% (g/g)
Value:
ca. 124.6
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Remarks:
IVS +/- 3.4
Irritation parameter:
in vitro irritation score
Run / experiment:
BAC-C12 20% (g/g)
Value:
ca. 198.1
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Remarks:
IVS +/- 13.1
Irritation parameter:
in vitro irritation score
Run / experiment:
BAC-mix 20% (g/g)
Value:
ca. 150.8
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Remarks:
IVS +/- 21.0

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
These results confirmed severe eye irritant potential with the in vitro BCOP assay in which the following rank order of increasing corneal injury was obtained: BAC-C16
Executive summary:

In an in vitro study which protocol is similar with OECD 437 (BCOP), various alkyl chain length benzalkonium chlorides were showed to be very severe eye irritant at 20%.