Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results.

Data source

Reference
Reference Type:
other: TSCA 8e submission
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Study was designed to follow the Draise eye irritation test method.

Reference:
Draize, John H., Woodard, Geoffrey, and Calvery, Herbert 0., Methods for the Study of Irritation and Toxcity of Substances Applied Topically to
the Skin and Mucous Membranes. J. Pharm. & Exp. Ther. 82, 377 (1944).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Benzyltrimethyl Ammonium Chloride (60% solution in water). Lot No. 59

Test animals / tissue source

Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
male and female rabbits weighing 2.3 - 3.0 were used.

Test system

Controls:
not specified
Amount / concentration applied:
0.1 ml initially, followed by 0.05 or 0.03 ml. See Table 1.
Duration of treatment / exposure:
Report does not mention whether eyes were washed.
Observation period (in vivo):
Animals were observed for at least 24 hours
Number of animals or in vitro replicates:
One male was tested at 0.1 ml. Other rabbits were tested at lower doses.
Details on study design:
Exactly 0.1 ml of undiJuted test material was instilled into the conjunctival sac of the right eye of one rabbit. Before a second rabbit could be similarly
exposed, the first rabbit convulsed and died. The dose was reduced to 0.05 ml and administered to the second rabbit. This rabbit died 160 seconds later. The dose was reduced to 0.03 ml and administered to each of 5 rabbits. All of the animals exhibited severe pharmacotoxic symptoms. Three of the animals died 2-3 minutes after dose administration. Tne other 2 rabbits survived and recovered within 24 hours. The cornea, iris and palpebral ccnjunctiva were examined frequently for irritation and injury for a period of approximately 1/2 hour .

In evaluating the average irritation present, the mean scores for erythema and edem.a of the intact test sites after 24 and 72 hours were added. Similarly, the mean scores for erythema and edema of the abraded test sites after 24 and 72 hours were added. These two values were totaled and divided by four to obtain the mean primary irritation score.

Results and discussion

In vivo

Irritant / corrosive response data:
Transient conjunctival irritation (discharge) was noted shortly after instillation of the test material. The discharge subsided within 10-15 minutes. No corneal lesions were noted.
Other effects:
The followiing pharmacotoxic symptoms were noted within 30-60 seconds after instillation of Benzyltrimethyl Ammonium Chloride: chewing, lacrimation. miosis, muscular weakn.ess. incontinence, cyanosis. ataxia, skeletal muscle fibrillations and convulsions. The two animals that survived recovered from most symptoms within 5-10 minutes. Miosis was observed up to 24 hours.

Any other information on results incl. tables

See Acute Toxicity: other routes for a table on Time to Death.

Applicant's summary and conclusion

Conclusions:
Transient conjunctival irritation (discharge) was noted shortly after instillation of the test material. The discharge subsided within 10-15 minutes. No corneal lesions were noted.
Executive summary:

The eye irritation potential of the test material was examined. Transient conjunctival irritation (discharge) was noted shortly after instillation of the test material. The discharge subsided within 10-15 minutes. No corneal lesions were noted. However, 3 of 6 rabbits dosed with 0.03 ml died within 3 minutes following instillation of test material onto the eye.