Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
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:
no guideline available
Principles of method if other than guideline:
Due to the results of an eye irritation study with 0.1 ml of test material deposited in the conjunctival sac, additional studies were conducted with smaller doses to define the time to death or survival for at least several minutes.

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
Limit test:
no

Test material

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

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Young albino rabbits of theNew Zealand strain weree used to evaluate the eye irritating properties of the test material.

Three males and four females were used for this study.

Administration / exposure

Route of administration:
other: test material was placed in the conjunctival sac
Vehicle:
unchanged (no vehicle)
Details on exposure:
Test material was deposited in the conjunctival sac and the rabbit was observed for at least 24 hours or death occurred.
Doses:
Various, see Table 1 below.
No. of animals per sex per dose:
Various, see Table 1 below.
Control animals:
not specified
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.
Statistics:
No data

Results and discussion

Mortality:
See Table 2 below
Clinical signs:
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.

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.
Body weight:
No data.
Gross pathology:
No data.
Other findings:
No additional information available.

Any other information on results incl. tables

Table 2 Mortality observed following instillation of test material into the eye of rabbits.

 Dose Level (ml)  Dose Level (mg/kg)  Sex  Time of Death
 0.1  41.3  M  135 seconds
 0.05  21.7  F  160 seconds
 0.03  11.0  F  170 seconds
 0.03  12.1  F  120 seconds
 0.03  12.1  M  animal recovered
 0.03  12.6  M  165 seconds
 0.03  10.1  F  animal recovered

Applicant's summary and conclusion

Conclusions:
This study demonstrated the high degree of toxicity of the test material when deposited in the eye of albino rabbits. Death occurred very rapidly in rabbits dosed with the test material. At the lowest dose examined, 0.03 ml, three of six rabbits died within 3 minutes.
Executive summary:

This study was designed to examine the eye irritation potential of the test material. This study also demonstrated the high degree of toxicity of the test material when deposited in the eye of albino rabbits. Death occurred very rapidly in rabbits dosed with the test material. At the lowest dose examined, 0.03 ml, three of six rabbits died within 3 minutes.