Tetrabutylphosphonium bromide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 June 2006 - 03 July 2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study conducted according to GLP principles, methods used equivalent to OECD guideline 404, but with deviations (0.081mg instilled instead of 0.1mg). As this amount resulted in severe effects, the test is regarded to be sufficient to fill this endpoint.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Lower amount test substance instilled, instillation into both eyes (one washed, one unwashed)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrabutylphosphonium bromide

EC Number:

221-487-8

EC Name:

Tetrabutylphosphonium bromide

Cas Number:

3115-68-2

Molecular formula:

C16H36P.Br

IUPAC Name:

tetrabutylphosphanium bromide

Test material form:

other: waxy solid

Details on test material:

- Name of test material (as cited in study report): CYPHOS 442 (CT-851-06)
- Substance type: organic
- Physical state: White waxy solid (odorless)
- Storage condition of test material: Room temperature and humidity

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA, USA
- Age at study initiation: 3-4 months
- Weight at study initiation: 3.4 kg
- Housing: individually in suspended cage
- Diet: PMI Rabbit Chow, provided daily
- Water: ad libitum
- Acclimation period: at least 3 days

ENVIRONMENTAL CONDITIONS
- Experiments conducted in temperature-controlled animal room
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 June 2006 - 03 July 2006

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.081mg

Duration of treatment / exposure:

Single instillation

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was instilled in both eyes, one eye remained unwashed, one eye was flushed by lukewarm water for one minute.
- Time after start of exposure: 20 to 30 seconds

SCORING SYSTEM: Following numerical Draize technique (Draize, J.H. et al., J. Pharm. Exp. Ther. 82: 377-390, 1944), additional signs were described.

TOOL USED TO ASSESS SCORE: Mini-Maglite flashlight

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

Corneal opacity, iritis and conjunctival irritation persisted until termination of the experiment (day 7). Pannus was noted on day 7. Discharge was noted at every observation time point.

Other effects:

Vocalization was noted post-dose.

Any other information on results incl. tables

In the washed eye, corneal opacity and iritis were noted that had cleared on day 7. Conjunctival irritation was still noticeable at day 7. Animal exhibited lethargy, prostration and laboured breathing at time of ocular dosing and instances of lethargy and few faeces post-dosing.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

An eye irritation study was performed by instillation of 0.081mg tetrabutylphosphonium bromide in each eye of a rabbit. One eye remained unwahsed, one eye was flushed with lukewarm water. This resulted in severe effects during 7 days, after which the animal was sacrificed. Based on these results, the test substance is classified corrosive to the eye (cat. 1).

Executive summary:

An eye irritation study was performed by instillation of 0.081mg tetrabutylphosphonium bromide in each eye of a rabbit. The test was done following GLP principles. One eye remained unwashed, one eye was flushed with lukewarm water. This resulted in severe irreversible effects during 7 days in the unwashed eye, after which the animal was sacrificed. Based on these results, the test substance is classified corrosive to the eye (cat. 1).