Methyl hydrogen octadecylphosphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 30 2004 - April 6 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl hydrogen octadecylphosphonate

EC Number:

246-905-6

EC Name:

Methyl hydrogen octadecylphosphonate

Cas Number:

25371-55-5

Molecular formula:

C19H41O3P

IUPAC Name:

methoxy(octadecyl)phosphinic acid

impurity 1

Reference substance name:

Octadecylphosphonic acid

EC Number:

225-216-4

EC Name:

Octadecylphosphonic acid

Cas Number:

4724-47-4

Molecular formula:

C18H39O3P

IUPAC Name:

octadecylphosphonic acid

impurity 2

Reference substance name:

Dimethyl octadecylphosphonate

EC Number:

246-904-0

EC Name:

Dimethyl octadecylphosphonate

Cas Number:

25371-54-4

Molecular formula:

C20H43O3P

IUPAC Name:

dimethyl octadecylphosphonate

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals were housed individuallyin suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for the Care and Use of Laboratory Animals. PMI certified Rabbit Chow and municipal tap water treated by reverse osmosis was available ad libitum throughout the studyENVIRONMENTAL CONDITIONSTemperature - 20-22°CRelative Humidity - 44- 60%Light Cycle - 12-hour light / 12-hour dark cycleVentilation - 10-15 air changes/hour

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

15 seconds

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 male New Zealand White rabbits

Details on study design:

Three male rabbits were used to evalutae the potential irritant and/or corrosive effects of MMOP. Each of the three rabbits received 0.1 mLK of the neat test article in the conjunctival sac of the right eye. The contralateral ete of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.78

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.443

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.67

Reversibility:

fully reversible

Irritant / corrosive response data:

Exposure to the test article produced corneal opacity in 3/3/ test eyes by the 24-hour scoring interval. The corneal opacity resolved completley in 2/3 test eyes by the 72-hour scoring interval and the remaining eye by the end of day 7. Iritis was noted in 2/3 test eyes by the 24 hour scoring interval by the end of the 24 hour scoring interval and resolved compleley in 1/3 test eyes by 48 hours and in the remaining eye by day 7. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 tet eyes at the 1-hour scoring interval. The conjunctival irritation reslved completley in 3/3 test eyes by day 7. Additional ocular findings included slight dulling of the normal luster of the cornea (2/3 test eyes) and sloughing of the corneal epithelium (1/3 test eyes). All effects were fully reversible by day 7.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the study design MMOP is not considered to be an eye irritant under CLP

Executive summary:

The potential irritant and/or corrosive effects of MMOP were evaluated on the eyes of New Zealand White rabbits. Each of three rabbits received 0.1mL of the test article in the conjunctival sac of the right eye. the contralateral eye of each animal remained untreated and served as a control. Test and control eyes were examined for signs of irritation for up to 7 days following dosing.

Exposure to the test article resulted in corneal opacity in 3/3 test eyes by the 24 -hour scoring interval which was confirmed by positive fluorescein dye retention. The corneal opacity resolved completely in 2/3 test articles by the 72 -hour scoring interval and i the remaining test eye but study day 7. Iritis was observed in 2/3 test eyes by the 24 -hour scoring iterval and resolved fully in 1/3 test eyes by the 48 -hour scoring pont and in the remaining test eye by study day 7. Conjunctivitis (redness, swelling and discharge) was noted in 3/3 test eyes at the 1 -hour scoring interval, which had fully resolved in 3/3 test eyes by day 7. Additional ocular findings included slight dulling of the normal luster of teh cornea (2/3 test eyes) and sloughing of the corneal epithelium (1/3 test eyes). All effects were fully reversible by day 7.

Based on the EEC labelling criteria. MMOP is not considered to be an occular irritant.