Reaction mass of Dimethyl [3-[(hydroxymethyl) amino]-3-oxopropyl] phosphonate and Dimethyl (3-amino-3-oxopropyl)phosphonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

EC Number:

243-528-9

EC Name:

Dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

Cas Number:

20120-33-6

Molecular formula:

C6H14NO5P

IUPAC Name:

dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

Constituent 2

Reference substance name:

Dimethyl (3-amino-3-oxopropyl)phosphonate

EC Number:

219-765-9

EC Name:

Dimethyl (3-amino-3-oxopropyl)phosphonate

Cas Number:

2526-69-4

Molecular formula:

C5H12NO4P

IUPAC Name:

dimethyl (3-amino-3-oxopropyl)phosphonate

Test material form:

liquid: viscous

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test system: Rabbit, Chbblbm: NZW (SPF)
Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf
Age at start of treatment: male: 15 weeks, females: 16 weeks
Body weight at start of treatment: male: 3.0 kg, females: 3.1 - 3.3 kg
Identification: By unique cage number and corresponding ear tags.
Acclimatization: four days under laboratory conditions after veterinary examination.

Conditions
Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour and hourly monitored environment with a temperature of 20 ± 3 °C, a relative humidity between 40-70 % (values above 70 % during cleaning process possible), 12 hours artificial fluorescent light (approx. 100 Lux)/12 hours dark, music during the light period.

Accommodation
Individually in stainless steel cages (size: 35.5 x 55.5 x 45 cm) equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, D-7830 Emmendingen).

Diet
Pelleted standard Kliba 341, Batch 66/91 rabbit maintenance diet ("Kliba", Kiingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum. Results of analysis for contaminants are included in this report.

Water
Community tap water from Itingen, ad libitum. Results of bacteriological, chemical and contaminant analyses are included in this report.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test article was applied undiluted as delivered by the sponsor.

Duration of treatment / exposure:

On test day 1, 0.1 ml of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control.

Observation period (in vivo):

The eyes of each animal were examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration. The irritation was assessed according to the Draize numerical scoring system. The corrosive properties of the test article and the staining of the treated eye were described and recorded.

Number of animals or in vitro replicates:

2 females and 1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: draize scoring

OBSERVATIONS
Viability/Mortality and Clinical Signs: Daily.
Body Weights: At the start of acclimatization, at day 1 of test (application day) and at termination of observation.
Irritation Scores:
The eyes of each animal were examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration. The irritation was assessed according to the following numerical scoring system. The corrosive properties of the test article and the staining of the treated eye were described and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7d

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7d

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7d

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

Results 10

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item DMPPA_701-402-5 is considered as non-irritant to the eye.

Executive summary:

The primary irritation potential of the test material was investigated by instillation of DMPPA_701-402-5 into one eye of each three young adult New Zealand rabbits. The treated eyes were not rinsed after substance application. Scoring of irritation effects were performed 1, 24, 48, 72 hours and 7 days after installation. No staining of the cornea and conjunctivae of the treated eyes by pigment or coloring of the test article was observed. Generally slight diffuse corneal opacity was observed in all three animals between 1 hour, 24 hours and 72 hours of observation respectively, however the scores were below threshold required for classification as per CLP criteria. Hence, the test article has to be classified as not irritant to the eye of rabbits.