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

Endpoint summary

Description of key information

DMPPA_701-402-5 was found to be not irritating to the skin as well as eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from Oct 2003 till May 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive sealing of the application site

GLP compliance:

yes (incl. QA statement)

Remarks:

Nederland GLP

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 137244407
- Expiration date of the lot/batch: July, 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding facility JRF
- Weight at study initiation: 2.14 -2.18 kg
- Housing: Individually, stainless steel wire meshed cages
- Diet: Rabbit pellet diet from Amrut feeds by Pranav Agro; ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 63-64
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12 h

IN-LIFE DATES: From: 29 Jan 2004 To: 3 Feb 2004

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml of undiluted Aflammit KWB

Duration of treatment / exposure:

4h

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Dorso lumbar region at contralateral site
- % coverage: 6cm²
- Type of wrap if used: Meditape 330 hypo-allergic surgical tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cotton soaked in distilled water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h

SCORING SYSTEM:
- Method of calculation: Draize method

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Other effects:

No clinical signs related to treatment other than dermal reactions were observed during the experimental period.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is classified as not irritating to the skin of rabbits.

Executive summary:

Skin irritation study was carried out with Aflammit KWB according to OECD 404 guideline in NZW rabbit (Semi-occlusion). Under the conditions of this experiment, test substance was found to cause a primary irritation score of 0.00 when applied to healthy intact rabbit skin. No clinical signs related to treatment other than dermal reactions were observed during the experimental period. Based on the study results the test article is classified as not irritating to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

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.

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.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

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

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

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7d

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7d

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

One fully reliable in vivo study is available (Hoff, N. Skin irritation / corrosion (in vivo)) conducted according to OECD 404 and GLP using semi-occlusive application of 0.5 ml to the intact left flank of each of three young adult New Zealand White rabbits. The individual mean score for erythema/eschar and oedema for each of the three animals across 3 scoring times (24, 48 and 72 hours after patch removal) was 0.33. In the area of application, no staining of the treated skin by pigment or coloring of the test article was observed. Based on these results the substance is deemed not to be irritating.

 

- eye irritation/corrosion:

One fully reliable in vivo study is available (Hoff, N. Eye irritation) conducted according to OECD 405 and GLP using the conjunctival sac of rabbit eyes. The primary irritation potential of the test material was investigated by installation of DMPPA_701-402-5 into one eye of each three young adult 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. Under the conditions of this experiment, DMPPA_701-402-5 was found to cause a primary irritation score of: 3.00, when applied to the conjunctival sac of the rabbit eye. Due to these results described, the test article had to be classified as not irritant to the eye of rabbits.

 

Respiratory irritation:

no data available

Justification for classification or non-classification

- skin irritation/corrosion:

Based on the above stated assessment of the skin irritation potential of DMPPA_701-402-5 (individual mean score for erythema/eschar and oedema for each of the three animals across 3 scoring times = 0.33) the substance does not need to be classified according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- eye irritation/corrosion:

Based on the above stated assessment of the eye irritation potential of DMPPA_701-402-5, the substance does not need to be classified according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

- respiratory irritation:

As no data on respiratory irritation is available for DMPPA_701-402-5 a classification is not possible according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.