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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31.12.1991 till 27.01.1992

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Swiss Principles of Good Laboratory Practice (Good Laboratory Practice (GLP) in Switzerland, Procedures and Principles, March 1986)

Test type:

standard acute method

Limit test:

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: EN 746916/1991
- Expiration date of the lot/batch: September, 1996

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, protected from light at room temperature (approx. 20 °C)
- Stability under test conditions: stable ; expiration date: September, 1996

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4
CH-4414 Füllinsdorf
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: males: 10 weeks; females: 12 weeks
- Weight at study initiation: males: 237 - 248 g; females: 205 - 216 g
- Housing: Individually in Makrolon type-2 cages ( size: 16.5 x 22 x 14 cm) with standard softwood bedding
- Diet: ad libitum; Pelleted standard K l i b a 343, Batch 87/91 rat maintenance diet (" Kliba",Klingentalmuehle AG, CH-4303 Kaiseraugst)
- Water: ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 2 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) /12 hours dark

IN-LIFE DATES: From January 7 to 21, 1992

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface. The test article was applied undiluted. Only those animals with no injury or irritation on the skin were used in the test . On test day 1, the test article was applied evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Twenty-four hours after the application , the dressing was removed. The treated skin was washed with lukewarm tap water, dried with disposable paper towels and the skin reaction was assessed according to the method of Noakes and Sanderson.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Test days 1 ( pre-administration) , 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, mortality, body weight,organ weights, necropsy

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: The following local signs were observed: 2000 mg/kg: males/females - scales (back) ( 9 ) ; skin yellow (back) (10). The animals had recovered from local symptoms within 11 to 14 days of observation. No systemic symptoms were observed.

Gross pathology:

no macroscopical organ findings noted

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 (median lethal dose) of DMPPA_701-402-5 after single dermal administration to rats of both sexes, observed over a period of 14 days, is >2000 mg/kg body weight

Executive summary:

In an acute dermal toxicity study carried out according to OECD 402 guideline, the test article DMPPA_701-402-5 was applied to the skin of rats of both sexes for 24 hours at a single dose of 2000 mg/kg. No death was observed during the study. No adverse effects were seen except local signs such as scales (back) ( 9 ); skin yellow (back) (10). The animals were recovered from local symptoms within 11 to 14 days of observation. No systemic symptoms were observed.

Based on these observations, the LOGIT-Model could not be applied to the observed rate of death. Therefore, the LD₅₀ (median lethal dose) of DMPPA_701-402-5 after single dermal administration to rats of both sexes, observed over a period of 14 days, is >2000 mg/kg body weight. Based on the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, DMPPA_701-402-5

does not have to be classified for acute dermal toxicity.