Dialkyl C18 and C18-unsaturated phosphonates

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 July to 01 August 2017.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Due to technical reasons, temperature values (maximum of 25.7 °C) outside the expected range of 22 ± 3 °C were recorded during the study. However, this minor deviation was considered not to adversely affect the results of or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dialkyl C18 and C18-unsaturated phosphonates

EC Number:

701-298-1

Cas Number:

64051-29-2

Molecular formula:

Not applicable for a UVCB Substance

IUPAC Name:

Dialkyl C18 and C18-unsaturated phosphonates

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Alkenyl phosphonate
- Expiration date of the lot/batch: 09 September 2017
- Purity test date: 08/06/2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25 ºC, below 70 RH%)
- Stability under test conditions: yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld.
- Females (if applicable) nulliparous and non-pregnant: yes.
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 223 g and 271 g
- Fasting period before study: yes
- Housing: Individual caging
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1 – 25.7 °C
- Humidity (%): 31 – 67 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10% area of the total body surface.
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): YES
- Time after start of exposure: 24 hours.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14 just before necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

None.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

Alkenyl phosphonate did not cause mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study.

Gross pathology:

At necropsy, a few crusts were seen on the skin at the lumbar area in 3 male and 3 female animals. Besides this, there was no evidence of macroscopic observations at a dose level of 2000 mg/kg bw.

Other findings:

Very slight to well-defined erythema in 10/10 animals (Day 1-5 or 1-6), very slight to slight oedema in 9/10 animals (Day 1-6) and crust in 9/10 animals were seen at the treated area after treatment with the test item. Besides these, no other local dermal signs were observed during the 14 days observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute dermal median lethal dose (LD50 value) of the test item Alkenyl phosphonate was found to be above 2000 mg/kg bw in male and female rats. Therefore, Alkenyl phosponate is not classified according to EU criteria.

Executive summary:

The acute toxicity of Alkenyl phosphonate was investigated following administration of a single dermal dose to rats, in compliance with OECD Guideline No. 402. A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24-hour exposure followed by a 14 day observation period.

No mortality occurred following dosing and no clinical signs were observed. Very slight to well-defined erythema in 10/10 animals (Day 1-5 or 1-6), very slight to slight oedema in 9/10 animals (Day 1-6) and crust in 9/10 animals were seen at the treated area after treatment with the test item. Besides these, no other local dermal signs were observed during the 14 days observation period. Slight body weight loss was observed in three females following treatment, but the animals recovered the lost weight during the second week of the observation period. The body weight of the other treated animals during the study showed no indication of a test item-related effect. At necropsy, a few crusts were seen on the skin at the lumbar area in 3 male and 3 female animals. Besides this, there was no evidence of macroscopic observations at a dose level of 2000 mg/kg bw.

Under the conditions of this study, the acute dermal median lethal dose (LD₅₀value) of the test item Alkenyl phosphonate was found to be above 2000 mg/kg bw in male and female. Therefore, no classification is required according to EU criteria.