Phosphonic acid, mixed C12-20-alkyl and C14-18-unsatd. alkyl derivs.

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 02 November 2011 and 16 November 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission Regulation (EC) No. 440/2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of Health of Government of the U.K., inspection 19-21 July 2011

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phosphonic acid, mixed C12-20-alkyl and C14-18-unsatd. alkyl derivs.

EC Number:

300-326-6

EC Name:

Phosphonic acid, mixed C12-20-alkyl and C14-18-unsatd. alkyl derivs.

Cas Number:

93925-25-8

Molecular formula:

Complex

IUPAC Name:

Phosphonic acid, mixed C12-20-alkyl and C14-18-unsatd. alkyl derivs.

Test material form:

liquid: viscous

Details on test material:

- Substance type: Organic
- Physical state: White liquid
- Analytical purity: Considered to be 100 % due to the UVCB character
- Lot/batch No.: 0100823714
- Expiration date of the lot/batch: 28 September 2012
- Storage condition of test material: Room temperature, in the dark
- Other: Date received at the test laboratory: 28 September 2011

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories U.K. Ltd., Oxon, U.K. The females were nulliparous and non pregnant.
- Age at study initiation: Eight to twelve weeks
- Weight at study initiation: At the start of the study the animals weighed at least 200 g (males 224 to 240 g, females 201 to 214 g). The weight variation did not exceed ± 20 % of the mean weight for each sixth weight variation did not exceed ± 20 % of the mean weight for each sex.
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with wood flakes. During the 24 h exposure period the animals were housed individually and in groups of five, by sex, for the remainder of the study.
- Diet: Ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, U.K.) throughout the study
- Water: Ad libitum throughout the study
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 % relative humidity
- Air changes: 15/h (at least)
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: On the day before treatment the back and flanks of each animal were clipped free of hair. The test item was applied as evenly as possible to an area of shorn skin using a graduated syringe.
- % coverage: 10 % of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 h exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing: After the 24 h contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.
- Time after start of exposure: The animals were returned to group housing for the remainder of the study period.

TEST MATERIAL
- Amount applied: 2 g of the test item were applied (given the relative density of 0.91 this corresponds to ca. 2.2 mL)
- Concentration: Pure test item was applied and no vehicle was used.
- Constant volume or concentration used: Yes (only one treatment)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw (sole dose)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: The test animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 h after dosing and subsequently once daily for the remaining observation period. Individual bodyweights were recorded prior to application of the test item on day 0 and on days 7 and 14.
- Necropsy of survivors performed: Yes. At the end of the study all animals were killed by cervical dislocation and were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Other examinations performed: After removal of the dressings and subsequently once daily for the remaining observation period, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize (1977). Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

- Draize JH (1977). Dermal and Eye Toxicity Tests. In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington, DC, U.S.A. 31 p

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All test animals survived and showed no clinical signs.

Mortality:

No mortality occurred.

Clinical signs:

other: None of the test animals showed signs of dermal irritation. Neither erythema nor edema, eschar formation or any other abnormalities were observed.

Gross pathology:

A cavity in each kidney, which was considered to be a genetic defect and not test item related, was noted at necropsy of one female. No abnormalities were noted at necropsy of the remaining animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Not acute toxic, LD0 is ≥ 2000 mg/kg bw and the LD50 is > than this sole dose, no difference to control

Executive summary:

The acute toxicity of the test item by dermal route was investigated in a GLP-compliant study using male and female Wistar rats according to the EU B.3 (2008) and OECD TG 402 (1987) protocols. The experiment is deemed valid, conclusive and thus suitable for assessment without restrictions.

A group of ten animals (five males and five females) was given a single, 24 h, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No mortality occurred and there were no signs of systemic toxicity or dermal irritation. All animals showed expected gains in bodyweight over the study period. During necropsy a cavity in each kidney, which was considered to be a genetic defect and not test item related, was noted at necropsy of one female test animal. No abnormalities were noted at necropsy of the remaining animals.

As the test item did not produce any effects the LD0 is ≥ 2000 mg/kg bw and the LD50 is > than this sole dose. It should be considered not acute dermally toxic and no indication for classification is given up to the upper relevance level of EU CLP Regulation (EC) No 1272/2008.