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

Endpoint summary

Description of key information

Not acute toxic, no differences to control

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 15 March 1974 and 18 April 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Valid and conclusive pre-GLP study comparable to guideline, basic data reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

yes

Remarks:

Necropsy omitted, administered volume in excess of guideline recommendations

GLP compliance:

no

Remarks:

The experiment was performed before the first GLP standard was defined by FDA in 1976, therefore no formal GLP was possible. Nonetheless it can be assumed that comparable standards applied as the test was conducted in a specialized laboratory.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sherman-Wistar (albino)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Animals weighed between 200 and 250 g.
- Fasting period before study: Test animals were fasted overnight (24 h) before dose administration.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2, 4, 8, 16, or 32 mL/kg; given the submission item relative density value 910 kg/m³, the doses correspond to 1820, 3640, 7280, 14,560 and 29,120 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Daily observation, weighing at study initiation only
- Necropsy of survivors performed: No
- Other examinations performed: The animals were observed for 14 d for signs of toxicity and mortality.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 32 mL/kg bw

Based on:

test mat.

Remarks on result:

other: Mortality: 1/5 and 2/5 at 16 and 32 mL/kg, respectively

Sex:

male

Dose descriptor:

LD50

Effect level:

> 29 120 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Converted using the density value 910 kg/m³

Sex:

male

Dose descriptor:

LD0

Effect level:

>= 7 280 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No difference to control

Mortality:

At 16 mL/kg bw one test animal was found dead on day 2.
At 32 mL/kg bw one test animal was found dead on day 1 and a second one on day 2.

Clinical signs:

other: No observations

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Not acute toxic, LD0 ≥ 8 mL/kg bw or ≥ 7280 mg/kg bw and LD 50 > 32 mL/kg bw or > 29,120 mg/kg bw

Executive summary:

The acute toxicity of the test item by oral route was investigated in a pre-GLP study using male albino Sherman-Wistar rats according to a protocol comparable to the OECD TG 401 (1987) standards. At variance to the guideline no necropsy was performed and the test item was applied in a volume exceeding 1 mL per 100 g bw. The experiment was performed before the first GLP standard was defined by FDA in 1976, therefore no formal GLP was possible. Nonetheless it can be assumed that comparable standards applied as the test was conducted in a specialized laboratory. The reporting is limited but sufficient information is given. The experiment is deemed valid, conclusive and thus suitable for assessment with minor restrictions.

Groups of test animals, each consisting of 5 individuals weighing between 200 and 250 g were fasted overnight and administered 2, 4, 8, 16 or 32 mL/kg by stomach tube, which corresponds to 1820, 3640, 7280, 14,560 and 29,120 mg/kg bw. The animals were observed for 14 d post exposure for signs of toxicity and mortality.

Mortality was observed at 16 and 32 mL/kg, where 1 and 2 animals died, respectively, until day 2. No observation of sublethal effects was made. Therefore the LD50 is > 32 mL/kg bw or > 29,120 mg/kg bw. At 8 mL/kg bw or 7280 mg/kg bw no mortality occurred, which means that the LD0 (discriminating dose) can be assigned to be greater or equal to this level.

In summary no effects were observed in the classifiable range up to 2000 mg/kg bw (CLP) or even 5000 mg/kg bw (GHS). Therefore, on the basis of this study, classification is not required for the test item in accordance with EU CLP Regulation (EC) No 1272/2008 and the absence of acute oral toxicity is evidenced.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The sole available study is considered a valid and conclusive pre-GLP study comparable to guideline. As the basic data are reported and the result indicates the absence of mortality far above the relevant levels of CLP or GHS, the experiment is deemed suitable for assessment with minor restrictions.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

reference to other study

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Commission Regulation (EC) No. 440/2008

Deviations:

no

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

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

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

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The sole available study is considered a valid and conclusive guideline study under GLP, which is suitable for assessment without restrictions.

Additional information

Oral route

The acute toxicity by oral route was investigated in a pre-GLP study (Gabriel 1974, Biosearch Report on Acute Oral Toxicity - Rats) using male albino Sherman-Wistar rats according to a protocol comparable to the OECD TG 401 (1987) standards. The experiment is deemed valid, conclusive and thus suitable for assessment with minor restrictions. No mortality and no signs of toxicity were recorded up to 7280 mg/kg bw. Therefore the submission item should be regarded as not acute toxic by oral route.

Inhalation route

No experimental data from a study on acute toxicity by inhalation are available. Testing has been waived in accordance with column 2 restrictions. In view of the low vapour pressure (0.00043 Pa at 25 °C, Tremain & Atwal 2011, Harlan Report no. 41103264) leading to low volatilization and the expected absence of airborne forms of the submission item in the supported uses, inhalation is deemed an irrelevant route. In absence of any toxic or local effects via the oral and dermal route, absence acute toxicity by inhalation up to relevant levels can be expected. Therefore the submission item is deemed not acute toxic by inhalation.

Dermal route

The acute toxicity by dermal route was investigated in a GLP-compliant study (Sanders 2012, Harlan Report no. 41103266) 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. No toxicity and no local effects such as erythema, edema, eschar formation or any other abnormalities were observed at the sole test dose of 2000 mg/kg bw. Therefore the submission item should be regarded as not acute toxic by dermal route.

Justification for selection of acute toxicity – oral endpoint
The study of Gabriel (1974, Biosearch Report on Acute Oral Toxicity - Rats) represents the only available experimental data.

Justification for selection of acute toxicity – dermal endpoint
The study of Sanders (2012, Harlan Report no. 41103266) represents the only available experimental data.

Justification for classification or non-classification

Based on the available data, the submission item is not classified.