Butanedioic acid, 2-sulfo-, mono(C16-18 and C18-unsatd. alkyl) esters, ammonium sodium salts

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test was conducted according to GLP and valid test methods, therefore it is considered relevant, adaquate and reliable for classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Butanedioic acid,sulfo-, mono (C16-18 and C18-unsatd. alkyl) ester, ammonium sodium salt

EC Number:

604-617-1

Cas Number:

147993-66-6

IUPAC Name:

Butanedioic acid,sulfo-, mono (C16-18 and C18-unsatd. alkyl) ester, ammonium sodium salt

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Butanedioic acid, sulfo-, mono (C16-C18 and C18-unsaturated alkyl)esters, ammonium sodium salts; Sulfosuccinic (FA C16-C18/18:1)monoE, Na/NH4
- Physical state: Solid, slight yellow
- Analytical purity: 95.8% (correction factor: 1.04)
- Impurities (identity and concentrations): See confidential details
- Composition of test material, percentage of components: See confidential details
- Purity test date: September 27, 2012
- Lot/batch No.: PURS2012004-01
- Expiration date of the lot/batch: February 9, 2014
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature
- Other: manufacturer/supplier: Pulcra Chemicals GmbH, Isardamm 79-83, 82538 Geretried, Germany

Test animals

Species:

rat

Strain:

other: CD / Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories GmbH, Sandhofer Weg 7, 97633 Sulzfeld,Germany
- Age at dosing: Approx. 8 weeks
- Weight at dosing: Males: 252 - 272 g; Females: 235 – 249 g
- Fasting period before study: Approx. 16 hours before administration; only tap water will be then available ad libitum.
- Housing: During the 14-day observation period the animals were kept singly in MAKROLON cages (type III plus). Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
- Diet (e.g. ad libitum): ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany) ad libitum. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum.
- Acclimation period: 7 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maximum range)
- Humidity (%): 55% ± 15% (maximum range).
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: November 19, 2012 To: December 11, 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Remarks:

aqua ad iniectabilia

Details on dermal exposure:

TEST SITE
- Area of exposure: The intact dorsal skin of the animals was shaved free of hair with a shaver without causing injury approximately 24 hours before application. The site was situated on the animals back between the fore and hind extremities and had an area of at least 5 cm x 6 cm.
- % coverage: approx. 10% (1/10 of body surface)
- Type of wrap if used: The test patch was occlusive. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster on the application site for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes. At the end of the exposure period, possible residual test item was removed where practicable using water or some other appropriate method of cleaning the skin.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg active ingredient/kg bw
- For solids, paste formed: yes. 7011 mg Butanedioic acid, sulfo-, mono (C16-18 and C18-unsatd. alkyl)esters, ammonium sodium salts was moistened with 3505 mg aqua ad iniectabilia. Thereof 3120 mg/kg bw was applied. A correction factor of 1.04 was used.

Duration of exposure:

24 hours

Doses:

2000 mg act. ingr./kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days.
During the follow-up period (2 weeks) changes in skin and fur, eyes and mucous membranes, and the respiratory, circulatory, autonomic and central ner¬vous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma..
Observations on deaths were made at least once daily to minimize loss of animals during the study. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes. At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded. No histopathology was carried out as no macroscopical findings were noted at necropsy.
- Other examinations performed: clinical signs, body weight, other: The skin was observed for the development of erythema and oedema .

Statistics:

The LD50 could not be calculated as no animal died prematurely.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

None of the animals died prematurely.

Clinical signs:

other: No signs of toxicity were observed. A very slight erythema (barely perceptible) on the application site was observed in 5 of 5 male and 5 of 5 female animals on test days 2, 3 and 4.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions the test item containing 95.8% active ingredient requires no labeling (as LD50 > 2000 mg/kg bw).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test item is not classified for acute dermal toxicity.

Executive summary:

Test item containing 95.8% active ingredient was tested in a acute dermal toxicity study. A single dermal administration of 2000 mg act.ingr. /kg bw to 5 male and 5 female CD rats for 24 hours under an occlusive patch,revealed no signs of toxicity and no deaths. A very slight erythema (barely perceptible) on the application site was observed in 5 of 5 male and 5 of 5 female animals on test days 2, 3 and 4. All animals gained the expected body weight throughout the whole experimental period.

According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions the test item containing 95.8% active ingredient requires no labeling (as LD50 > 2000 mg/kg bw).

Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test item is not classified for acute dermal toxicity.