C18 unsaturated fatty acids, reaction products with 1-aminopropan-2-ol, maleic anhydride and sodium bisulfite

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:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

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, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-18(even numbered) and C18 unsaturated)alkyl)amino]ethyl]esters, disodium salts

IUPAC Name:

Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-18(even numbered) and C18 unsaturated)alkyl)amino]ethyl]esters, disodium salts

Test material form:

other: liquid

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, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: At dosing: Males: approx. 8 weeks; Females: Approx. 9 weeks
- Weight at study initiation: At dosing: Males: 215 - 237 g; Females: 217 – 239 g
- Fasting period before study: Approx. 16 hours before administration (only tap water was then available ad libitum)
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages ( type III plus) . Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany)
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum.
- Acclimation period: At least 5 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: July 18, 2012 To: August 6, 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: The shaved intact dorsal skin, between the fore and hind extremities
- % coverage: 5 cm x 6 cm, approx. 1/10 of body surface
- Type of wrap if used: 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 strips (Omniplast (P. HARTMANN AG, 89522 Heidenheim, Germany) on the application site for 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit) 4.22 mL/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

1 dose group (Limit test): 2000 mg/kg bw (dose level refers to the solids ingredients of the test item)

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: 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. 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
- Other examinations performed: clinical signs (changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern; tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma), body weight, gross pathology

Results and discussion

Effect levels

Key result

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: Under the present test conditions, a single dermal administration of 2000 mg Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts/kg bw to rats revealed no signs of toxicity.

Gross pathology:

No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

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,Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts requires no labeling (as LD50 > 2000 mg/kg).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute dermal toxicity.

Executive summary:

In this experiment, Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was examined for acute toxicity after a single dermal application to rats. One dose level of 2000 mg/kg bw was administered on the shaved intact dorsal skin, between the fore and hind extremities of 5 male and 5 female CD/Crl:CD(SD) rats. 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 strips on the application site for 24 hours. All animals were observed for a period of 14 days. Under the present test conditions, a single dermal administration of 2000 mg active ingredient/kg bw to rats revealed no signs of toxicity and no deaths. All animals gained the expected body weight throughout the whole experimental period. No macroscopic findings were observed at necropsy.