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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class 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:

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 start of administration: approx. 8 weeks
- Weight at study initiation: At start of administration: 169 - 184 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): 12 to 18-fold air change per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 18, 2012 To: August 7, 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.22 mL/kg bw

DOSAGE PREPARATION (if unusual):
Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was used as supplied. The administration volume was 4.22 mL/kg bw for a dose of 2000 mg/kg bw as the density of the test item was 1.14 g/mL and a correction factor of 2.41 was employed in order to correct for a content of the solid material of 41.5% only.
The pH value of the supplied test item was 6.4.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.

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:

6

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 surviving 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

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: actual ingested (gavage)

Mortality:

No death was recorded within the test period.

Clinical signs:

other: Under the present test conditions, a single oral 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 did not reveal any signs of toxicity.

Gross pathology:

No pathological changes 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 classification (as LD50 > 2000 mg/kg).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute oral 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 oral administration to 6 female CD/Crl:CD(SD)rats. The test substance dosed by oral gavage at 2000 mg active ingredient/kg bw did not reveal any signs of toxicity. No death was recorded within the 14 days observation period. All animals gained the expected weight throughout the whole study period. No pathological changes were observed at necropsy. The LD₅₀ value was ranked exceeding 2000 mg/kg bw.