Disodium (Z)-4-(9-octadecenylamino)-4-oxo-2(or 3)-sulphonatobutyrate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was not performed under GLP,however the study was conducted according to standards of that time, therefore the study is considered to be adequate, reliable and relevant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: “Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics”, by the Staff of the Division of Pharmacology, FDA (1959)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts

IUPAC Name:

Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): Steinamat B 1003.
- Physical state: White, opaque, viscous substance
- Analytical purity: 35%
- Impurities (identity and concentrations): See confidential details
- Composition of test material, percentage of components: See confidential details
- Purity test date: Not provided
- Lot/batch No.: Not provided
- Expiration date of the lot/batch: Not provided
- Stability under test conditions: Not provided
- Storage condition of test material: Not provided
- Other: pH 10.5

Test animals

Species:

rat

Strain:

other: SPF Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn)
- Age at study initiation: Not provided
- Weight at study initiation: 110- 170g
- Fasting period before study: 16 hours
- Housing: Individual cages
- Diet (e.g. ad libitum): Ssniff/Intermast ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 45-55%
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: Not provided

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

35% watery solution

Doses:

6.30 mL/kg (2205 mg act.ingr./kg bw)
7.94 mL/kg (2779 mg act.ingr./kg bw)
10.0 mL/kg (3500 mg act.ingr./kg bw)
12.60 mL/kg (4410 mg act.ingr./kg bw)
15.90 mL/kg (5565 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: daily
-Frequency of weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

After Litchfiel & Wilcoxon, in conjunction with the Gaussian integral

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

10.4 mL/kg bw

Based on:

test mat.

Remarks:

35% watery solution

Remarks on result:

other: at 48h and 7 days

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3.64 other: g/kg bw

Based on:

act. ingr.

Remarks on result:

other: at 48 hours and 7 days

Mortality:

Mortalities occurred within 48h after application. (See Table 1)

Clinical signs:

other: The test substance evoked at the tested doses, an increasing degree of activity reduction, incoordination, diarrhea and piloerection. In the highest dose, animals also showed abnormalities in position and posture and decreased reflexive excitability. The

Gross pathology:

At necropsy, in the acute mortality group, strong reddened gastric and intestinal mucosa was found. At necropsy, in the group of animals killed at the end of testing, no pathological changes were found in skull, chest and abdominal cavity.

Any other information on results incl. tables

Table 1. Mortality

Group	Dose	24 hours	48 hours	14 days
I	6.30 mL/kg	0/10	0/10	0/10
II	7.94 mL/kg	2/10	2/10	2/10
III	10.00 mL/kg	2/10	4/10	4/10
IV	12.60 mL/kg	8/10	8/10	8/10
V	15.90 mL/kg	10/10	10/10	10/10

 

Table 2. Mean Body weight

Group	Initial body weight	Body weight after 14 days
I	137.5 g	173.0 g
II	142.0 g	168.8 g
III	143.5 g	180.0 g
IV	132.0 g	170.0 g
V	161.5 g	--

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance (35% act.ingr.) was undiluted subjected to an acute toxicity test after single oral application in rats. Under the described experimental conditions the following was found:
1. The 24h-LD50 could be determined as 10.6 mL/kg. The 48 h- LD50 was calculated as 10.4 mL/kg (corresponding to 3640 mg act.ingr./kg bw) and corresponded with the 7d- LD50 because no late mortalities occurred.
2. The fluctuation of the acute toxicity was well delineated due to the slope factor S.

Executive summary:

The test item (35% aqueous solution) was administered to 5 groups of SPF-Wistar rats (5 males and 5 females/group) at doses of 6.3, 7.94, 10.00, 12.60 and 15.90 mL/kg bw. Mortalities occurred within 48h after application. The test substance evoked at the tested doses, an increasing degree of activity reduction, incoordination, diarrhea and piloerection. In the highest dose, animals also showed abnormalities in position and posture and decreased reflexive excitability. The symptoms occurred within 1 hour after application and held on for 24 hours . Thereafter, all surviving animals, showed normal behavior during the entire observation period. At the end of the 14 days observation period all surviving animals showed normal body weight gain rates. At necropsy , in the acute mortality group, strong reddened gastric and intestinal mucosa was found. At necropsy, in the group of animals killed at the end of testing, no pathological changes were found in skull, chest and abdominal cavity. The acute oral LD₅₀was 3640 mg act. ingr./kg bw.