Butanoic acid, 4-amino-4-oxosulfo-, N-coco alkyl derivs., monosodium salts, compds. with triethanolamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26th July - 13th September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butanoic acid, 4-amino-4-oxosulfo-, N-coco alkyl derivs., monosodium salts, compds. with triethanolamine

EC Number:

308-662-5

EC Name:

Butanoic acid, 4-amino-4-oxosulfo-, N-coco alkyl derivs., monosodium salts, compds. with triethanolamine

Cas Number:

98171-53-0

IUPAC Name:

Butanoic acid, 4-amino-4-oxosulfo-, N-coco alkyl derivs., monosodium salts, compds. with triethanolamine

Test material form:

solid

Details on test material:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 0015567151
- Expiration date of the lot/batch: 11 March 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 0015567151
- Expiration date of the lot/batch: January 11, 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item preparation for each test group was produced shortly before administration by stirring with a magnetic stirrer. The homogeneity of the test item preparation duringadministration was ensured by stirring with a magnetic stirrer.

FORM AS APPLIED IN THE TEST (if different from that of starting material): suspension in deionized water

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 10 weeks
- Weight at study initiation: 170 -180 g, Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing, Makrolon cage, type III
- Diet (e.g. ad libitum): feed was withdrawn from the animals at least 16 hours before administration, ad libitum
- Water (e.g. ad libitum): water was available ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30 – 70% relative humidity
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

IN-LIFE DATES: From: July 26, 2017 To: September 12, 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Aqueous preparation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen.

Doses:

2000 mg/kg (first step)
2000 mg/kg (second step)

No. of animals per sex per dose:

3 females per dose and step

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- observations: several times on the day of administration and at least once during each workday thereafter
- weighing: shortly before administration (day 0), weekly thereafter, on the last day of observation and on the day of death or sacrifice moribund starting with study day 1
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: First Step (2000 mg/kg): 1 dead animal Second Step (2000 mg/kg): no mortality observed

Mortality:

One animal in the first 2000 mg/kg bw test group died on day 1 after administration. No mortality occurred in the second 2000 mg/kg bw test group. See Table 1.

Clinical signs:

other: Clinical signs in the first 2000 mg/kg bw test group revealed in all animals impaired general state and piloerection from hour 2 until hour 5, day 1 or day 6 after administration, respectively. Cowering position was seen in two animals from hour 4 until h

Gross pathology:

There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (5 females).

Any other information on results incl. tables

Table 1: Mortality

Mortality
Dose (mg/kg bw):	2000	2000
Sex:	female	female
Administration:	1	2
No. of animals:	3	3
Mortality (animals):	1	No mortality

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the test material (solvent free) (preparations in deionized water) were administered by gavage to two test groups of three fasted Wistar rats each (6 females).  

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 6 days after administration:  

2000 mg/kg (first test group):

- Mortality in one animal

- Impaired general state in all animals

- Cowering position in two animals

- Piloerection in all animals

- Reduced defecation in one animal  

- Macroscopic pathological findings in the animal that died:

- Advanced putrefaction

- Red discoloration of the stomach and intestine

- Dark discoloration of the liver and spleen

2000 mg/kg (second test group):

- No mortality occurred

- Impaired general state in all animals

- Cowering position in all animals

- Piloerection in all animals  

The body weights of the surviving animals (5 females) increased within the normal range throughout the study period.    

There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (5 females).  

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.