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

Endpoint summary

Description of key information

The test material is considered to be not acute toxic by the oral route in the OECD 423 study. The LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw and 1/6 animals died.

The test material is considered to be not acute toxic by the dermal route in the OECD 402 study. The acute dermal median lethal dose was determined to be LD50, dermal, rat > 2000 mg/kg bw. No mortality occured and neither signs of systemic toxicity nor local skin effects were observed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

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.

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).

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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 conditions: Room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed.

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

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

male/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: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: 200-300 g, ± 20% of the mean weight
- Housing: Makrolon cage, type III, single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: 21th August 2017 To: 5th September 2017

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionized water

Details on dermal exposure:

TEST SITE
- Area of exposure: 40 cm²
- % coverage: 10
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze and stretch bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.67 mL/kg bw
- Concentration (if solution): 30 g/100 mL
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

No mortality observed. See table 1.

Clinical signs:

other: Neither signs of systemic toxicity nor local skin effects were observed

Gross pathology:

No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males, and 5 females).

Table 1:  Mortality

Mortality
Dose (mg/kg bw):	2000	2000
Sex:	male	female
Application:	1	1
No. of animals:	5	5
Mortality (animals):	No mortality	No mortality

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of test material (solvent free) after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of test material (solvent free) (as suspension in deionized water). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

- No mortality occurred.

- Neither signs of systemic toxicity nor local skin effects were observed

- The body weight of all five males and one female animal increased within the normal range throughout the study period. Four female animals showed stagnation or marginal loss of body weight during the first week, but they gained weight in a normal range during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.

- No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males, and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Acute oral

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 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.

Acute dermal

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of test material (solvent free) (as suspension in deionized water). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

- No mortality occurred.

- Neither signs of systemic toxicity nor local skin effects were observed

- The body weight of all five males and one female animal increased within the normal range throughout the study period. Four female animals showed stagnation or marginal loss of body weight during the first week, but they gained weight in a normal range during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.

- No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males, and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity (oral and dermal) under Regulation (EC) No. 1272/2008.