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

Acute Toxicity: dermal

Administrative data

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

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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

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:

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 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

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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).

Any other information on results incl. tables

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

Applicant's summary and conclusion

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