reaction mass of disodium;3-[2-(2-carboxylatoethylamino)-ethylamino]propanoate and sodium 3-[(2-aminoethyl)amino]propanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 7, 2016 - July 29, 2016

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay Labor für biologische Analytik GmbH, 69120 Heidelberg, Germany

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

reaction mass of disodium;3-[2-(2-carboxylatoethylamino)-ethylamino]propanoate and sodium 3-[(2-aminoethyl)amino]propanoate

Molecular formula:

C5H11N2O2Na and C8H14N2O4Na2

IUPAC Name:

reaction mass of disodium;3-[2-(2-carboxylatoethylamino)-ethylamino]propanoate and sodium 3-[(2-aminoethyl)amino]propanoate

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Do_0164
- Expiration date of the lot/batch: May 30, 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, under argon
- Stability under test conditions: guaranteed

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: single housing, Makrolon cage, type III
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

deionized

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: about 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: 4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water

TEST MATERIAL
- Amount(s) applied: 5 mL/kg bw
- Constant volume or concentration used: yes, 40 g/100mL
- For solids, paste formed: no

Duration of exposure:

14 days

Doses:

2000 mg/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 and weighing:
Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed:
Scoring of skin findings:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.

The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity."
Erythema and eschar formation
Grading
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well- defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

Edema formation
Grading
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed during clinical examination. No local effects were observed.

Body weight:

The body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals increased within the normal range throughout the study period with one exception. In one female animal the body weight stagnated during the first week, but the animal 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.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met