1-ethyl-3-methyl-3H-imidazolium dicyanidoamide(1-)

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Test Guideline of 12 Nosan No. 8147

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay, Labor für biologische Analytik GmbH, 69120 Heidelberg

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-ethyl-1-methyl-1H-Imidazolium salt with N-cyanocyanamide (1:1)

EC Number:

609-330-5

Cas Number:

370865-89-7

Molecular formula:

C6 H11 N2 .C2 N3

IUPAC Name:

3-ethyl-1-methyl-1H-Imidazolium salt with N-cyanocyanamide (1:1)

Specific details on test material used for the study:

- Name of test material (as cited in study report): EMIM Dicyanamid
- Test item No.: 12/0071-2
- Batch identification: 0013141983
- Content: 97.4 g/100 g determined by 1H-NMR spectroscopy
- Homogeneity: the test item was homogeneous by visual inspection
- Storage stability: the stability of the test item under storage conditions over the study period was guaranteed by the sponsor
- Expiry date: February 19, 2017
- Storage conditions: room temperature, under N2
- Physical state / color: liquid / colorless to brown, clear

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 nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: males: 222 - 242 g; females: 207 - 215 g
- Housing: single housing in Makrolon cages type III, including bedding (H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany) and enrichment (Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria)
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: tap water ad libitum
- Acclimation period: acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 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.)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE/EXPOSURE
- Clipping of the fur: about 24 hours before application
- Route of application: single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing (the test item was covered with an air-permeable dressing; 4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG) for 24 hours. Afterwards removal of the semi-occlusive dressing, rinsing of the application site with warm water.
- Application area: about 40 cm² (corresponds to at least 10% of the body surface)
- Time of day of application: in the morning

TEST MATERIAL
- Amount(s) applied: 1.80 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Observation period: 14 days
- Body weight determination: individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
- 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.
- Mortality: a check for any dead or moribund animals was made at least once each workday.
- Pathology: necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
- Assessment of skin reactions: the evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59. Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.

Statistics:

Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

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:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred.

Clinical signs:

other: No systemic clinical signs or local effects were observed during clinical examination.

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