Propanenitrile, 2-[bis(cyanomethyl)amino]-

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:

other: GLP guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): MGDN
- Substance type: powder
- Physical state: solid
- Analytical purity: 99.5 area-%
- Lot/batch No.: Betriebsware C404
- Stability under test conditions: The stability under storage conditions will be determined by reanalysis.
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: Wistar, HanRcc:WIST(SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services
- Age at study initiation: Young adult animals (male animals approx. 8 – 10 weeks, female animals approx. 12 – 14 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: no data
- Housing: Single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Acclimatization for at least 5 days before application.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 30 – 70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

TEST SITE
- Area of exposure: Single application to the clipped epidermis (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: Covering of the application site with a semi-occlusive dressing (the bandage consists of four
layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG) for 24 hours, afterwards removal of the dressing.


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): 2.86 g/kg bw
- Concentration (if solution): 70 g/100 ml
- Constant volume or concentration used: yes
- For solids, paste formed: yes (suspension)


VEHICLE
- Amount(s) applied (volume or weight with unit): 2.86 g/kg bw
- Concentration (if solution): 70 g/100 ml

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

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 at the end of the study.
Recording of signs and symptoms several times on the day of application, at least once each workday for the individual animals.
A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other:
Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semiocclusive dressing (day 1), as a rule weekly thereafter and at
the end of the study (last day of the observation period).

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no effects observed

Mortality:

No mortality occured.

Clinical signs:

Systemic efects: No systemic clinical observations were observed during clinical examination.
Local effects: No local effects were observed.

Body weight:

The mean body weights of the animals increased throughout the study period.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined at termination of the study.