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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-10-23 - 2007-12-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (limit dose at 200 mg/kg bw)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted February 24, 1987
Deviations:
yes
Remarks:
limit dose at 200 mg/kg bw
GLP compliance:
yes
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): N4 Amine
- Physical state: clear liquid
- Analytical purity: 83.4% Bis-APEDA, 12.2% APEDA, 4.4% Tri-APEDA
- Lot/batch No.: 21000-15-1
- Storage condition of test material: room temperature and humidity

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: from Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: not specified
- Weight at study initiation: 2.1 – 2.4 kg for males and females (Table 1)
- Fasting period before study: approx. 90 days
- Housing: 1/cage in suspended wire cages
- Diet: Fresh PMI Rabbit Chow (Diet #5321); ad libitum
- Water: drinking water; ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, and was kept clean and vermin free.
No further details provided
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 2007-11-01 To: 2007-11-15

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk of each animal clipped free of hair
- % coverage: approximately 10% of the body surface
- Type of wrap if used: the test substance was applied a 4-ply porous dressing (10 cm x 15 cm) and wrapped with plastic in a semi-occlusive manner and was secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test article was removed by gently washing with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200 mg/kg bw
Duration of exposure:
24 hours
Doses:
200 mg/kg bw
No. of animals per sex per dose:
2 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed 1, 2 and 4 hours post-dose and once dose daily for toxicity and pharmacological effects, and twice daily for mortality. Body weights were recorded pretest, weekly and at termination.
- Necropsy of survivors performed: yes; all animals were humanely sacrificed using CO2 following study termination and examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination.
- Other examinations performed: clinical signs, body weight, organ weights.
The test sites were scored for dermal irritation at 24 hours post-dose and on days 11 and 14 using the numerical Draize scoring system. The skin was also evaluated evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.
Statistics:
An estimate of the LD50 was made based on the mortality during the study.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality or adverse systemic effects were observed at this unique dose level.
Mortality:
All animals survived the 200 mg/kg bw dermal application.
Clinical signs:
One animal appeared lethargic on the day of treatment (Day 0). There were no abnormal clinical signs noted during the observation period.
Body weight:
Body weight changes were normal (Table 1).
Gross pathology:
Necropsy results revealed abnormalities of the treated skin. No further effects were noted.
Other findings:
Dermal effects were severe at the 24 hours and on days 11 and 14 (Table 2).

Any other information on results incl. tables

Table 1: Body weights

Animal number

Sex

Body weight (kg)

Day 0

Day 7

Day 14

H505

Male

2.5

2.6

2.7

H507

Male

2.4

2.6

2.8

H529

Female

2.9

2.9

3.0

H534

Female

3.0

3.0

3.2

H533

Female

2.2

2.4

2.6

 

Table 2: Dermal observations at indicated time points

Animal number

24 hours

Day 11

Day 14

% remaining 24 hours

Erythema

Edema

Erythema

Edema

Erythema

Edema

H506

>4n,b

3

>4n

1

>4n

1

50%

H508

>4n,b,p

3

>4n,f

2

>4n,s

2

50%

H509

>4n,b,p

3

>4n,f

2

>4n,f

2

50%

H530

>4n,b

3

>4n

2

>4n

1

50%

H533

>4n,b,p

3

>4n,f

1

>4n

1

50%

% remaining = a visual estimate of the amount of material on the skin and gauze at 24 hours, after the wrapping was removed; b = brown areas; f = flaking skin; p = pale areas; s = shiny areas; >4n = necrosis.

 

Applicant's summary and conclusion