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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 24, 1985- April 4, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study is well-documented and performed according to generally accepted scientific standards.
GLP compliance:
yes
Test type:
other: Dose range finding followed by a unique dose application.
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3,6-dioxaoctamethylenediamine
EC Number:
213-203-6
EC Name:
3,6-dioxaoctamethylenediamine
Cas Number:
929-59-9
Molecular formula:
C6H16N2O2
IUPAC Name:
3,6-dioxaoctamethylenediamine
Test material form:
liquid
Details on test material:
- Physical state: liquid
- Appearance: colourless liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5601-49-1, J-243

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's rabbitry, Harvey's Lake, Pennsylvania
- Age at study initiation: no data
- Weight at study initiation: 2 - 3 kg
- Fasting period before study: no data
- Housing: rabbits were individually housed in cages sized in accordance with the 'Guide for the Care and Use of Labratory Animals' of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum, Waye Rabbit Ration
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C +/- 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h light/12 h dark

IN-LIFE DATES: From: March 21, 1985 To: April 4, 1985

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal trunk, abraded area.
- % coverage: No less than 20%
- Type of wrap if used: Gauze, followed by a rubber dam and wrapped with an ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wrappings were removed, no washing done.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 8.0 g/kg
- Constant volume or concentration used: yes

Duration of exposure:
24 hrs
Doses:
1, 3, 5 and 8 g/kg (dose range finding study)
8 g/kg (main study)
No. of animals per sex per dose:
1 male, 1 female (dose range finding)
5 males, 5 females (main study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 minutes, 2 and 4 hours, and then twice daly through 14 days.
- Necropsy of survivors performed: yes, sacrificed by CO2 inhalation
- Other examinations performed: clinical signs, body weight, organ weights

Results and discussion

Preliminary study:
A dose-range-finding study was performed, consisting of 4 groups of two rabbits per group, dosed at 1.0, 3.0, 5.0 and 8.0 g/kg. No mortality was observed.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 8 other: g/kg
Based on:
test mat.
Mortality:
3 out of 10 rabbits died during the study
Clinical signs:
Decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal stance, dypsnea, poor grooming, necrosis and alopecia at the application site, bruxism, red exudate (anal-genital region) and prostration.
Body weight:
All animals showed apparent weight loss over the course of the study.
Gross pathology:
Necropsy of rabbits dying on study revealed hemorrhages of fascia underlying application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder. Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying application site.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the study, the estimated LD50 of the test material was determined to be greater than 8.0 g/kg. Therefore, the test substance is considered not to be classified according to CLP regulation .
Executive summary:

In a dose-range-finding screen, four groups of two abraded rabbits per group (one male and one female) were administered the test article at 1.0 / 3.0 / 5.0 and 8.0 mg/kg. None of the rabbits died in the dose-range-finding study.

In an 8.0 mg/kg limit test, one group of ten rabbits (five males and five females) was dermally administered the test article.

Three of the animals died during the study. Signs observed included: decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal gait, abnormal stance, dyspnea, poor grooming, necrosis and alopecia at the applicatio site, bruxism, red exudate (anal-genital region) and prostration.

Necropsy of the animals dying on study revealed hemorrhages of fascia underlying the application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder.

Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying the application site.

Based upon the observations made in the definitive acute dermal toxicity study in rabbits, the estimated LD50 for the test article was determined to be greater than 8.0 mg/kg.