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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12th February 1996 to 5th March 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline cited only partially followed and study claims no compliance that it was conducted to the principles of Good Laboratory Practice.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
partial claim only
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-Methyloctane-1,8-diamine
EC Number:
700-111-0
Cas Number:
148528-05-6
Molecular formula:
C9H22N2
IUPAC Name:
2-Methyloctane-1,8-diamine
Details on test material:
- Name of test material (as cited in study report): 2-Methyl-1,8-octanediamine
- Substance type: technical material
- Physical state: colourless liquid
- Analytical purity: > 99%
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Isomers composition: N/A
- Purity test date: Not reported
- Lot/batch No.: Not reported
- Expiration date of the lot/batch: Not reported
- Stability under test conditions: Not reported
- Storage condition of test material: not reported
- Other:

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hino Breeding Center, Charles River, Japan.
- Age at study initiation: 6 weeks (arrived at 5 weeks of age but acclimatised for 8 days prior to study start)
- Weight at study initiation: Not reported
- Fasting period before study: overnight prior to dosing
- Housing: 5/cage in polycarbonate solid-floored cages with wood flakes (White Flake (TM), Oriental Yeast Co., Ltd)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 45 - 65%
- Air changes (per hr): ventilated at the rate of 15 times per hour
- Photoperiod (hrs dark / hrs light): 12hours light/12 hours dark


IN-LIFE DATES: From: 12th February 1996 To: 5th March 1996

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12.5, 25, 50 & 100 mg/mL
- Amount of vehicle (if gavage): 0.1 / 10 g of bodyweight
- Justification for choice of vehicle: Not stated
- Lot/batch no. (if required): Not reported
- Purity: Not reported but distilled water used


MAXIMUM DOSE VOLUME APPLIED:
ca. 0.3 ml

DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
vehicle control (0 mg/kg); 125, 250, 500 & 1000mg/kg
No. of animals per sex per dose:
5 males per dose group
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed once in the morning and once in the evening from day of dosing to Day 13; bodyweights
recorded on Day 0 (prior to dosing) and on days 7 & 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic appearence
Statistics:
No statistical analyses waere performed

Results and discussion

Preliminary study:
No preliminary study reported
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 250 - < 1 000 mg/kg bw
Mortality:
100% at 1000 mg/kg; 40% at 500 mg/kg; 0% at 250 mg/kg; 0% at 125 mg/kg; 0% for controls


Clinical signs:
No clinical signs are reported
Body weight:
Bodyweight gain was suppressed at the dose level 500 mg/kg (at the 1000 mg/kg level, all mice had died by Day 1.)
Gross pathology:
All 5 mice that died by day 1 in the high level (1000 mg/kg) showed haemorrhage in the stomach and intestine at necropsy and 4 showed whitish
foci on the liver; 2 mice that died at the dose level 500 mg/kg (Days 1 & 2) showed whitish foci on the liver and 1 showed haemorrhage in the
stomach and intestine. There were no abnormal findings in the remaining animals which survived up to Day 14.
Other findings:
- Organ weights: Not recorded
- Histopathology: N/A
- Potential target organs: Not reported
- Other observations: N/A

Any other information on results incl. tables

Mortality of the mice that received the test substance and their macroscopic findings are summarized in Table 2 below. Lethal toxicity to the mice was observed at the doses of 500 and 100 mg/kg in the early period (Day 0-2) after dosing. Haemorrhage in the stomach and intestine was observed in the mice that died on Day 0-1, and whitish foci were found on the liver of the mice that died on Day 1-2. Macroscopic abnormalities were not found in the mice that survived to the end of the study (Day 14).

Bodyweight gain during the study was suppressed at the dose level of 500 mg/kg. Therefore, the acute lethal oral dose (LD50) to mice of the test substance was demonstrated to be greater than 250 and less than 1000 mg/kg in this study.

Table 2.

Mortality after dosing of 2-methyl-1,8-octanediamine and macroscopic organ findings in mice that died during the observation period or killed at study termination

Group

[No. of mice dosed]

Dose (mg/kg)

Mortality data

Organ findings

[No. of mice showed the finding]

% Mortality

A

[5]

1000

A mouse died on Day 0 (the day of dosing)

Haemorrhage in stomach and intestine [1]

100

Four mice died on Day 1

Haemorrhage in stomach and intestine [4]; whitish foci on liver [4]

No mouse survived to Day 14

-

B

[5]

500

A mouse died on Day 1

Haemorrhage in stomach and intestine [1]; whitish foci on liver [1]

40

A mouse died on Day 2

Whitish foci on liver [1]

Three mice survived up to Day 14

No abnormal findings [3]

C

[5]

250

All mice survived to Day 14

No abnormal findings [5]

0

D

[5]

125

All mice survived to Day 14

No abnormal findings [5]

0

E

[5]

0

(vehicle control)

All mice survived to Day 14

No abnormal findings [5]

0

Applicant's summary and conclusion

Conclusions:
When administered orally to male mice, the lethal dose (LD50) of 2-methyl -1,8-octanediamine was found to be greater than 250 and less than 1000 mg/kg.
Executive summary:

A study was conducted by Kuraray Co. Ltd., at their Kurashi Research Laboratories, Japan to evaluate the acute oral toxicity of the substance 2 -methyl-1,8 -octanediame (MODA) to mice. The study was only partially conducted according to OECD Guideline No. 401 and has no claim of compliance to the principles of GLP. However, the study is quite well documented and appears to meet basic scientific principles. Groups of 5 male mice were each given a single oral dose of the substance at dose levels of vehicle only and at 125, 250, 500 or 1000 mg /kg. Lethal toxicity was found at the dose levels of 500 and 1000 mg/kg. A decrease in bodyweight gain was observed in the mice dosed at 500 mg/kg. No abnormalities were found in the mice dosed at 125 or 250 mg/kg throughout the study. The acute lethal oral dose (LD50) of the test substance was estimated to be greater than 250 and less than 1000 mg/kg.

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