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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 9, 1981 through September 28, 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented GLP study performed according to a method similar to OECD Guideline 401.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4236-43-5, Order #J-85
- Substance type: yellow liquid
- Purity: responsibility of the sponsor. It is confirmed by the Sponsor that the test has been performed with a 50% aqueous solution.
- Stability: There was no apparent change in the physical state of the test article during administration
- Other: Specific gravity = 1.136 g/mL

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Weight at study initiation: 180 - 360 grams after fasting. The weight variation in animals or between groups did not exceed +/- 20%
- Housing: Separate isolation by test system; rats were housed individually in stainless steel wire mesh cages. Size in accordance with Guide for the Care and Use of Laboratory Animals of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): Wayne Lab Blox, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, briding, and scattering
- Water (e.g. ad libitum): Availability - fresh tap water, fit for human consumption, ad libitum, using an automatic watering system supplied by Edstrom Industries Inc., Waterford, Wisconsin
- Acclimation period: Five days
- Fasting period before study: 18 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
7000, 8000, 9000 and 10000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed approximately at one, two, four and twenty-four hours after dosing and twice daily for fourteen days for pharmacotoxic, CNS effects and mortality. On the seventh and fourteenth day body weights were recorded.
- Necropsy of survivors performed: yes: The surviving rats were sacrificed by CO2 inhalation and a gross necropsy performed.
Statistics:
no details

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9 200 mg/kg bw
Based on:
test mat.
95% CL:
8 200 - 10 300
Sex:
male
Dose descriptor:
LD50
Effect level:
9 800 mg/kg bw
Based on:
test mat.
95% CL:
8 800 - 10 900
Sex:
female
Dose descriptor:
LD50
Effect level:
9 300 mg/kg bw
Based on:
test mat.
95% CL:
7 800 - 11 200
Mortality:
None of the animals died at the 7000 mg/kg dose level, two of the ten died at the 8000 mg/kg dose level (2 females), three of ten died at the 9000 mg/kg dose level (1 male, 2 females) and seven of ten died at the 10000 mg/kg dose level (3 males and 4 females).
Clinical signs:
Diarrhea, piloerection, abnormal gait, abnormal stance, decreased body tone, decreased activity and orange discoloration around the nose and genital areas.
Body weight:
No details given.
Gross pathology:
Necropsy revealed distended fluid-filled stomachs and intestines (clear, tan, green, white or orange), mottled lungs, darkened thymuses and darkened lymph nodes. Terminal necropsy revealed no visible lesions in any of the remaining rats.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The calculated acute oral LD50 for male and female rats treated with the substance, was determined to be 9200 mg/kg with 95% confidence limits of 8200 to 10300 mg/kg. The test solution used was a 50% aqueous solution of NMMO. The LD50 of the pure NMMO is therefore considered to be 4600 mg/kg. Based on the study results and the criteria of the CLP Regulation, this substance should not be classified for oral toxicity.