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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guidelines but was conducted according to GLPs and the report contains sufficient data for interpretation of study results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Report does not specifically state that it followed a guideline but method used suggests that it is equivalent or similar to OECD 401.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-isopropylhydroxylamine
EC Number:
225-791-1
EC Name:
N-isopropylhydroxylamine
Cas Number:
5080-22-8
Molecular formula:
C3H9NO
IUPAC Name:
N-(propan-2-yl)hydroxylamine
Details on test material:
Test material identified as N-Isopropylhydroxylamine. No additional information available.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Young adult male and female Sprague-Dawley rats were obtained from Charles River Breeding Laboratories, lnc., Wilminton, MA for use in this study.
All housing and care conformed to the standards established in the "Guide for the Care ane Use of Laboratory Animals" DHEW," Publication No. (NIH)
85-23. Animals were individually housed in wire mesh bottom cages in environment-controlled rooms and provided NIH O7 Open Formula, certified feed (Zeigler Brothers, lnc., Gardners, Ph) and water ad libitum. After an acclimation period of at least 5 days, animals were assigned to the test. Animals were examinee daily during acclimation to assure their suitability as test animals.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Based on the results of the trial test; one dose level at 5.0. g/kg body weight administered to each of ten rats it was decided to define the LC50 value. A range finding study was conducted to deterrnine dose level s for the main study . On the first day of the study, animals received a single oral dose by gavage of the test article administered at a constant concentration.
Doses:
For the Trial Test, groups of 5 males and 5 females were dosed with 5000 mg/kg.

For the Range Finding Study, groups of two males and two females were dosed with 250, 484, 935, 1809 and 3500 mg/kg.

For the definitive LC50 study, groups of 5 male and 5 female rats were dosed with 1500, 2027, 2739, 3700 and 5000 mg/kg.
No. of animals per sex per dose:
5 males and 5 females for the definitive LC50 study.
Control animals:
not specified
Details on study design:
For the definitive LD50 study, groups of 5 males and 5 females were dosed orally with specified doses of test material. All animals were observed for 14 days after dosing. Rats were observed daily during the 14 day observation period. All survivng rats were weighed on day 1, 8 and 15 (with day 1 being the day of dosing). All animals that died during the observation period as well as animals that survived the 14 day observation period were subjected to a gross pathologic examination.
Statistics:
The LD50 values with 95% confidence limits and the slopes of the response curves were calculated using probit analysis (Finney, D.J., Statistical Methods in Biological Assay, secone edition. London: Griffin Press, 1971) when possible, otherwise an alternative acceptable method will be used and documented.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 356 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 887 - <= 2 825
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 942 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 560 - <= 2 315
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 189 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 871 - <= 2 507
Mortality:
Trial Test (5000 mg/kg): all animals died one day after dosing.

In the Range Finding Study, two of four rats (sex not specified) died on the first day after dosing. No other deaths were observed over an 8 day observation period at dose levels ranging from 250 -3500 mg/kg.

In the Definitive LD50 study, 5 of 5 male rats dosed with 3700 or 5000 mg/kg died on day 1 or 2 after dosing. At 2739 mg/kg, 4 of 5 male rats died on day 2 after dosing. At 2027 mg/kg, one of 5 male rats died two days after dosing. All male animals in the 1500 mg/kg group survived the 14 day obseration period. In the same study 5 of 5 female rats dosed at 2739, 3700 or 5000 mg/kg died on day 1 or 2 after dosing. At 2027 mg/kg, four of 5 female rats died on day 2 post dosing. At 1500 mg/kg, all female rats survived the 14 day observation period.
Clinical signs:
other: In the definitive LD50 study, ataxia, decreased activity and increased respiratory rate were the most common clinical observations. Others included salivation, lacrimation, wet abdomen and dark material around the nose. Similar response was noted at hig
Gross pathology:
In the lowest dose level were most of the animals died during the observation period, 2027 and 2739 mg/kg, dark red areas or spots of the lung were the most common observation upon gross necropsy examination. Similar findings were made at higher doses,

There were no noteworthy findings in the 1500 mg/kg group of male or female rats.
Other findings:
No additional information available.

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Conclusions:
The LD50 for male rats was calculated to be 2356 mg/kg body weight with a 95% confidence interval of 1887 to 2825 mg/kg. The LD50 for females was calculated to be 1942 mg/kg with a 95% confidence interval of 1569 to 2315 mg/kg and the combined response was calculated to be 2189 mg/kg with a 95% confidence interval of 1871 to 2507 mg/kg.
Executive summary:

The purpose of this study was to determine the acute oral LD50 of N-Isopropylhydroxylamine following administration by gavage to male and female Sprague-Dawley rats.

The LD50 for male rats was calculated to be 2356 mg/kg body weight with a 95% confidence interval of 1887 to 2825 mg/kg. The LD50 for females was calculated to be 1942 mg/kg with a 95% confidence interval of 1569 to 2315 mg/kg and the combined response was calculated to be 2189 mg/kg with a 95% confidence interval of 1871 to 2507 mg/kg.

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