N-isopropylhydroxylamine

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

9-12 January 1990

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:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The objective of this in vivo assay was to determine the dose range of the test article, NIPHA, to be used in a subsequent acute in vivo bone marrow micronucleus assay. Toxicity and/or mortalities were assessed in ICR mice. The test article was suspended in 0.9% saline and dosed by intraperitoneal injection at 250, 500, 875, 1250, and 1625 mg/kg body weight. Animals were dosed with the test article and the survivors were euthanatized three days later. Six animals (three males and three females) were randomly assigned to each dose group.

GLP compliance:

yes

Test material

Test material information

Constituent 1

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:

NIPHA, N-isopropylhydroxylamine
(Lot #14422-83-1S)

Test animals

Species:

mouse

Strain:

ICR

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

physiological saline

Doses:

Solubility and Stability
The test article, NIPHA, was supplied in the form of white crystals. The soluhility of the test article was evaluated in deionized water and 0.9% saline. Sterile saline (0.9%, Abbott Lot 115-117-DM-03, Exp. 4/1/90) was selected as the vehicle to be used in the assay. In the solubility test 663.4 mg of NIPHA was added to 2.0 ml of 0.9% saline which resulted in a clear colorless solution with a final volume of --2.4 ml and a final calculated concentration of about 276.4 mg/ml. The stability of the test article under the preparation and dosing conditions of the assay is the responsibility of the sponsor.

Dose Selection
The dose levels used in the assay were 250, 500, 875, 1250, and 1625 mg/kg body weight and were administered by intraperitoneal injection. Initial dose levels of 500, 1625, 2750, 3875, and 5000 mg/kg were selected based upon the lack of any available toxicity data for the test article. These dose levels were reassigned by the study director at the time of dosing when immediate toxicity was observed at the 1625 mg/kg dose level. The route of administration used in this assay was specified by the sponsor.

Dosing Information
The animals used in the assay were dosed on Tuesday, January 9, 1990. The weight range of the animals used in the dose range finding assay was 27.0 - 35.6 grams and 24.5 - 29.7 grams for the males and females, respectively. Dosing solutions were prepared just prior to dosing. A 250 mg/ml stock solution was prepared by adding 17 ml of 0.9% saline to 5.5006 grams of NIPHA for a final calculated concentration of 250 mg/ml. All dose levels were prepared by making dilutions of this stock solution. An outline of the dosing scheme is found in the table below.

No. of animals per sex per dose:

3 males/sex/dose level

Control animals:

not specified

Results and discussion

Any other information on results incl. tables

All animals were examined after dosing and periodically throughout the duration of the study (three days) for toxic effects and/or mortalities. Five to seven minutes after dosing two animals of each sex in the 1625 mg/kg dose group had died. The surviving female was languid and the surviving male was prostrate with polypnea. All other animals in the other dose groups with the exception of those in the 250 mg/kg group were slightly languid after dosing. Those animals in the 250 mg/kg group appeared normal and healthy after dosing. On the day after dosing all surviving animals had recovered and for the duration of the study, appeared normal and healthy.

Table 1. Summary of Mortalities Within 3 Days in Mice Dosed Acutely with RIPHA

	Observations
Treatment	Males	Females
250 mg/kg	0/3	0/3
500 mg/kg	0/3	0/3
875 mg/kg	0/3	0/3
1250 mg/kg	0/3	0/3
1625 mg/kg	2/3	2/3

Applicant's summary and conclusion

Conclusions:

Based upon the mortality data from this study the LDso was calculated by probit analysis (Finney, 1971), for the males and females combined to be 1605 mg/kg (95% confidence limits could not be calculated). The results of this range finding assay were sufficient to select doses for a mouse bone marrow micronucleus assay.

Executive summary:

The objective of this in vivo assay was to determine the dose range of the test article, NIPHA, to be used in a subsequent acute in vivo bone marrow micronucleus assay. Toxicity and/or mortalities were assessed in ICR mice. The test article was suspended in 0.9% saline and dosed by intraperitoneal injection at 250, 500, 875, 1250, and 1625 mg/kg body weight. Animals were dosed with the test article and the survivors were euthanatized three days later. Six animals (three males and three females) were randomly assigned to each dose group. Based upon the mortality data from this study the LD₅₀ was calculated for the males and females combined to be 1605 mg/kg (95% confidence limits could not be calculated).