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Description of key information

The acute toxicity of N-Isopropylhydroxylamine was examined via the oral and intraperitoneal route.   
The acute oral LD50 of N-Isopropylhydroxylamine following administration by gavage to male and female Sprague-Dawley rats was examined. 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.
The acute intraperitoneal LD50 of N-Isopropylhydroxylamine in ICR mice was examined. Animals were dosed with the test article and the survivors were euthanatized three days later. 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).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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.
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.
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.

No additional information available.

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 189 mg/kg bw
Quality of whole database:
Good

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 April - 3 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP/Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Official Journal of the European Communities, Methods for the Determination of Toxicity and Other Health Effects, Part B.3 (Acute Toxicity Dermal), Commission Regulation (EC) No. 440
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
Young adult (9 weeks)/males 184-188 grams and females 136-147 grams at experimental start. The females assigned to test were nulliparous and non-pregnant. Received from Harlan, Indianapolis, IN on April 12, 2011.
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week. Animal Room Temperature and Relative Humidity Ranges: 20-23°C and 42-66%, respectively. Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 7 days
Feed: Purina Certified Rodent Diet (PMI #5002)
Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Prior to application, the test substance was moistened with deionized water to achieve a dry paste by preparing a 60% w/w mixture. Two thousand mg/kg of body weight of the test substance was then applied evenly over a 2-inch x 3-inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) on each animal. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore™ tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study.

After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed with a 3% soap solution followed by tap water and a clean paper towel to remove any residual test substance.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial) and the skin checked for any abnormalities. Ten healthy naive rats (five males and five females; not previously tested) were selected for test.

Individual doses were calculated based on the initial body weights, taking into account the concentration of the test mixture.

Body Weights
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).

Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Necropsy
All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. The external surface of the body and all orifices, tissues, and organs of the thoracic and abdominal cavities were examined.
Statistics:
No additional information available.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived exposure to the test substance.
Clinical signs:
other: Other than the dermal irritation (erythema) noted at the dose site of two males and two females between Days 1 and 5, there were no other clinical findings recorded for any animal over the course of the observation period.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
No additional information available.

No additional information available.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the single dose acute dermal LD50 of Isopropylhydroxylamine (IPHA) is greater than 2,000 mg/kg of body weight in male and female rats.
Executive summary:

An acute dermal toxicity test was conducted with Fischer 344 rats to determine the potential for Isopropylhydroxylamine (IPHA) to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2,000 mg/kg of body weight in male and female rats.

Two thousand milligrams of the test substance per kilogram of body weight was moistened with distilled water and then applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived exposure to the test substance and gained body weight during the study. Other than the dermal irritation (erythema) noted at the dose site of two males and two females between Days 1 and 5, there were no other clinical findings recorded for any animal over the course of the observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Good

Additional information

Oral

An acute oral LD50 of N-Isopropylhydroxylamine was conducted in 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.

Dermal

An acute dermal toxicity test was conducted with Fischer 344 rats to determine the potential for Isopropylhydroxylamine (IPHA) to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 2,000 mg/kg of body weight in male and female rats.


Justification for selection of acute toxicity – oral endpoint
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.

Justification for selection of acute toxicity – dermal endpoint
GLP/Guideline study

Justification for classification or non-classification

The overall acute oral LD50 for male and females rats was 2189 mg/kg. Therefore, IPHA is not classifiable as to its acute oral toxicity under GHS.

The acute dermal LD 50 is > 2000 mg/kg in male and female rats. Therefore, IPHA is not classifiiable as to its acute dermal toxicity under GHS