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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guidelineopen allclose all
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

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:
Isopropylhydroxylamine (IPHA), Lot #: CEC-201002707-61
Area percent purity was 99.7% based on GC analysis. Sample also contained 0.23 weight % water by coulometric Karl Fischer titration.
Structural confirmation of the major component was confirmed by nuclear magnetic resonance and mass spectrometry.

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels
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.

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

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.

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