N-isopropylhydroxylamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1987

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:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Essentially followed the Draize test.

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:

N-Isopropylhydroxylamine, Lot No. 14132-54-1, was used.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Young adult New Zealand,hnite rabbits (Ace Animals, Inc., Boyertown, PAl were acclimated to the FDRL laboratory environment for a minimum of 5 days. They were observed daily during the acclimation period to assure their sui tabU i ty as test animals. All' housing and care conformed to the standards established in "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 85-23. The animals were individually housed in wire-mesh cages. Food (NIH 09 Rabbit Ration, Zeigler Brothers, Inc., Gardners, PA) and fresh tap water were supplied ad libitum. Animals were identified with ear tags and color coded cage cards. Six animals weighing between two and three kilograms were randomly selected from the acclimating animals and assigned to the test group.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: The back of each rabbit was clipped with an electric clipper on the day prior to dosing.

Vehicle:

physiological saline

Remarks:

Applied to the test material following applicaton on rabbit skin.

Controls:

not specified

Amount / concentration applied:

Each rabbit was administered 0.5 g of the test article moistened with 0.5 ml of physio]ogical saline to two non-abraded test sites.

Duration of treatment / exposure:

The binders and collars were removed four hours post-dose administration and the exposure sites gently wiped with gauze to remove as much non-absorbed test article as possible.

Observation period:

Test Site Evaluation
Dermal irritation was evaluated at 4.5, 28, 52 and 76 hours as well as 4, 7 and 10 days post-dose administration. Erythema and edema were scored
separately according to the Draize method.

Observations
The animals were observed daily for mortality and overt pharmacotoxic signs. Body weights were obtained on study day 1, prior to dose . administration. At study termination, the animals were euthanized by intracardiac injection of sodium pentobarbital and discarded.

Number of animals:

6 rabbits

Details on study design:

Dose Administration
The back of each rabbit was clipped with an electric clipper on the day prior to dosing. The test article was topically applied to two non-abraded dorsal test sites per rabbit and moistened with physiological saline. The test sites were wrapped with semi-occlusive binders consisting of a one-inch square gauze patch and Micropore® tape immediately after dosing. The animals were fitted with circular collars during the exposure period to prevent removal of the patches. The binders and collars were removed four hours post-dose administration and the exposure sites gently wiped with gauze to remove as much non-absorbed test article as possible.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal: all

Time point:

other: all timepoints

Score:

0

Max. score:

0

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all animals

Time point:

other: mean across 28/52/76 hrs

Score:

0.9

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean across 28/52/76 hrs

Score:

0

Max. score:

0

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean across 28/52/76 hrs

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 10 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean across 28/52/76 hrs

Score:

0

Results 6

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: mean across 28/52/76 hrs

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 10 days

Results 7

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: mean across 28/52/76 hrs

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 8

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: mean across 28/52/76 hrs

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Dermal irritation was not noted in any animal 4.5 hours post-dose. At 24 hours, four animals exhibited slight erythema. Irritation was still evident at 52, 76 hours and day 4. At day 7, slight erythema was noted in one animal. There was no evidence of edema at any time through the 10 day observation period. All test sites appeared normal at day 10 and the study was terminated.

Other effects:

No overt pharmacotoxic signs were noted in any animal.

Any other information on results incl. tables

Animal number	Scoring	Test site	28 hr	52 hr	76 hr
1	Erythema	left	0	0	0
	Erythema	right	0	0	0
1	Edema	left	0	0	0
	Edema	right	0	0	0
2	Erythema	left	1	1	1
	Erythema	right	1	1	1
	Edema	left	0	0	0
	Edema	right	0	0	0
3	Erythema	left	0	0	0
	Erythema	right	0	0	0
3	Edema	left	0	0	0
	Edema	right	0	0	0
4	Erythema	left	1	1	1
	Erythema	right	1	1	1
4	Edema	left	0	0	0
	Edema	right	0	0	0
5	Erythema	left	1	2	2
	Erythema	right	1	1	1
5	Edema	left	0	0	0
	Edema	right	0	0	0
6	Erythema	left	1	2	2
	Erythema	right	1	1	1
6	Edema	left	0	0	0
	Edema	right	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

N-Isopropylhydroxylamine was slightly irritating to the skin of six New Zealand White rabbits following four-hour, semi-occlusive topical exposure. The mean primary dermal irritation score of the test group was 0.78. All edema scores were 0. Erythema mean scores across all animals and the 28, 52 and 76 hr readings were 0.9. The test sites showed normal by day 10.

Executive summary:

N-Isopropylhydroxylamine was evaluated for potential primary dermal irritation using six New Zealand White rabbits. Each rabbit was administered 0.5 g of the test article moistened with 0.5 ml of physiological saline to two non-abraded test sites. The test sites were semi-occlusively wrapped for four hours following dose administration. Dermal irritation was scored at 4.5, 28, 52 and 76 hours as well as 4, 7 and 10 days post-administration according to the Draize method.

Under the conditions of this study, the mean primary dermal irritation score was 0.78 based on Draize methodolgy. All edema scores were 0. Erythema mean scores across all animals and the 28, 52 and 76 hr readings were 0.9. The test sites showed normal by day 10. According to Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, N-Isopropylhydroxylamine is not classified for skin irritation.