N-isopropylhydroxylamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 - 9 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 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

may have used more animals

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Young adult New Zealand White rabbits (Ace Animals Inc., Boyertown, PA) were acclimated to the FDRL laboratory environment for a minimum of 5 days. They were observed daily during the acclimation period to assure their suitability 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. Nine animals weighing between two and three kilograms were randomly selected from the acclimating animals and assigned to either the non-irrigated or irrigated test group (six and three animals, respectively). The eyes of each rabbit were examined with
sodium fluorescein and an ultraviolet lamp on the day prior to dosing to verify the absence of preexisting ocular lesions.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

The test article (0.1 g) was instilled into one eye of each rabbjt.

Duration of treatment / exposure:

The lower eyelid was gently pulled away from the eyeball to form a cup (conjunctival sac) and the test article inserted therein. The lids were then held together for one secotld and released. The treated eye of six animals remajned non-irrigated. The treated eyes of the remaining three animals were thoroughly irrigated with physiological saline beginning thirty seconds after test article instillation.

Observation period (in vivo):

Primary eye irritation was evaluated at 1, 24, 48 and 72 hours post-dose administration. The cornea, iris and conjunctiva were scored separately according to the Draize system (Draize, 1959).

Reference
Draize, J.H., 1959, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, In: Association of Food and Drug Officials in the United States, Austin, Texas.

Number of animals or in vitro replicates:

Nine rabbits were used. The treated eye of six animals remajned non-irrigated. The treated eyes of the remaining three animals were thoroughly irrigated with physiological saline beginning thirty seconds after test article instillation.

Details on study design:

No additional information available.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 24/48/72

Score:

0.28

Max. score:

1

Reversibility:

fully reversible within: 72 hrs

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 24/48/72

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Remarks:

all animals

Time point:

other: 24/48/72

Score:

0.89

Max. score:

2

Reversibility:

fully reversible within: 72 hrs

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 24/48/72

Score:

0.28

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Irritant / corrosive response data:

Non-Irrigated Group:
All animals exhibited slight to moderate conjunctival redness, swelling, blistering and discharge at 1 hour post-dose. Corneal opacity was noted in four of six animals at 24 hours post-dose. These effects were reversible by 72 hours post-dose.
Irrigated Group:
At 1- hour post-dose administration all animals exhibited slight conjunctival redness. In addition, conjunctival swelling, blistering and discharge were noted in two animals. At 24 hours, corneal opacity was noted in two animals. These effects were reversible by 72 hours post-dose administration.

Other effects:

Observations
No overt pharmacotoxic signs were noted in any animal.

Any other information on results incl. tables

Animal Number	Tissue	24 hr	48 hr	72 hr	Comment
1	Corneal opacity	1	0	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	2	1	0	unrinsed
	Conjunctiva chemosis	1	0	0	unrinsed
2	Corneal opacity	1	0	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	2	1	0	unrinsed
	Conjunctiva chemosis	1	0	0	unrinsed
3	Corneal opacity	1	1	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	2	1	0	unrinsed
	Conjunctiva chemosis	1	0	0	unrinsed
4	Corneal opacity	0	0	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	2	1	0	unrinsed
	Conjunctiva chemosis	1	0	0	unrinsed
5	Corneal opacity	0	0	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	1	0	0	unrinsed
	Conjunctiva chemosis	0	0	0	unrinsed
6	Corneal opacity	1	0	0	unrinsed
	Iris	0	0	0	unrinsed
	Conjunctiva redness	2	1	0	unrinsed
	Conjunctiva chemosis	1	0	0	unrinsed
7	Corneal opacity	0	0	0	rinsed 30 seconds after instillation
	Iris	0	0	0	rinsed 30 seconds after instillation
	Conjunctiva redness	1	1	0	rinsed 30 seconds after instillation
	Conjunctiva chemosis	0	0	0	rinsed 30 seconds after instillation
8	Corneal opacity	1	1	0	rinsed 30 seconds after instillation
	Iris	0	0	0	rinsed 30 seconds after instillation
	Conjunctiva redness	2	0	0	rinsed 30 seconds after instillation
	Conjunctiva chemosis	1	0	0	rinsed 30 seconds after instillation
9	Corneal opacity	1	0	0	rinsed 30 seconds after instillation
	Iris	0	0	0	rinsed 30 seconds after instillation
	Conjunctiva redness	1	1	0	rinsed 30 seconds after instillation
	Conjunctiva chemosis	0	0	0	rinsed 30 seconds after instillation

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

N-Isopropylhydroxylamine produced corneal opacity and conjunctival irritation to rabbits' eyes without irrigation. These effects were reversible in both groups by 72 hours post-dose administration. The mean scores across timepoints per animal and across all scores were below the GHS/CLP classification thresholds for all endpoints.

Executive summary:

N-Isopropylhydroxylamine was evaluated for potential primary eye irritation using nine New Zealand White rabbits. Each rabbit was administered 0.1 g of the test article to the conjunctival sac of one eye. The untreated contralateral eye of each rabbit served as a control. The treated eye of three rabbits was irrigated with physiological saline thirty seconds after test article administration.

Treated and untreated eyes were examined at 1, 24, 48 and 72 hours post-administration and ocular irritation scored according to the Draize method.

Under the conditions of this study, N-Isopropylhydroxylamine produced corneal opacity and conjunctival irritation to rabbits' eyes without irrigation. Corneal opacity and conjunctival irritation was produced by N-Isopropylhydroxylamine to the rabbits' eyes irrigated thirty seconds after instillation. These effects were reversible in both groups by 72 hours post-dose administration.

According to Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, the test material would not be classified for eye irritation.