Trometamol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 - 11 Jun 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

National GLP Compliance Monitoring Authority, Department of Science & Technology, New Delhi, India

Test material

Test material information

Constituent 1

Reference substance name:

Trometamol

EC Number:

201-064-4

EC Name:

Trometamol

Cas Number:

77-86-1

Molecular formula:

C4H11NO3

IUPAC Name:

2-amino-2-(hydroxymethyl)propane-1,3-diol

Details on test material:

- Name of test material (as cited in study report): Tris Amino Ultra Pure
- Physical state: white crystals
- Analytical purity: 99.9%
- Impurities (identity and concentrations): 0.018% (w/w) water
- Lot/batch No.: XK0731LA1C
- Storage condition of test material: at ambient temperature, 18-36 °C
- Recertification date: 22 Feb 2013
- pH: 10.4 (1% aqueous solution)
- Other: soluble in water

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: in-house bred (Outbred); Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore, India- Age at study initiation: 7-8 months- Weight at study initiation: 2.81-2.95 kg- Housing: the rabbits were housed individually in rabbit cages (approximately L 65 cm x B 65 cm x H 45 cm) with a Noryl shallow cage body and Noryl waste trays. The litter collection trays were changed daily, except on Sundays. The feed hoppers and water bottles were changed weekly. - Diet: rabbit feed (Pranav agro Industries Ltd., Maharashtra, India), ad libitum - Water: deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier (manufactured by Eureka Forbes Ltd., Mumbai, India), ad libitum- Acclimation period: 5-6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 21-23- Humidity (%): 60-67- Air changes (per hr): 12-15- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: 02 Jun 2011 To: 11 Jun 2011

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as the control

Amount / concentration applied:

TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

Single application without washing

Observation period (in vivo):

72 hReading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE- Washing (if done): the treated eye remained unwashed SCORING SYSTEM: Draize scoring systemTOOL USED TO ASSESS SCORE: a hand-slit lamp was used to evaluate the severity of damage at all reading time points; fluorescein was used at the 24-hour reading time point to assess the extent of corneal damage

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 72 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 72 h

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight to moderate redness (score 1-2) and chemosis (score 1-2) was observed from the 1-hour reading time point in 3/3 rabbits (see Table 1). The irritation effects had cleared completely in 2/3 rabbits within 48 hours and in the remaining rabbit within 72 hours. No damage to the iris or cornea was observed at any reading time point.

Other effects:

There was no mortality and no signs of toxicity were observed during the study period. The body weight gains were within the normal ranges during the study period.

Any other information on results incl. tables

Table 1. Individual scores for eye irritation parameters

 

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1	2	0	0
	24	2	2	0	0
	48	2	2	0	0
	72	0	0	0	0
	average	1.33	1.33	0.0	0.0
2	1	1	1	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.33	0.0	0.0
3	1	1	2	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.33	0.0	0.0

 

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

CLP: not classified
DSD: not classified

Executive summary:

The acute eye irritation / corrosion study in rabbits was conducted to evaluate the eye irritation potential of Tris Amino Ultra Pure. Under the conditions of this study, Tris Amino Ultra Pure caused conjunctival irritation in the rabbit eye, which cleared by 72 hours.One hundred mg (0.1g) of the test substance was instilled into the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were gently held together for about one second, in order to minimize loss of the test substance. The right eye of each rabbit remained untreated and served as the reference control. The eyes were evaluated at 1, 24, 48 and 72 hours according to the scale for scoring ocular lesions (DRAIZE, 1977). There were no clinical signs of toxicity or animal deaths. All rabbits appeared healthy and gained body weight throughout the observation period. The test was performed in a stepwise manner. A single rabbit was initially exposed to the test substance. Since the test substance was not corrosive, the study was completed using two additional rabbits.