Reaction products of ethylene glycol, urea and paraformaldehyde (EUF)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 19, 2007 to December 19, 2007 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

reaction products of ethylene glycol, urea and paraformaldehyde

EC Number:

700-934-5

Molecular formula:

No exact molecular formula can be given for a complex reaction mixture (UVCB substance).

IUPAC Name:

reaction products of ethylene glycol, urea and paraformaldehyde

Details on test material:

- Name of test material (as cited in study report): TPI 1618
- Substance type: Formaldehyde releaser
- Physical state: Colourless liquid
- Analytical purity: 100%
- Composition of test material, percentage of components: Reaction product of ethylene glycol, urea and paraformaldehyde
- Purity test date: October 25, 2007
- Lot/batch No.: 1118965
- Expiration date of the lot/batch: December 2008
- Storage condition of test material: dry, room temperature

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian, Chbb:HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 88353 Kißleg
- Age at study initiation: 33 - 36 months
- Weight at study initiation: 2.7-2.9 kg
- Housing: Individually in PPO cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (12 hrs dark / 12 hrs light):

IN-LIFE DATES: From November 10, 2007 to December 19, 2007

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: one eye was treated, the other one served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100%

Duration of treatment / exposure:

Exposure was 24 hours. At this time, fluorescein was instilled and irrigated with 20 mL of a 0.9% of sodium chloride solution.

Observation period (in vivo):

21 days; Eye examinations were performed at 1, 24, 48 and72 hours and on Days 7, 14 and 21

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

SCORING SYSTEM: Cornea
A) Opacity degree of density
No ulceration or opacity: 0
Scattered or diffuse area of opacity: 1
Easily discernable translucent areas: 2
Nacreous areas; no details of iris visible: 3
Complete corneal opacity, iris not discernable: 4
B) Extent of effected area
More than 0 but less than ¼: 1
More than ¼ but less than ½: 2
More than ½ but less than ¾: 3
More than ¾ to whole area: 4
Iris
Normal: 0
Markedly deepened folds and/or
congestion, swelling, moderate circumcorneal
injection but still shows (even delayed) reaction: 1
No reaction to light, hemorrhage, gross destruction: 2
Conjunctiva
A) Reddening
Blood vessels normal: 0
Blood vessels definitely injected: 1
Diffuse crimson red, individual vessels not
easily discernible: 2
Diffuse beefy red: 3
B) Chemosis
No swelling: 0
Swelling above normal
(includes nicitating membrane): 1
Obvious swelling with partial eversion of the lids: 2
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4
C) Discharge
No discharge: 0
Any amount different from normal
(excluding normal secretion of healthy animals): 1
Discharge with moistening of lids: 2
Discharge with moistening of a wide area
around the eye:


TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Slight to well defined changes were found in the cornea, iris and conjunctiva such as scattered or diffuse opacity, markedly deepened rugae, congestion, swelling and moderate circumcorneal hyperemia of the iris and diffuse crimson color as well as obvious swelling and with partial eversion of eyelids, as far as the conjunctivae were concerned.
Findings were near to equal at 24 and 48 hours, but declined slightly after 72 hours. Changes of the cornea were reversible after 14 days and after 7 day in the other eye structures.

Other effects:

Slight lacrimation

Any other information on results incl. tables

Table: Results of eye irritation

Results of eye irritation study	Cornea	Iris	Conjunctiva
			redness	chemosis
score (range from 0 to maximum score)	0 to 4	0 to 2	0 to 3	0 to 4
60 min	0	0	1	1
24 h	1	1	2	2
48 h	1.3	0.7	2	1.7
72 h	1.3	0.3	1.6	1.3
Day 7	0.3*	0	0	0
Day 14	0.3*	0	0	0
Day 21	0	0	0	0
Average 24h, 48h, 72h	1.2 (1.4*)	0.8	1.9	1.7
Cornea, area effected         1 h                                              24 h                                              48 h                                              72 h                                               Day 7                                               Day 14                                               Day 21	0 3.6 3.3 2.6  0.3* 0 0	0 0 0	0 0 0	0 0 0
Maximum average score	1.3	0.7	2	1.7
Reversibility	c	c	c	c
average time for reversion	14 days	7 days	7 days	7 days
Give method of calculation maximum average score. c :          completely reversible  n c :     not completely reversible  n :        not reversible *:           scoring after fluorescein instillation

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

The Test Substance is classified to be Irritating to eyes under the conditions of the test.

Executive summary:

The local eye irritating potential of TPI 1618 was investigated according to OECD 405 (2002) which equals Commission Directive 2004/73/EC B.5. TPI 1618 was found to be irritating to the eyes of rabbits. Maximal revovry period was 14 days.