N-(2-hydroxyethyl)ethylenediaminetriacetic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18 May 1982 - 8 June 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, documentation is sufficient for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Principles of method if other than guideline:

This study followed internal Dow procedures

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 2-(carboxylatomethyl(2-hydroxyethyl)amino)ethyliminodi(acetate)

EC Number:

205-381-9

EC Name:

Trisodium 2-(carboxylatomethyl(2-hydroxyethyl)amino)ethyliminodi(acetate)

Cas Number:

139-89-9

Molecular formula:

C10H18N2O7.3Na

IUPAC Name:

trisodium [{2-[bis(carboxylatomethyl)amino]ethyl}(2-hydroxyethyl)amino]acetate

Details on test material:

- Name of test material (as cited in study report): VERSENOL * 120 + 1.9% EXCESS SODIUM HYDROXIDE, also known as hydroxyethyl ethylene diamine triacetate, trisodium salt
- Physical state: liquid
- Source: Larkin Laboratory, Midland, Michigan, USA
- Other: pale yellow color

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Langshaw Farms, Augusta, Michigan, USA
- Other: Female
- All other template details: Not reported

ENVIRONMENTAL CONDITIONS - Not reported

IN-LIFE DATES: Not reported

Test system

Vehicle:

other: VERSENOL * 120 + 1.9% EXCESS SODIUM HYDROXIDE

Controls:

no

Amount / concentration applied:

~0.1 mL or 0.1 g

Duration of treatment / exposure:

Washed and unwashed - Test material of ~ 0.1 mL or 0.1 g was placed in the conjunctival sac of the eyes.

Washed - Following a 30 seconds exposure period the right eye was washed for 2 minutes with tepid, flowing water.

Unwashed. The test material was instilled in the left eye which was left unwashed.

Observation period (in vivo):

At various time intervals both eyes were examined for conjunctival irritation, corneal injury and irritation to the iris. The behavior of the animal was observed for indication of pain or discomfort. A drop of 5% fluorescein was used to help assess corneal injury at 1-hour reading and all subsequent readings.
immediate
after 1hour
after 24 hours
after 48 hours
after 7 days
after 14 days
after 21 days

Number of animals or in vitro replicates:

One

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with tepid flowing tap water to right eye for 2 minutes
- Time after start of exposure: 30 seconds

SCORING SYSTEM: see table in results

TOOL USED TO ASSESS SCORE: 5% aqueous fluorescein

Results and discussion

In vivo

Results

Irritation parameter:

other: combination of conjunctiva, cornea, iris

Basis:

animal #1

Time point:

other: 21 days

Score:

>= 1 - <= 6

Max. score:

6

Reversibility:

fully reversible within: 14 days if washed out after 30 seconds

Remarks on result:

other: see Table 1

Irritant / corrosive response data:

See Table 1

Other effects:

Not reported

Any other information on results incl. tables

Table 1. Eye irritation test results.

immediate

response       not washed (left)       washed (right)

pain                     *                                  6 

conjunctiva             3                                3

cornea                    2                                2

iris                          4                                4

* - anesthetized eye

1 hour

response                      not washed (left)      washed (right)

conjunctiva                            4                             4

cornea (before stain)              4                            3

cornea (after stain)                 4                             4 

iris                                          3                            5

24 hour

response                      not washed (left)      washed (right)

conjunctiva                            4                            4

cornea (before stain)              4                            3

cornea (after stain)                 4                            4    

iris                                        4                            4

48 hour

response                      not washed (left)      washed (right)

conjunctiva                            4                            4

cornea (before stain)              4                            2

cornea (after stain)                 4                            4

iris                                         4                            4        

7 days

response                      not washed (left)      washed (right)

conjunctiva                            2                            2

cornea (before stain)              6  *                          1

cornea (after stain)                 3                            1

iris                                         4                            3 

* Cornea 95% opaque, vascularization on top area of cornea. Right cornea appears to be ulcerated.

14 days

response                      not washed (left)      washed (right)

conjunctiva                            2                            2

cornea (before stain)              6   *                         1       

cornea (after stain)                 2                            1

iris                                          @                           1

* - Cornea has vascularization

@ - Iris cannot be evaluated

21 days

response                      not washed (left)      washed (right)

conjunctiva                            2                            1

cornea (before stain)              5   *                         1

cornea (after stain)                  2                            1

iris                                          1                            1

* - cornea has vasularization and the area of opacity is < 50% of cornea

KEY

Pain

1 - No response.

2 - Very slight. No more than a few blinks - Normal in a minute or so.

3 - Slight. Blinks - tries to open but can't. Reflexes close eye.

4 - Moderate. Holds eye shut and puts pressure on lids, may rub eye with paw.

5 - Severe. Holds eye shut vigorously, rubs eye with paw - may squeal.

6 - Very severe. Holds eye shut vigorously. May squeal, claws at eye, jumps, tries to escape.

Conjunctival response

1 - None.

2 - Very slight. Capillaries prominent. Very slight swelling and/or redness.

3 - Slight. Conjunctival membranes somewhat inflamed. May be sclero-corneal inflammation. Similar to response from a mild soap.

4 - Moderate. Conjunctival membranes inflamed and sore, lids swollen and reddened.

5 - Severe. Conjunctival membranes red and swollen. Nictitating membrane sore and inflamed.

6 - Very Severe. Conjunctival membranes markedly reddened and swollen. Nictitating membrane edematous. Exudate contains pus - eye may be suck shut.

Corneal Response (before Staining)

1 - No response

2 - Very slight haziness.

3 - Slight. Cloudy in parts.

4 - Moderate. Cloudy over whole but not opaque.

5 - Severe. Cornea up to 50% opaque.

6 - Very severe. Cornea completely opaque.

Corneal Response (after staining)

1 - None.

2 - Very slight haziness. Few areas of epithelial injury. Probably heal in 24 - 48 hours.

3 - Slight. Up to 50% of eye covered with shallow epithelial injury. Probably heals.

4 - Moderate. 50 - 100% of eye injured but lesions are shallow. Doubtful if vision will be impaired.

5 - Severe. Marked injury over whole area which may result in loss of eye.

6 - Very severe. Eye lost.

Irritation of the iris

1 - No response.

2 - Very Slight.

3 - Slight. Just perceptible.

4 - Moderate. Definitely perceptible

5 - Severe. Marked change.

6 - Very severe. Complete loss of function.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Installation of Versenol 120 + 1.9% excess sodium hydroxide into the unwashed eye of a female New Zealand white rabbit resulted in moderate conjunctival redness and swelling, moderate reddening of the iris and corneal opacity. Signs of irritation were still exhibited 21 days following exposure. When sample was washed after exposure for 30 seconds, signs of irritation persisted until 14 days post-exposure.

Executive summary:

A sample of Versenol 120 + 1.9% excess sodium hydroxide also known as hydroxyethyl ethylene diamine triacetate, trisodium salt was submitted for assessment of eye irritation potential. The eye irritation test was conducted on a female New Zealand white rabbit.

Instillation of this undiluted material into the rabbit eye which was subsequently washed resulted in marked discomfort, moderate conjunctival redness and swelling, marked reddening of the iris and moderate corneal cloudiness. All signs of irritation were essentially absent 14 days post-exposure.

Instillation of this undiluted material into the unwashed eye of the rabbit resulted in moderate conjunctival reddened and swelling, moderate reddening of the iris and corneal opacity. Signs of irritation were still exhibited 21 days following exposure. Chemical workers' goggles are recommended whenever the likelihood of human eye contact exists, as permanent impairment of vision may result. If contact does occur, contaminated eyes must be flushed immediately with copious amounts of water. Medical attention should be obtained.