Disodium 2-hydroxyethyliminodi(acetate)

Endpoint summary

Description of key information

Based on a mean score of 0.75 for erythema and 0.58 for oedema, and the full disappearance of the effects within 2 days, the test material was not considered to be irritating to the rabbit skin according to OECD-GHS.

Based on two studies with the read across substance NTA-NA3 (see also section 13) and one RF study with EDG-Na2 it was concluded that both substances are irritating to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no info

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited reported study, with several deviations compared to current guidelines. Application was 24 h instead of 4 h; application was occluded instead of semi-occluded; 6 rabbits were used instead of 3. No data on batch number and identity/purity.

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.11

Principles of method if other than guideline:

Deviations from current OECD 404: Occlusive rather than semi-occlusive application was used; 24-h application rather than 4-h; 6
animals were used rather than 3.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dutchland Rabbit Farms, USA
- Age at study initiation: no info
- Weight at study initiation: 1.6-2.1 kg
- Housing: no info
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: no info

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no info
- Humidity (%): no info
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): no info

IN-LIFE DATES: no info

Type of coverage:

occlusive

Preparation of test site:

other: clipped and abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
- Concentration (if solution): undiluted

VEHICLE: not used

Duration of treatment / exposure:

24 h

Observation period:

Immediately after patch removal (at 24 h) and at 72 h (48 h after patch removal).
Animals were kept for a week in total after patch removal.

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: no info
- % coverage: no info
- Type of wrap if used: double layer of surgical gauze overwrapped with pure latex rubber dental dam; this was immobilized using adhesive bandages

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no info
- Time after start of exposure: patch was removed 24 h after start applications

SCORING SYSTEM:
SCORING SYSTEM:

EVALUATION OF SKIN REACTIONS
Erythema and eschar formation
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4

Oedema formation
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by
definite raising) 2
Moderate oedema (raised approximately 1 mm) 3
Severe oedema (raised more than 1 mm and
extending beyond area of exposure) 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 0 and 48 h after patch removal

Score:

0.75

Max. score:

4

Reversibility:

fully reversible within: 2 days after patch removal

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 0 and 48 h after patch removal

Score:

0.58

Max. score:

4

Reversibility:

fully reversible within: 2 days after patch removal

Irritant / corrosive response data:

Slight irritation was observed immediately after patch removal; both on intact and abraded skin, dermal changes had disappeared
within 2 days.

Other effects:

None

Summary of dermal lesions (following 24-h application)

Animal no.	Effect	Hour	Days after start of application					Mean score erythema (0/48 h)	Mean score oedema (0/48 h)
		1	1 (0 h)*	2	3 (48 h)*	7	14
1	Erythema/ eschar Oedema	-	2 1	-	0 0	-	-	1	0.5
2	Erythema/ eschar Oedema	-	1 0	-	0 0	-	-	0.5	0
3	Erythema/ eschar Oedema	-	1 1	-	0 0	-	-	0.5	0.5
4	Erythema/ eschar Oedema	-	2 1	-	0 0	-	-	1	0.5
5	Erythema/ eschar Oedema	-	1 2	-	0 0	-	-	0.5	1
6	Erythema/ eschar Oedema	-	2 2	-	0 0	-	-	1	1
Mean all animals								0.75	0.58

* 0 h and 48 h is after patch removal (or 24 h and 72 h after the start of application)

Interpretation of results:

GHS criteria not met

Conclusions:

Based on a mean score of 0.75 for erythema and 0.58 for oedema, and the full disappearance of the effects within 2 days, the test material was not considered to be irritating to the rabbit skin according to OECD-GHS.

Executive summary:

A study was performed to assess the irritancy potential of the test material, HAMPSHIRE EDG 0500 -01, to the skin of the New Zealand White rabbit. The method used followed the recommendations of the 16 CFR 1500.11. A single 24 -hour, occluded application of the test material to the intact and abraded skin of six rabbits produced very slight erythema and oedema on intact skin. All treated skin sites (including the abraded sites) appeared normal at the 72 -hour observation (48 h after patch removal). The test material produced a mean erythema score of 0.75 and a mean oedema score of 0.58 and was classified as a non-irritant to rabbit skin according to OECD-GHS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, acceptable for assessment; limited information on test substance; observation period only 7 days

Justification for type of information:

See RA document in section 13

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

scoring method according to Draize et al., 1944

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 h

Score:

33.6

Max. score:

37

Remarks on result:

other: considerable discomfort immediately upon application

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

27.6

Max. score:

30

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 h

Score:

20.6

Max. score:

24

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 3d

Score:

14

Max. score:

19

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 5 d

Score:

8.3

Max. score:

11

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 d

Score:

4.6

Max. score:

8

Reversibility:

not fully reversible within: 7 d

Remarks on result:

other: leaving mild redness and slight corneal dullness

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Trisodium nitrilotriacetate (NTA) was classified as a moderate eye irritant in male and female rabbits. The average maximum score was 33.6 out of a possible 110 one hour after application.

Executive summary:

In a primary eye irritation study 100 mg of finely ground Trisodium nitrilotriacetate (NTA) was instilled into the conjunctival sac of right eye of albino rabbits (0-1/sex) for 24 hours. Eyes were rinsed with isotonic saline solution after 24 hours. Animals then were observed for several days. Irritation was scored by the method of Draize et.al., 1944.

Considerable discomfort was shown immediately upon application. Copious discharge, edema with partial eversion of the lids, moderate redness, and sufficient congestion to mildly obsure iris details was recorded after one hour. Discharge reduced in 24 hours as well as edema. Both had disappeared within 5 days, leaving mild redness and slight corneal dullness.

Trisodium nitrilotriacetate (NTA) was classed by expert judgement as a moderate eye irritant in male and female rabbits. The average maximum score was 33.6 out of a possible 110 after one hour.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a skin irritation test in rabbits, EDG-Na2 was only slightly irritating to the skin. These results were comparable to those of NTA-Na3.

Only a RF eye irritation test was available and results were used from studies with the structurally analogue NTA-Na3 (see also read across document in section 13). Ambiguous results were reported for the eye irritating properties of Na3NTA. A lack of irritation up to severe effects were reported. Studies conducted with diluted NTA-Na3 are of limited use for the risk assessment of pure, undiluted compound. One study applied undiluted NTA-Na3 concluding moderate eye irritation after application of 100 mg finely ground powder (Younger, 1968). Also the RF study with EDG-Na2 showed eye irritation.

Justification for selection of skin irritation / corrosion endpoint:

The results of this study were confirmed in a supporting study with EDG-Na2.

Justification for selection of eye irritation endpoint:

Based on two studies with the read across substance NTA-NA3 (see also section 13) and one RF study with EDG-Na2.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Based on the results of a skin irritation test in rabbits, EDG-Na2 does not need classification for skin irritation.

 

Only a RF eye irritation test is available and results were also used from studies with the structurally analogue NTA-Na3. One study using undiluted NTA-Na3 showed moderate eye irritation after application of 100 mg finely ground powder. The RF study with EDG-Na2 also showed eye irritation. This is in accordance with the current classification as irritating to eyes (R36), or GHS Cat. 2 (H319). The same classification is therefore used for EDG-Na2.