Trisodium dihydrogen -N,N-[bis[2-[bis(carboxylatomethyl)amino]ethyl]]glycinate

Endpoint summary

Description of key information

Using a read-across extrapolation approach from OECD 404 and 405 guideline studies on the structural analogue DTPA pentasodium salt, DTPA trisodium salt is predicted to be of very mild skin irritancy and slight ocular irritancy. The read-across is supported by the close structural similarity of the two substances and the neutral, as opposed to alkaline, pH of DTPA trisodium salt.

 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

ca. 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No data on batch number and composition; basic data given, comparable to guidelines/standards (max reliability score can be 2)

Justification for type of information:

The source substance (DTPA 5Na) and the target substance (DTPA 3Na) are the pentasodium and trisodium salts of the same organic acid and are therefore structurally very similar. The purity/impurity profile for the source material is not characterised (40% solution as supplied) in the acute dermal irritancy robust study summary, but since the target material is > 99.9% pure and contains no detectable impurities, the extrapolation of acute irritant properties from the source material to the target material is considered valid, particularly in view of the very conservative extrapolation resulting from the significant difference in pH between the two substances (12.52 for DTPA 5Na and 7.5 for DTPA 3Na). The source material acute dermal irritation study was conducted according to OECD test guideline 404 and is considered reliable with restrictions (Category 2).

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Lack of detail on test material (batch number and composition) and age/source of animals. Number of air changes also not mentioned

Principles of method if other than guideline:

Method used described in 'Appraisal of the safety of chemicals in foods, drugs and cosmetics', by the staff of the division of
pharmacology, food and drug administration. Primary irritation score by J.H. Draize (1959).
Test substance was also tested on abraded skin.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not indicated
- Age at study initiation: not indicated
- Weight at study initiation: 2.4-2.6 kg
- Housing: individually
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: not indicated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 45-55
- Air changes (per hr): not indicated.
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: not indicated.

Type of coverage:

occlusive

Preparation of test site:

other: shaved and one side also abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 h

Observation period:

up to 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: on the back
- % coverage: two squares of 2.5 cm
- Type of wrap if used: patches consisted of double layer light gauze; the trunks was wrapped in a rubber sleeve and the animals were immobilized in restrainers


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not indicated
- Time after start of exposure: 4 hours


SCORING SYSTEM: according to Draize (1959). Readings were made immediately after removal of the patches, and 24 and 72
hours thereafter. The cumulative scores 4/24 hours and 72 hours (erythema and oedema) were averaged for bot abraded and
intact skin and added together to calculate the primary irritation index.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 4/24 hours and 72 hours

Score:

0

Reversibility:

other: no irritation at all

Remarks on result:

other: all 3 animals had score: 0

Irritant / corrosive response data:

No irritation

Other effects:

Not indicated

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is not a skin irritant

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used was essentially according to the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irri tation/Corrosion" A single 4 -hour, occluded application of the test material to intact and abraded skin of three rabbits produced no erythema or oedema. All treated skin sites appeared normal at the 4/24 -hour and 72 -hour observation. The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to OECD-GHS labeling regulations. No symbol and risk phrase are required.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

The source substance (DTPA 5Na) and the target substance (DTPA 3Na) are the penta-sodium and tri-sodium salts of the same organic acid and are therefore structurally very similar. They are of comparable high water solubility and DTPA pentasodium salt is alkaline and DTPA trisodium salt neutral pH in aqueous solution (12.52 for DTPA 5Na and 7.5 for DTPA 3Na). Extrapolation of irritancy potential from the source substance to the target substance is therefore considered valid as a 'worst case' scenario.

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

> 99% purity

Species:

rabbit

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Conclusions:

DTPA trisodium salt is predicted to be non-irritant to skin.

Executive summary:

Using a read-across approach from an OECD 404 guideline study on the structural analogue DTPA pentasodium salt, DTPA trisodium salt is predicted to be of very mild skin irritancy. The read-across is supported by the close structural similarity of the two substances and the neutral, as opposed to alkaline, pH of DTPA trisodium salt.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: acceptable, well-documented publication which meets basic scientific principles

Justification for type of information:

The source substance (DTPA 5Na) and the target substance (DTPA 3Na) are the pentasodium and trisodium salts of the same organic acid and are therefore structurally very similar. The purity/impurity profile for the source material is not characterised (40% solution as supplied) in the acute eye irritancy robust study summary, but since the target material is > 99.9% pure and contains no detectable impurities, the extrapolation of acute irritant properties from the source material to the target material is considered valid, particularly in view of the very conservative extrapolation resulting from the significant difference in pH between the two substances (12.52 for DTPA 5Na and 7.5 for DTPA 3Na). The source material eye irritation study was conducted according to OECD test guideline 405 and is considered reliable with restrictions (Category 2).

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Housing: single housing per stainless steel cage (area about 40 x 51 cm)
- Diet (e.g. ad libitum): Ovator Solikanin, Duesseldorf, Germany
- Water (e.g. ad libitum): tap wter (about 250 ml per animal)
- Acclimation period: 8 days before starting the experiment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3

Details on study design:

The acclimatization period was 8 days before starting the study; same housing conditions as during the testing period. Application site: conjunctival sac of the right eye. Observations were made 1 h, 24 h, 48 h, 72 h and 8 days after application. The test substance was not rinsed out.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 h

Score:

6

Max. score:

8

Reversibility:

fully reversible within: 8 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48 h

Score:

4

Max. score:

6

Reversibility:

fully reversible within: 8 days

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

3

Max. score:

5

Reversibility:

fully reversible within: 8 days

Observations after	Animal No.	Cornea		Iris	Conjunctiva				Single irritation score
		Cloudiness	Area		Reddening	Swelling	Secretion
24 hours	1	0	0	0	1	0	0		2
	2	0	0	0	2	1	1		8
	3	0	0	0	2	1	1		8
								Mean	6
48 hours	1	0	0	0	1	0	0		2
	2	0	0	0	2	0	1		6
	3	0	0	0	1	0	1		4
								Mean	4
72 hours	1	0	0	0	1	0	0		2
	2	0	0	0	2	0	1		6
	3	0	0	0	1	0	0		2
								Mean	3
8 days	1	0	0	0	0	0	0		0
	2	0	0	0	0	0	0		0
	3	0	0	0	0	0	0		0
								Mean	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

The source substance (DTPA 5Na) and the target substance (DTPA 3Na) are the penta-sodium and tri-sodium salts of the same organic acid and are therefore structurally very similar. They are of comparable high water solubility and DTPA trisodium salt is neutral and DTPA pentasodium salt alkaline in aqueous solution (7.5 for DTPA 3Na and 12.52 for DTPA 5Na). Extrapolation of irritancy potential from the source material to the target substance is therefore considered valid as a 'worst case' scenario,

Reason / purpose for cross-reference:

read-across: supporting information

Specific details on test material used for the study:

> 99% purity

Species:

rabbit

Vehicle:

unchanged (no vehicle)

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

1

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

0

Conclusions:

DTPA trisodium salt is predicted to be slightly irritant to eyes. .

Executive summary:

Using a read-across extrapolation approach from an OECD 405 guideline study on the structural analogue DTPA pentasodium salt, DTPA trisodium salt is predicted to be slightly irritant to eyes. The read-across is supported by the close structural similarity of the two substances and the neutral, as opposed to alkaline, pH of DTPA trisodium salt.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute dermal irritancy of DTPA pentasodium salt is very mild, with no erythematous or oedematous reactions elicited in abraded or non-abraded rabbit skin (OECD 404). DTPA penta and trisodium salts are structurally similar, and DTPA pentasodium salt is alkaline and DTPA trisodium salt neutral in aqueous solution. Based on a read-across approach, DTPA trisodium salt is therefore predicted to be very mildly irritant to skin. 

 

DTPA pentasodium salt elicits slight eye irritation, with transient conjunctival erythema and oedema in rabbits (OECD 405). DTPA pentasodium salt is structurally similar to DTPA trisodium salt, but has an alkaline pH in aqueous solution, whereas DTPA trisodium salt is neutral. Based on a 'worst case' read-across approach, DTPA trisodium salt is predicted to be of slight ocular irritancy.

Justification for classification or non-classification

DTPA trisodium salt is considered not to meet the CLP criteria for classification for acute skin or eye irritation.