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Description of key information

In GLP studies conducted according to OECD Guideline 404 and EU Method B.4, no evidence of irritation was observed when trisodium EDDS was applied for 4 h (under semi-occlusive conditions) to the intact skin of three rabbits (Arcelin, 1993a; Liggett, 1989a) or following repeated exposure of the diluted material to the skin of the upper arm of a number of healthy volunteers (Pitts, 1993; Rybicki, 1993). EDDS acid is a relatively weak acid and would not be classified as corrosive to the eyes or skin on the basis of pH alone. In addition, in a guideline study, EDDS acid caused only moderate transient effects on the conjunctivae of rabbits, which would tend to support a conclusion that significant skin irritation is unlikely. In further support of this, the structurally-related acid EDTA caused, at worst, mild irritation to the skin of one rabbit following a 20-hr exposure to a 50% aqueous preparation (BASF, 1973) and EU experts have concluded “that these findings do not warrant a classification and labelling for skin irritation” (EU, 2004a). Overall, the weight-of-evidence suggests that EDDS acid is likely to be, at most, only a slight skin irritant.
In a GLP study conducted according to OECD Guideline 405, EDDS acid (when applied to the right eye of three rabbits) produced moderate irritation of the conjunctivae after 1 h, which had completely reversed by 48 h. No effects on the cornea or iris were evident (Brunt, 2002b). In addition, instillation of trisodium EDDS at 0.1 g (Arcelin, 1993b) or 4 mg (Liggett, 1989b) to the eyes of three rabbits failed to produce any iridial or corneal effects and only mild transient conjunctivial effects .
There are no data in relation to respiratory irritation in humans or animals. However, the low skin and eye irritation potential of EDDS acid and its trisodium salt suggests that this substance is unlikely to cause such an effect. Indeed, respiratory exposure is expected to be low due to its low vapour pressure.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

In a GLP study conducted according to OECD Guideline 404 and EU Method B.4, the ability of trisodium EDDS to induce skin irritation was assessed in a study in New Zealand White rabbits. The test substance, moistened slightly with water, was applied to the intact skin of the dorsal trunk region of three young rabbits (one male and two females) under a semi-occlusive dressing. The patch was removed after 4 h and the skin washed with lukewarm water and examined for erythema, eschar and edema after 1, 24, 48 and 72 h. No signs of irritation (or corrosion or staining) were evident in any animal throughout the observation period (Arcelin, 1993a).

In a GLP study conducted according to a protocol equivalent to OECD Guideline 404, the ability of trisodium EDDS to cause skin irritation was assessed in a study in New Zealand White rabbits. About 24 h after removal of the hair from the dorso-lumbar region, three rabbits were exposed to 0.66 g of the test substance moistened with water under a semi-occlusive dressing for 4 h. Any remaining test substance was then wiped off with wet tissues and the treated area examined 30 min after removal of the patch and 24, 48 and 72 h later for erythema, eschar formation and edema. None of the animals showed any signs of skin irritation during the observation period (Liggett, 1989a).

Trisodium EDDS was assessed for its ability to induce skin irritation in a 24-h repeat application patch test in twelve healthy volunteers. After swabbing the skin of the upper arm with alcohol to remove any surface oils, 0.4 mL each of 2.94, 14.7 and 29.41% aqueous solutions of test substance were applied in Hill Top chambers to separate sites on the skin of the upper arm. After 24 h the patches were removed and the test sites were washed with water to remove any residue substance. Patches were applied on Friday, Monday and Wednesday, leaving at least 24 h after removal of the previous patch. The test sites were graded, both visually and colorimetrically before each application and 24 h after removal of the third patch. No signs of irritation were evident in any of the volunteers at any time point (Pitts, 1993). In addition, in the induction phase of a sensitisation study, no irritation was seen in humans following 24-h occluded application of trisodium EDDS at a concentration of 5% (in water) to the upper arm of 111 volunteers on alternate days over a 3-week period (9 applications) (Rybicki, 1993).

The use of irritation data on a salt to predict the irritation potential of the equivalent acid is only reliable if large differences in pH are absent. The pH of a 10% w/w aqueous preparation of EDDS acid was determined to be 4.2 (Brunt, 2002b), thus EDDS acid is a relatively weak acid and would not be classified as corrosive to the eyes or skin on the basis of pH alone. In addition, in a guideline study [described below in greater detail], EDDS acid caused only moderate transient effects on the conjunctivae of rabbits, which would tend to support a conclusion that significant skin irritation is unlikely. In further support of this, the closely-structurally-related acid EDTA (no data on purity) was applied to the back of one rabbit as a 50% aqueous preparation for either 1, 5 or 15 minutes or for 20 hours, or on the ear for 20 hours. At 24 hours, mild irritation to the ear was seen. There were no other findings (BASF, 1973). In summarising this early study, EU experts have concluded “that these findings do not warrant a classification and labelling for skin irritation” (EU, 2004a). Overall, the weight-of-evidence suggests that EDDS acid is likely to be, at most, only a slight skin irritant.

In a GLP study conducted according to OECD Guideline 405, EDDS acid was tested for its ability to cause eye irritation in rabbits. The test substance (0.1 mL) was placed in the conjunctival sac of the right eye of three New Zealand White rabbits and the eyelids held together for about one second (no washing). The left eye was left untreated and acted as the control. Assessment of ocular irritation was made at 1, 24, 48 and 72 h using the scoring method of Kay and Calandra (1962) and an ophthalmoscope. No effects on the cornea or iris were evident. Moderate irritation of the conjunctivae was seen with scores of 2 each for redness, chemosis and discharge at 1 h, which had receded to a score of 1 (at the most) for each parameter by 24 h. The eyes of all three rabbits appeared normal at 48 and 72 h. In conclusion, under the conditions of this test, EDDS acid was considered to be non-irritating when applied to the rabbit eye (mean scores at 24, 48 and 72 h) according to the EU CLP and DSD regulations (Brunt, 2002b).

In addition, instillation of trisodium EDDS at 0.1 g (Arcelin, 1993b) or 4 mg (Liggett, 1989b) to the eyes of three rabbits failed to produce any iridial or corneal effects and only mild transient conjunctivial effects.

There are no data in relation to respiratory irritation in humans or animals. However, the low skin and eye irritation potential of EDDS acid suggests that this substance is unlikely to cause such an effect. Indeed, respiratory exposure is expected to be low due to its low vapour pressure.

[Data on trisodium EDDS and EDTA is considered relevant to use for understanding the potential irritancy of EDDS acid, and is acceptable for using as read-across information.]

References (not included elsewhere in IUCLID dossier - need to move to reference list in CSR)

BASF (1973). Abt. Toxikologie, Unpublished test reports (ZST Nr. XXIII/2), 05.06.1973 (cited in EU, 2004a).

Justification for classification or non-classification

According to EU CLP and DSD regulations, EDDS acid would not be classified as a skin, eye or respiratory tract irritant based on the information described.