L-Aspartic acid, N,N'-1,2-ethanediylbis-, sodium salt (1:3)

Endpoint summary

Description of key information

No acute toxicity data in humans are available.

In GLP studies conducted according to OECD Guideline 401 (available at the time), acute oral LD50 values of >2 g/kg bw (Mahl, 1993a) and >2.7 g/kg bw (Kynoch et al. 1989) have been determined for trisodium EDDS in male and female rats following gavage administration.

In a GLP study conducted according to OECD Guideline 403 (available at the time), an acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3; the highest attainable concentration) in air was determined for trisodium EDDS in male and female rats following whole body exposure (Hardy and Jackson, 1989).

In GLP studies conducted according to OECD Guideline 402 (available at the time), acute dermal 24-h LD50 values of >2 g/kg bw (Mahl, 1993b) and >2.64 g/kg bw (Liggett and Allan, 1989) have been determined for trisodium EDDS in male and female rabbits and rats, respectively, following semi-occlusive application.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 April to 12 May 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd, Wölferstrasse 4, CH-4414 F¿llinsdorf, Switzerland
- Age at study initiation: males, 8 weeks; females, 10 weeks
- Weight at study initiation: males, 195.5-203.0 g; females, 169.7-181.7 g
- Fasting period before study: 16.5 h
- Housing: Makrolon type-3 cages on softwood bedding
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle:included in list of recommended vehicles
- Purity: double-distilled

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): homogenised in vehicle, kept in suspension during dosing using a magnetic stirrer

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed four times on day of dosing (last check, 5 h after treatment), then daily. Weighed pre-dosing, then weekly
- Necropsy of survivors performed: yes

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No signs of toxicity were observed.

Gross pathology:

No treatment-related organ abnormalities were observed on macroscopic examination

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 401 (available at the time), an acute oral LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats following gavage administration.

Executive summary:

In a GLP study conducted according to OECD Guideline 401 (available at the time), trisodium EDDS was studied for acute toxicity after single oral administration to five rats of each sex. The test substance was given by gavage as an aqueous suspension at a dose of 2000 mg/kg bw.

None of the animals died or showed signs of toxicity during the 14-day observation period, and the body weight of the animals was not adversely affected. At necropsy, no abnormalities were evident in the rats upon macroscopic examination.

An acute oral LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats. According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the oral route under the conditions of this test.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

3 to 17 May 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

CD-1

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2700 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 700 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No clinical signs of toxicity were observed during the 14-day observation period, apart from pilo-erection in all rats for the first few hours after dosing.

Gross pathology:

Enlarged cervical lymph nodes were observed in all males and two females at necropsy. Cortical depression was detected in the left kidney of one male; mild or moderate hydronephrotic kidneys were seen in a further two males. No other macroscopic abnormalites were observed.

Other findings:

Microscopic examination detected moderate bilateral basophilic cortical tubules, moderate dilated cortical tubules with some eosinophilic material, and minimal bilateral eosinophilic material in the Bowman's space of some tubules in one male. These changes were considered to be substance related.

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 401 (available at the time), an acute oral LD50 value of >2700 mg/kg bw was determined for trisodium EDDS in male and female rats following gavage administration.

Executive summary:

In a GLP study conducted according to OECD Guideline 401 (available at the time), trisodium EDDS was assessed for acute toxicity after single oral administration in five rats of each sex. The test substance was given by gavage as an aqueous solution at a dose of 2700 mg/kg bw.

No animal died during the study and no clinical signs of toxicity were observed during the 14-day observation period, apart from pilo-erection in all animals for the first few hours after dosing. At necropsy, enlarged cervical lymph nodes were observed in all five males and two females. Cortical depression was detected in the left kidney of one male; mild or moderate hydronephrotic kidneys were seen in a further two males. Microscopic examination detected moderate bilateral basophilic cortical tubules, moderate dilated cortical tubules with some eosinophilic material and minimal bilateral eosinophilic material in the Bowman's space of some tubules in one male.

An acute oral LD50 value of >2700 mg/kg bw was determined for trisodium EDDS in male and female rats. According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the oral route under the conditions of this test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 April to 12 May 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River USA, Portage, Michigan, USA
- Age at study initiation: males, 7 weeks; females, 9 weeks
- Weight at study initiation: males, 212-229 g; females, 201-218 g
- Fasting period before study: no
- Housing: polypropylene cages with wire mesh tops and floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 35-65 (except on 7 days when low values were recorded)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright dust generator
- Exposure chamber volume: 120 L
- Method of holding animals in test chamber: held in stainless steel mesh cages partitioned to provide 10 individual animal compartments
- Source and rate of air: compressed air, 25 L/min
- Method of conditioning air: no data
- System of generating particulates/aerosols: test substance packed into the Wright dust generator using a hydraulic bench press; even density was achieved by packing the generator in stages and applying a 1.0 ton weight. The test atmosphere was generated by resuspending the test substance scraped from the surface of the compressed powder in a stream of dry air
- Method of particle size determination: air samples taken using an Andersen mini-sampler and the collected material was weighed to detemine the particle size distribution
- Treatment of exhaust air: passed out through small holes in chamber to extraction system
- Temperature, humidity, pressure in air chamber: air temperature measured at 30 min intervals and found to be 23oC; relative humidity was measured using a water vapour analyser every 30 min and found to have a mean of 62.3% (mean 43.1% for the control group)

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 22% was 5.5 um or less in aerodynamic size (respirable size)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 4 h

Concentrations:

1.49 mg/L of air (highest attainable concentration using the methods described)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed continuously during exposure and at least twice daily until study termination. Body weights recorded on day of exposure and days 1, 3, 7 and 14 of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights of lungs, liver and kidneys

Statistics:

Analysis of variance was carried out on the lung, liver and kidney weights. Body weights were compared using Student's "t" distribution

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 490 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: Signs consistent with exposure to an irritant dust (eye squint, salivation and restless behaviour) were observed during treatment, but had disappeared within an hour post-exposure.

Body weight:

Body weights were not significantly different compared to the control groups.

Gross pathology:

No abnormalities were detected on macroscopic examination.

Other findings:

Lung, liver and kidney weights were comparable to the controls.

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 403 (available at the time), an acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3; the highest attainable concentration) in air was determined for trisodium EDDS in male and female rats following whole body exposure.

Executive summary:

In a GLP study conducted according to OECD Guideline 403 (available at the time), the acute inhalation toxicity of trisodium EDDS was assessed in a study on male and female rats.

Groups of five rats of each sex were exposed continuously (by whole body contact) to air containing 0 or 1.49 mg trisodium EDDS/L for 4 h. The animals were then observed for a 14-day period for mortality, clinical signs of toxicity and changes in body weight before being examined macroscopically for gross abnormalities and for differences in the lung, liver and kidney weights compared to the controls.

No deaths occurred during the study and no clinical signs of toxicity were evident. Although eye squint, salivation and restless behaviour was observed in the treated groups (consistent with exposure to an irritant dust) these had disappeared within 1 h post-treatment. The test substance remained on the fur of the exposed groups. Body weights were not significantly different compared to the control groups; at necropsy there were no abnormal findings and the lung, liver and kidney weights were comparable to those of the controls.

An acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3) in air was determined for trisodium EDDS in male and female rats following whole body exposure. According to EU CLP regulation, trisodium EDDS would not be classiffied as acutely toxic by the inhalation route under the conditions of this test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 1 490 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 April to 10 May 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 2.3-2.7 kg (although report states 2.3-2.7 g)
- Fasting period before study: no
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.0
- Humidity (%): mean 52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

used to moisten the test substance and aid adhesion to the skin

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: gauze held in place with a "non-occlusive" dressing encirclating the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30-40oC) and blotted dry
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw
- For solids, paste formed: no (moistened with water after application)

VEHICLE
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw

Duration of exposure:

24 h

Doses:

2640 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at "frequent intervals" on day of dosing, then at least twice daily until study termination. Weighed before dosing, then weekly
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abdominal and thoracic cavities
other: erythema, eschar formation, oedema of the test site scored daily

Statistics:

not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 640 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No deaths occurred during the study

Clinical signs:

other: Diarrhoea was observed in 3 males and 3 females lasting about 2 days for each animal, but this was not considered to be treatment-related

Gross pathology:

No abnormalities were observed following macroscopic examination of the thoracic and abdominal organs and tissues

Other findings:

No irritation reactions were detected

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 402 (available at the time), an acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits following semi-occlusive application.

Executive summary:

In a GLP study conducted according to OECD Guideline 402 (available at the time), the acute dermal toxicity of trisodium EDDS was assessed in male and female New Zealand White rabbits.

The test powder (2.64 g/kg bw) was applied to the clipped backs of five rabbits of each sex, moistened with water to aid adhesion to the skin and covered with a semi-occlusive dressing for 24 h. The test substance was subsequently removed by washing in warm water and blotting dry. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs of the thoracic and abdominal cavities were examined macroscopically.

No clinical signs of toxicity were seen in any of the animals and no deaths occurred during the 14-d observation period. Diarrhoea, lasting about 2 days in three animals of each sex was not considered to be treatment-related. At necropsy, no gross changes in organs or tissues were detected.

An acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits. According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the dermal route under the conditions of this test.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 April to 11 May 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

the bw of three female rats at 196-199 g was very slightly below the recommended wt range (200-300 g)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

yes

Remarks:

the bw of three female rats at 196-199 g was very slightly below the recommended wt range (200-300 g)

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd, Wölferstrasse 4, CH-4414 F¿llinsdorf, Switzerland
- Age at study initiation: males, 10 weeks; females, 12 weeks
- Weight at study initiation: males, 230.4-243.5 g; females, 196.0-205.4 g
- Fasting period before study: no data
- Housing: Makrolon type-3 cages on softwood bedding
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: to clipped skin on back of rats
- % coverage: about 10%
- Type of wrap if used: semi-occlusive dressing, fixed with an elastic adhesive bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm water and dried with paper towels
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 500 mg/mL
- Constant volume or concentration used: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed four times during the day of dosing (last check conducted 5 h after application) and thereafter once daily for 14 days. Body weights were recorded before treatment and then weekly
- Necropsy of survivors performed: yes
- Other examinations performed: irritation at the applicaiton site

Statistics:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

none

Clinical signs:

other: No clinical or local skin signs of toxicity

Gross pathology:

Effects on organs: no treatment-related macroscopic findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP study conducted according to OECD Guideline 402 (available at the time), an acute dermal 24-h LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats following semi-occlusive application.

Executive summary:

In a GLP study conducted according to OECD Guideline 402 (available at the time), trisodium EDDS was studied for acute toxicity after single, semi-occlusive, application to the shaved backs of 5 male and 5 female Wistar rats. The test substance was applied as an aqueous suspension at a dose of 2000 mg/kg bw for 24 h, and was subsequently removed by washing in warm water. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs examined macroscopically.

No deaths were seen, and none of the animals showed signs of toxicity during the 14-day observation period. No treatment-related effects on body weight gain were reported, and no irritation at the site of application was observed. At necropsy, no organ abnormalities were evident in the rats upon macroscopic examination.

 

An acute dermal 24-h LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats following semi-occlusive application. According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the dermal route under the conditions of this test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

No acute toxicity data in humans are available.

In a GLP study conducted according to OECD Guideline 401 (available at the time), trisodium EDDS was studied for acute toxicity after single gavage administration to five rats of each sex at a dose of 2000 mg/kg bw (in water). None of the animals died or showed signs of toxicity during the 14-day observation period, and the body weight of the animals was not adversely affected. At necropsy, no abnormalities were evident in the rats upon macroscopic examination. An acute oral LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats (Mahl, 1993a).

In a GLP study conducted according to OECD Guideline 401 (available at the time), trisodium EDDS was assessed for acute toxicity after single oral administration in five rats of each sex. The test substance was given by gavage as an aqueous solution at a dose of 2700 mg/kg bw. No animal died during the study and no clinical signs of toxicity were observed during the 14-day observation period, apart from pilo-erection in all animals for the first few hours after dosing. At necropsy, enlarged cervical lymph nodes were observed in all five males and two females. Cortical depression was detected in the left kidney of one male; mild or moderate hydronephrotic kidneys were seen in a further two males. Microscopic examination detected moderate bilateral basophilic cortical tubules, moderate dilated cortical tubules with some eosinophilic material and minimal bilateral eosinophilic material in the Bowman's space of some tubules in one male. An acute oral LD50 value of >2700 mg/kg bw was determined for trisodium EDDS in male and female rats (Kynoch et al. 1989).

In a GLP study conducted according to OECD Guideline 403 (available at the time), the acute inhalation toxicity of trisodium EDDS was assessed in a study on male and female rats. Groups of five rats of each sex were exposed continuously (by whole body contact) for 4 h to air containing 0 or 1.49 mg trisodium EDDS/L (about 1490 mg/m3; the highest attainable concentration with the equipment used). The animals were then observed for a 14-day period for mortality, clinical signs of toxicity and changes in body weight before being examined macroscopically for gross abnormalities and for differences in the lung, liver and kidney weights compared to the control groups. No deaths occurred during the study and no clinical signs of toxicity were evident. Although eye squint, salivation and restless behaviour were observed during the treatment period (consistent with exposure to an irritant dust) these had disappeared within 1 h post-treatment. The test substance remained on the fur of the exposed groups. Body weights were not significantly different compared to the control groups; at necropsy there were no abnormal findings and the lung, liver and kidney weights were comparable to those of the controls. An acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3) in air was determined for trisodium EDDS in male and female rats following whole body exposure (Hardy and Jackson, 1989).

In a GLP study conducted according to OECD Guideline 402 (available at the time), the acute dermal toxicity of trisodium EDDS was assessed in male and female New Zealand White rabbits. The test powder (2.64 g/kg bw) was applied to the clipped backs of five rabbits of each sex, moistened with water to aid adhesion to the skin and covered with a semi-occlusive dressing for 24 h. The test substance was subsequently removed by washing in warm water and blotting dry. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs of the thoracic and abdominal cavities were examined macroscopically. No clinical signs of toxicity were seen in any of the animals and no deaths occurred during the 14-d observation period. Diarrhoea, lasting about 2 days in three animals of each sex was not considered to be treatment-related. At necropsy, no gross changes in organs or tissues were detected. An acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits (Liggett and Allan, 1989).

In a GLP study conducted according to OECD Guideline 402 (available at the time), trisodium EDDS was studied for acute toxicity after single, semi-occlusive, application to the shaved backs of 5 male and 5 female Wistar rats. The test substance was applied as an aqueous suspension at a dose of 2000 mg/kg bw for 24 h, and was subsequently removed by washing in warm water. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs examined macroscopically. No deaths were seen, and none of the animals showed signs of toxicity during the 14-day observation period. No treatment-related effects on body weight gain were reported, and no irritation at the site of application was observed. At necropsy, no organ abnormalities were evident in the rats upon macroscopic examination. An acute dermal 24-h LD50 value of >2000 mg/kg bw was determined for trisodium EDDS in male and female rats (Mahl, 1993b).

Justification for classification or non-classification

According to EU CLP regulation, trisodium EDDS would not be classified as acutely toxic by the oral, inhalation or dermal routes under the conditions of the tests described.