Sodium [[α,α'-(ethylenediimino)bis[2-hydroxybenzene-1-acetato]](4-)]ferrate(1-)

Endpoint summary

Description of key information

The LD50 values derived from the acute oral toxicity studies with the source substance Fe(Na)EDDHA were > 2000 mg/kg bw. The dermal LD50 of > 2000 mg/kg bw was established, too.

The inhalation (4h) LC50 is > 4200 mg/m³ air (maximum attainable concentration) was established for Fe(Na)EDDHA in a limit test. Based on these results, the target substance o-o-EDDHA (EC 240 -505 -9) is considered to be not acutely toxic by all routes of exposure and does not need to be classified and labelled according to CLP.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-09-13 to 1993-10-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Aimal Production, 4332 Stein/ Switzerland
- Age at study initiation: Young adult
- Weight at study initiation: 184 to 226 g
- Fasting period before study: prior to dosing, the animals were fasted overnight
- Housing: The animal were housed in Macrolon cages type 4, with standardized soft wood bedding; the animals, segregated by sex, were group-housed (5 animals per cage)
- Diet (e.g. ad libitum): Rat diet (NAFAG 890 Tox, NAFAG, Gossau /SG, Switzerland, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 degree C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg

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
- Mortality: daily; a.m. and p.m on working days, a.m. on weekend days
- Signs and symptoms: daily for 14 days
- immediately before administration and on days 7 and 14

- Necropsy of survivors performed: yes

Statistics:

Not performed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occured in this study.

Clinical signs:

other: Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Additionally, diarrhea was observed in all animals. The animals recovered within 5 to 6 days.

Gross pathology:

At necropsy no deviations from normal morphology were found in all animals.

Other findings:

No other findings were noted

No other information

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median LD50 of the test substance FeNaEDDHA in albino rats was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The acute oral toxicity of FeNaEDDHA in albino rats was determined acoording to the OECD Guideline 401 (Acute Oral Toxicity) and the EU Method B.1 (Acute Toxicity Oral). Upon an acute oral administration and a 14 day post-treatment observation period, the LD50 of the test material in albino rats was found to be greater than 2000 mg/kg bw. No mortalities occurred in this study. At necropsy no deviations from normal morphology were found in all animals. Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Additionally, diarrhea was observed in all animals. The animals recovered within 5 to 6 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

There is no deficiencies in the available data set. The data on structurally related substance Fe(Na)EDDHA (CAS 84539-55-9) is reliable and consisitent.

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:

1994-01-20 to 1994-02-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Aimal Production, 4332 Stein/ Switzerland
- Age at study initiation: Young adult
- Weight at study initiation: 191 to 231 g
- Fasting period before study: prior to dosing, the animals were fasted overnight
- Housing: The animal were housed in Macrolon cages type 4, with standardized soft wood bedding; the animals, segregated by sex, were group-housed (5 animals per cage)
- Diet (e.g. ad libitum): Rat diet (NAFAG 890 Tox, NAFAG, Gossau /SG, Switzerland), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degree C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose only exposure system developed by Battelle Reasarch Centre (Geneva/Switzerland) and built from stainless steel by Ciba-Geigy Engineering Dept.
- Exposure chamber volume: internal active volume less than one liter
- Method of holding animals in test chamber: The rats were placed in Macrolon animal holders (Battelle Research Centres, Geneva/Switzerland) positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol.
- Source and rate of air: The low in any individual aerosol delivery tube was standardized to 2 L/min (velocity 1.25 m/s)
- System of generating particulates/aerosols: the aerosol was generated from the solid test material by means of a brush-feed micronising jet mill. The aerosol generation system consists of a dual flexible-brush dust-feed mechanism, modified from a design by Milliman, and jet mill, redesigned from a commercial Trost Jet Mill, to be aerodynamically compatible with the brush feed and the exposure system.
- Method of particle size determination: Particle size analysis was conducted using an eight-stage cascade impactor, equiped with collection substrates punched from regenerated cellulose filters by Schleicher u. Schuell AG. Samples of 1 liter were passed through the impactor. The amount of particles in the eight size classes was determined gravimetrically.
- Treatment of exhaust air: In order to avoid rebreathing of the exhaled air, "fresh" test substance (in first-pass chamber air) was supplied to each animal via individual delivery and exhaust tubes. In addition to the necessary animal and sampling ports, identical "void" outlets were opened in proportion to the total air flow through the chamber. The exhaust air was decontaminated by subsequent passage through a Pall HDC absolute filter.


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The continuity of the particle size distribution was verified by repeated analysis of the aerosol using an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution system to avoid coincidence counts. The number distribution in 48 classes was converted to a mass distribution, based on the bulk density of the test substance, which was determined separately.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The continuity of the particle size distribution was verified by repeated analysis of the aerosol using an APS-33 Aerodynamic Particle Sizer, equipped with appropriate dilution systems to avoid coincidence counts.

Duration of exposure:

4 h

Concentrations:

4202 +/- 188 mg/m³ air

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:
- clicnical symptoms and mortalities: during and after the exposure, as well as daily thereafter for 14 days
- body weight: immediately prior to exposure and on days 7 and 14 of the observation period
- Necropsy of survivors performed: yes

Statistics:

Not performed

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 200 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occured upon exposure to the test item at a concentration of 4202 +/- 188 mg/m³.

Clinical signs:

other: The animals of both sexes exposed to the test article experienced the symptoms piloerection and dyspnea to a similar extent. They recovered within 5 days.

Body weight:

The weight development of all animals was within normal limits.

Gross pathology:

No deviations from normal morphology could be detected in all animals.

No other information

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LC50 of FeNaEDDHA in albino rats was found to be greater than 4200 mg/m³ air.

Executive summary:

The acute inhalation toxicity of FeNaEDDHA in albino rats was determined according to the OECD Guideline 403 (Acute Inhalation Toxicity). Upon a four-hour acute inhalation exposure and a 14-days post-treatment observation period, no mortalities were elicited by the test item at a concentration of 4202 +/- 188 mg/m³. Due to the properties of the test material, it was not possible to generate higher test article concentrations by means of standard aerosol generation equipment. The exposure to the maximum attainable concentration was thus considered a limit test as stated in the OECD test guideline 403. From the absence of mortalities it can be assumed that the LC50 to both sexes is greater than 4200 mg/m³ air.

The animals of both sexes exposed to the test article experienced the symptoms piloerection and dyspnea to a similar extent. They recovered within 5 days. The body weight development was within normal limits. At autopsy, no deviations from normal morphology could be detected in all animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 200 mg/m³ air

Quality of whole database:

An inhalation study conducted with the structural analogue Fe(Na)EDDHA (CAS 84539-55-9) is considered a limit test since the maximum attainable concentration of 4200 mg/m³ was achieved. No further inhalation studies are available. Inhalation is not relevant route of exposure.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hour

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities

Other findings:

Signs of skin irritation: slight to well defined erythema, very slight to slight oedema

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The acute dermal LD50 was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The toxic effects of FeNaEDDHA in Sprague Dawley rats were investigated according to the OECD Guideline 402 on Acute Dermal Toxicity. The animals were dosed dermally in a limit test with a single concentration of test material at a dose level of 2000 mg/kg body weight. The test material was applied to skin of test animals and left for 24 hours in semiocclusive contact.

All animals survived the 2000 mg/kg bw dermal application. No signs of systemic toxicity were noted in treated animals. Signs of skin irritation: slight to well defined erythema and very slight to slight oedema were observed. All animals showed expected bodyweight gain during the study. At necropsy, no deviations from normal morphology were found. The LD50 is greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

There is no deficiencies in the available data set. The data on structurally related substance Fe(Na)EDDHA (CAS 84539-55-9) is reliable and consisitent.

Additional information

Oral route

In two acute oral toxicity studies according to OECD Guideline 401 and GLP, conducted with the structural analogue Fe(Na)EDDHA (CAS 84539 -55 -9) the LD50 in albino rats and Sprague-Dawley CD strain rats was determined to be greater than 2000 mg/kg bw. No deaths and clinical signs were observed in both studies. Body weight development was not impaired. There were no abnormalities at necropsy (Hempstock, 1996, Report No. 003/081; CIBA-GEIGY, 1993b, Report No. 931140) .

Inhalation route

An acute inhalation toxicity study, according to OECD Guideline 403 in albino rats exists for the structurally related Fe(Na)EDDHA (CAS 84539 -55 -9) (CIBA-GEIGY, 1993a, Report No. 931142). Upon a four-hour acute inhalation exposure and a 14-days post-treatment observation period, no mortalities were elicited by the test item at a maximum attainable concentration of 4202 ± 188 mg/m³. Due to the properties of the test material, it was not possible to generate higher test article concentrations by means of standard aerosol generation equipment. The exposure to the maximum attainable concentration was thus considered a limit test as stated in the OECD test guideline 403. From the absence of mortalities it can be assumed that the LC50 to both sexes is greater than 4200 mg/m³ air. The animals of both sexes exposed to the test article experienced the symptoms piloerection and dyspnoea to a similar extent. They recovered within 5 days. At autopsy, no deviations from normal morphology could be detected in all animals.

Dermal route

Two acute dermal toxicity studies (limit test), according to OECD Guideline 402 were performed with the structural analogue test substance Fe(Na)EDDHA (CAS 84539 -55 -9) in Sprague-Dawley CD strain rats and in albino rats (Hempstock, 1996, Report No. 003/082; CIBA-GEIGY, 1993b, Report No. 931141). All animals survived the 2000 mg/kg bw dermal application. No mortalities occurred in both studies and body weight development was not impaired. No clinical signs of toxicity were observed. The acute dermal LD50 values were considered to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

The source substance Fe(Na)EDDHA did not produced clinical signs and deaths in animals treated with 2000 mg/kg bw in the oral acute toxicity studies. The LD50 (rat) was greater than 2000 mg/kg bw. Therefore, the substance doe not meet the criteria for classification and labelling for oral toxicity in accordance with European Regulation (EC) No. 1272/2008.

The source substance Fe(Na)EDDHA did not produce mortalities and findings at necropsy in the acute inhalation toxicity study. The LC50 was greater than 4.2 mg/L. Therefore, the substance does not meet the criteria for classification and labelling for inhalation toxicity in accordance with European Regulation (EC) No. 1272/2008.

The source substance Fe(Na)EDDHA did not produced mortality, clinical signs, affected body weights or findings at necropsy in the acute dermal toxicity studies. LD50 was greater than 2000 mg/kg bw. No dermal irritation was observed. Therefore the substance does not meet the criteria for classification and labelling for dermal toxicity in accordance with European Regulation (EC) No. 1272/2008.