isliFe

Endpoint summary

Description of key information

The LD50 value derived from the acute oral toxicity study with MEAHA-Fe is > 2000 mg/kg bw. The dermal LD50 based on read-across from FeNa-EDDHA is > 2000 mg/kg bw.  The inhalation (4h) LC50 based on read-across from FeNa-EDDHA is > 4200 mg/m³ air.

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:

14 May 2019 - 30 May 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Batch No TRODBB06

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Six Sprague Dawley rats (SPF Caw), supplied by Elevage JANVIER LABS (53940 Le Genest St Isle – France), were used after an acclimatization period of at least five days. The animals were nulliparous and non-pregnant.
At the beginning of the study, the animals were 8 weeks old.
They were identified prior to inclusion in the test by means of a numbered ring on the edge of one ear.

Group treated (2000 mg/kg): 3 female rats Rf3782 to Rf3784 (Step 1)
3 female rats Rf3786, Rf3788 to Rf3791 (Step 2)
One animal (Rf3787) presenting signs of incorrect gavage the day of the administration was replaced by the animal Rf3791.

Housing
Healthy female rats were housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust bedding which was changed at least 2 times a week. Each cage was installed in conventional air conditioned animal husbandry.
The temperature and relative humidity of the main test were controlled to remain within target ranges of 19°C to 25°C and 30% to 70%, respectively.
The rate of air exchange was at least ten changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (07.00 to 19.00) and twelve hours darkness.

Food and drink
Drinking water (tap-water from public distribution system) and foodstuff (ENVIGO - 2016) were supplied ad libitum. Food was removed on D-1 and then redistributed 4 hours after the test item administration.
Microbiological and chemical analyses of the water were carried out once every six months by Bureau Veritas – Eurofins (FRANCE).

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

As no information was available regarding a possible systemic toxicity of the test item, the first test dose was 2000 mg/kg body weight.
The animals of the treated group received an effective dose of 2000 mg/kg body weight of the test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe).
Distilled water was chosen as it produced the most suitable formulation at the requested concentration.
In the first step of the study, 2.0013 g of the test item were weighed and distilled water was added to a flask q.s. 10 mL.
In the second step of the study, 2.0008 g of the test item were weighed and distilled water was added to a flask q.s. 10 mL.
Just before the administration, the preparations were stirred using a vortex for 30 seconds to obtain dark red solutions.
Each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

yes

Remarks:

Three animals, received the control item Distilled water, administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Details on study design:

Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item.
On day 14, the animals were eathanized and macroscopic observations were entered on individual autopsy sheets.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

No clinical signs related to the administration of the test item were observed during the study.

Body weight:

The body weight evolution of the animals remained normal during the study.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, the LD50 of the test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) is higher than 2000 mg/kg body weight.
In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

The test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.

Executive summary:

The test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) was administered to a group of 6 female Sprague Dawley rats at the dose of 2000 mg/kg body weight.

The experimental protocol was established according to the official method as defined in the O.E.C.D. Test Guideline No. 423 dated December 17th, 2001.

No mortality occurred during the study.

No clinical signs related to the administration of the test item were observed during the study.

The body weight evolution of the animals remained normal during the study.

The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

In conclusion, the LD50 of the test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) is higher than 2000 mg/kg body weight.

In accordance with the O.E.C.D. Test Guideline No. 423, the LD50 cut-off of the test item may be considered as 5000 mg/kg body weight by oral route in the rat.

The test item Acetic acid, oxo-, sodium salt, reaction products with ethanolamine and phenol, sodium hydroxide and ferric chloride (MEAHA Fe) does not have to be classified in accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The original study is a Klimish 1 guideline study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Key result

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. The 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.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 for acute inhalation toxicity of FeNa-EDDHA in albino rats was found to be greater than 4200 mg/m3 air.

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Executive summary:

The acute inhalation toxicity of FeNa-EDDHA 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. A autopsy, no deviations from normal morphology could be detected in all animals.

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 200 mg/m³

Quality of whole database:

The original study is a Klimish 1 guideline study.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths

Clinical signs:

No signs of systemic toxicity

Body weight:

All animals showed expected gain in bodyweight during the study

Gross pathology:

No abnormalities

Other findings:

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

Interpretation of results:

GHS criteria not met

Conclusions:

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

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Executive summary:

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

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

supporting study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Key result

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:

Piloerection and hunched posture were seen, being common symptoms in acute dermal tests.

Body weight:

- day 14:
- males: 320 ± 12 g
- females: 243 ± 7.7 g

Gross pathology:

At necropsy no deviations from normal morphology were found.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for acute dermal toxicity of FeNa-EDDHA is greater than 2000 mg/kg body weight.

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Executive summary:

The toxic effects of FeNa-EDDHA in the albino rabbit were investiagte according to the OECD Guideline 402 on Acute Dermal Toxicity. Ten healthy albino rabbits were dosed dermally in a limit test with a unique concentration of test material at a dose level of 2000 mg/kg body weight.

Approx. 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper. The test substance was evenly dispersed on the skin. It was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage. After 24 hours the dressing was removed and the skin was cleaned with lukewarm water.

The animals were observed daily for signs of mortality, toxicity and pharmacological effects. Bodyweights were recorded immediately before application and on days 7 and 14. All animals were examined for gross pathology.

All animals survived the 2000 mg/kg bw dermal application. Piloerection and hunched posture were seen in the study, being common symptoms in acute dermal tests. Body weight changes were normal. At necropsy, no deviations from normal morphology were found. The LD50 of FeNa-EEDHA is greater than 2000 mg/kg body weight.

Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The original study is a Klimish 1 guideline study.

Additional information

Oral route

In an acute oral toxicity study with Acetic acid, oxo-, sodium salt, reaction products with 2-aminoethanol and phenol, sodium hydroxide and iron trichloride (MEAHA-Fe) according to OECD Guideline 423, the LD50 in Sprague-Dawley rats was determined to be greater than 2000 mg/kg bw. Body weight development was not impaired. No deaths occurred in both studies.

Inhalation route

An acute inhalation toxicity study, according to OECD Guideline 403 was performed in albino rats for the substance Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and phenol, iron sodium salts (FeNa-EDDHA, CAS 84539-55-9, EC 283-044-5). 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. From the absence of mortalities it can be assumed that the LC50 for FeNa-EDDHA 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. Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Dermal route

Two acute dermal toxicity studies (limit test), according to OECD Guideline 402 were performed with Acetic acid, oxo-, sodium salt, reaction products with ethylenediamine and phenol, iron sodium salts (FeNa-EDDHA, CAS 84539-55-9, EC 283-044-5) in albino rats and Sprague-Dawley CD strain rat.

All animals survived the 2000 mg/kg bw dermal application. No mortalities occurred in both studies and body weight development was not impaired.

The acute dermal LD50 -values of FeNa-EDDHA were considered to be greater than 2000 mg/kg bw. Based on the structural similarity, the similar physico-chemical properties and the similar acute oral toxicity between FeNa-EDDHA and MEAHA-Fe, identical conclusions are drawn for the read-across target MEAHA-Fe.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study with MEAHA-Fe and read-across from acute inhalation and dermal toxicity studies with the structural analogue FeNa-EDDHA, MEAHA-Fe ( Acetic acid, oxo-, sodium salt, reaction products with 2-aminoethanol and phenol, sodium hydroxide and iron trichloride) is not subject to classification and labelling for acute toxic effects according to Regulation 1272/2008/EC.