Registration Dossier

Administrative data

Description of key information

Oral, rat (similar or equivalent to OECD 401): LD50 > 1780 < 2000 mg/kg bw (read- across from tetrasodium EDTA)

Inhalation , rat (OECD 412): LOAEC 30 mg/m3 (read-across from disodium dihydrogen EDTA)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to analogue justification provided in IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
reference to other study
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 780 - < 2 000 mg/kg bw
Remarks on result:
other: source: CAS 64-02-8, BASF AG, 1983, rat
Sex:
male
Dose descriptor:
LD50
Effect level:
1 913 mg/kg bw
Remarks on result:
other: source: CAS 64-02-8, BASF AG, 1983, rat
Sex:
female
Dose descriptor:
LD50
Effect level:
1 780 mg/kg bw
Remarks on result:
other: source: CAS 64-02-8, BASF AG, 1983, rat

In an acute oral toxicity study performed with the read-across substance disodium hydrogen EDTA (CAS 139 -33 -3) by BASF (1973), single doses of 2500, 3200, 4000, 5000 and 6400 mg/kg bw Na2EDTA were administered by gavage to male and female rats as 30% solution in carboxymethyl cellulose solution. The dose groups consisted of 5 males and 5 females each and the animals were observed for 7 days. The LD50 was found to be 2800 mg/kg bw. Clinical symptoms were accelerated respiration, squatting posture, contaminated fur, intermittened respiration, reluctance to move. Autopsy of animals which died revealed dilatation of the heart and stomach as well as diarrhoea like content in the gut, congestion of the liver and degeneration of the kidney. The animals which were sacrificed showed no abnormalities during necropsy. For reasons of a conservative (worst case) assessment approach data these data were not used for risk assessment and classification.

An LD50 in rats of >= 4000 - <= 8000 mg/kg bw was determined for the target substance trisodium EDTA (cited in CIR, 2002). However, as no further details on the study design were available, this information was not considered for classification/non-classification.

Interpretation of results:
other: CLP/GHS criteria met; classification required as Acute Tox. 4, H302 according to Regulation (EC) No. 1272/2008
Conclusions:
An acute oral toxicity study in rats with the source substance tetrasodium EDTA (CAS 64-02-8) was selected as key result for reasons of structural similarity, data reliability and for reasons of a conservative (worst case) risk assessment approach.
The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their acute oral toxicity potential. The combined LD50 for male and female rats for the source substance tetrasodium EDTA was determined to be > 1780 < 2000 mg/kg bw. For this substance (CAS 64-02-8) there exists also a CLP harmonized classification as Acute Tox. 4, H302. Therefore, an acute toxicity potential is also expected for the target substance trisodium hydrogen EDTA (CAS 150-38-9).

CLP: Acute Tox. 4, H302
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 780 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on (bio)transformation to common compounds (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

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
Justification for type of information:
Refer to analogue justification provided in IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male
Dose descriptor:
other: LOAEC
Effect level:
ca. 30 mg/m³ air
Based on:
act. ingr.
Remarks:
Na2H2EDTA
Remarks on result:
other: Basis for effect level: histopathology of the respiratory tract and lung weights
Remarks:
; source: CAS 139-33-3, BASF SE, 2010, rat
Interpretation of results:
other: CLP/GHS criteria met; classification required as Acute Tox 4, H332 according to Regulation (EC) No. 1272/2008
Conclusions:
The acute inhalation toxicity study with the source substance disodium dihydrogen EDTA (CAS 139-33-3) was selected as key result for reasons of structural similarity and data reliability.
The read across approach is justified in the analogue justification. The target and source substance are considered unlikely to differ in their acute inhalation toxicity potential. The acute inhalation LOAC was found to be 30 mg/m3 for the source substance. Therefore, an acute LOAC of 30 mg/m3 air was considered for the hazard assessment and C&L purposes for the target substance trisodium hydrogen EDTA (CAS 150-38-8).

CLP: Acute Tox 4, H332
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on (bio)transformation to common compounds (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no experimental data available regarding the acute toxicity of trisodium hydrogen EDTA (CAS 150-38-9). Thus, read-across from appropriate source substances (disodium dihydrogen EDTA, CAS 139-33-3 and tetrasodium EDTA, CAS 64 -02 -8) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VII and VIII, 8.5. (Bio)transformation to common compounds of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Oral

In an acute oral toxicity study conducted by BASF AG (1983) single doses of 1210, 1780, 2000, 2610 mg/kg bw tetrasodium EDTA were administered by gavage to male and females rats as 12 - 26% solution in water. The dose groups consisted of 10 males and 10 females each which were fasted 16 h prior to the experiment. After administration a 14 day observation period followed. The LD50 was found to be between 1780 and 2000 mg/kg bw (1913 mg/kg bw males; 1780 mg/kg bw females). The clinical symptoms consisted of dyspnea, apathy, ataxia, abnormal positions, spastic gait, exiccosis, diarrhea, shaggy fur, saliva and a poor general state in the higher dose groups additionally diarrhea. At necropsy, findings in the animals that died comprised of redness and/or bloody ulceration of the glandular part of the stomach, redness of the mucous membrane of the stomach and gut as well as general hyperemia and bloody mucous content of the gut. No macroscopic abnormalities were observed in the surviving animals at the end of the study.

In an acute oral toxicity study performed with the read-across substance disodium dihydrogen EDTA (CAS 139 -33 -3) by BASF (1973), single doses of 2500, 3200, 4000, 5000 and 6400 mg/kg bw disodium hydrogen EDTA were administered by gavage to male and female rats as 30% solution in carboxymethyl cellulose solution. The dose groups consisted of 5 males and 5 females each and the animals were observed for 7 days. The LD50 was found to be 2800 mg/kg bw. Clinical symptoms were accelerated respiration, squatting posture, contaminated fur, intermittened respiration, reluctance to move. Autopsy of animals which died revealed dilatation of the heart and stomach as well as diarrhoea like content in the gut, congestion of the liver and degeneration of the kidney. The animals which were sacrificed showed no abnormalities during necropsy.

An LD50 in rats of >= 4000 - <= 8000 mg/kg bw was determined and is cited for the target substance trisodium EDTA (CIR, 2002). However, as no further details on the study design were available, this information was not considered for classification/non-classification.

Inhalation

In a subacute repeated dose toxicity study (BASF SE, 2010) 10 male Wistar rats per dose were exposed to a respirable dust aerosol of disodium dihydrogen EDTA (CAS 139 -33-3) for 6 hours per day for 5 consecutive days at concentrations of 0, 30, 300, 1000 mg/m³ air. Exposure in the high dose group (1000 mg/m3) was for one day only due to mortality observed. Inhalation exposure to 1000 mg/m³ disodium dihydrogen EDTA for 6 hours caused lethality in 6 out of 20 male rats. Histological examination of the lung of the dead rats revealed congestion, edema, multifocal hemorraghes and inflammatory cell infiltrates. Inhalation exposure of rats to disodium dihydrogen EDTA for 6 hours per day, 5 consecutive days cause concentration dependant lesions in the larynx and lungs that were fully reversible within 14 days. Due to histopahological changes in the low dose group a no observed effect level could not be determined. The LOAEC was considered to be 30 mg/m³ air.

Justification for classification or non-classification

Based on read-across, the available data on acute oral toxicity meet the criteria for classification according to Regulation (EC) No. 1272/2008 as Acute Tox. 4 (H302).

Based on read-across, the available data on acute inhalation toxicity meet the criteria for classification according to Regulation (EC) No. 1272/2008 as Acute Tox. 4 (H332).