Dipotassium dihydrogen ethylenediaminetetraacetate

Endpoint summary

Description of key information

An acute oral toxicity study has not been conducted on K2EDTA. However, the acute oral LD50 of edetic acid in rats was found to be 4500 mg/kg bw (BASF 1973).
K2EDTA is not acutely toxic via the inhalation route. In a OECD 403 guideline compliant acute inhalation study in F344 rats, acute exposure to K2EDTA for 4hours resulted in an LC50 of >5.80mg/L.
Furthermore it is highly unlikely that K2EDTA would be acutely toxic via the dermal route as K salts of EDTA are unable to penetrate the skin with data generated in humans indicating 0.001% of the total dose is absorbed.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles (non-GLP)

Justification for type of information:

Read across is based on a structurally similar material. An analogue justification is attached in section 13 of dataset.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

BASF-TEST: In principle, the methods described in the OECD Guideline 401 were used. Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean body weight at study initiation: males: 264 g; females: 274 g

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

DOSAGE PREPARATION
- Stock solution prepared: 30%
- Dose volume applied: 10.66 ml/kg bw for the 3200 mg/kg bw dose group; 13.33 ml/kg bw for the 4000 mg/kg bw dose group; 16.66 ml/kg bw for the 5000 mg/kg bw dose group; 21.4 ml/kg bw for the 6400 mg/kg bw dose group; 26.6 ml/kg bw for the 8000 mg/kg bw dose group; 33.3 ml/kg bw for the 10000 mg/kg bw dose group.

Doses:

3200; 4000; 5000; 6400; 8000; 10000 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;
- The animals were observed for mortality and clinical signs of toxicity;
- Frequency of observations: Several times on the application day, thereafter once each working day;
- Body weights were only recorded at the beginning of the study;
- Necropsy of survivors and animals which died performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Mortality:

1/10 died in the 3200 mg/kg bw dose group, 3/10 died in the 4000 mg/kg bw dose group, 6/10 died in the 5000 mg/kg bw dose group, 8/10 died in the 6400 mg/kg bw dose group, 9/10 died in the 8000 mg/kg bw dose group, 10/ 10 died in the 10000 mg/kg bw dose group (See table 1).

Clinical signs:

other: 3200 mg/kg bw and 4000 mg/kg bw dose group: directly after application accelerated respiration, squatting posture, red eyes; 1 day later: squatting posture, aggressiveness, contaminated fur, slight diarrhea; 5 days later: aggressiveness, contaminated fur;

Gross pathology:

Animals which died:
10000 mg/kg bw dose group: heart: acute dilatation, venous hyperemia; kidneys: muddy gray
Remaining dose groups: heart: acute dilatation particularly right, venous hyperemia; stomach: dilatated, dry hard content, bloody ulceration in the corpus; gut: diarrhea,
Animals sacrificed:
-nothing abnormal detected

Table 1: Mortalities of rats after oral application of EDTA

		3200 mg/kg bw	4000 mg/kg bw	5000 mg/kg bw	6400 mg/kg bw	8000 mg/kg bw	10000 mg/kg bw
1 h	male	0/5	0/5	0/5	0/5	0/5	0/5
	female	0/5	0/5	0/5	0/5	0/5	0/5
24 h	male	0/5	0/5	0/5	0/5	1/5	5/5
	female	0/5	0/5	0/5	0/5	1/5	5/5
48 h	male	0/5	0/5	0/5	1/5	1/5	5/5
	female	0/5	0/5	0/5	1/5	1/5	5/5
7 d	male	1/5	3/5	5/5	5/5	5/5	5/5
	female	0/5	0/5	0/5	3/5	4/5	5/5
14 d	male	1/5	3/5	5/5	5/5	5/5	5/5
	female	0/5	0/5	1/5	3/5	4/5	5/5

Endpoint conclusion

Dose descriptor:

LD50

Value:

4 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5.8

Additional information

Oral route:

In the key study conducted by BASF AG (1973) single doses of 3200, 4000, 5000, 6400, 8000 and 10000 mg/kg bw edetic acid were administered by gavage to male and females 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 14 days. The LC50 was found to be 4500 mg/kg bw. Clinical symptoms were: squatting posture, aggressiveness, diarrhea and contaminated fur in all dose group. Autopsy of the animals which died revealed acute heart dilatation, bloody ulceration of the stomach and soft to fluid contents of the intestine.

An additional acute oral toxicity study (Akzo Chemicals, 1987) obtained a LD50 > 2000 mg/kg bw for male and female rats. No clinical signs or autopsy findings have been reported up to 2000 mg/kg bw.

Inhalation route:

In the key study conducted by Dow (2016) Groups of five rats/sex were exposed for four hours, using a nose-only inhalation exposure system, to a time-weighted average chamber concentration of 5.80 mg PRIVENTZ™ Liquid per liter of air. The mass median aerodynamic diameter (MMAD) of the PRIVENTZ™ Liquid aerosol present in the exposure chamber test atmosphere averaged 2.17 microns with an average geometric standard deviation of 2.19 microns.

All animals survived the four-hour exposure to the test material as well as the 14-day postexposure period. Clinical effects noted during the four-hour exposure period were limited to soiling of the haircoat in 2/5 male and 3/5 female rats. In-life observations noted postexposure included perineal soiling in 5/5 female rats and extensive body soiling in 2/5 female rats. All rats appeared normal by test day 5. Mean body weight losses of 3.3 and 2.1% were noted for male and female rats, respectively, on test day 2. Pre-exposure mean body weight values were exceeded on test day 8. There were no visible treatment-related lesions noted in any of the rats exposed to PRIVENTZ™ Liquid at the test day 15-scheduled necropsy. Nontreatment related visible lesions noted at necropsy were limited to necrotic fat in one male rat.

Based on these data, the four-hour LC50 of inhaled, aerosolized PRIVENTZ™ Liquid exceeded the limit test concentration of 5 mg/L and is greater than 5.80 mg/L for male and female F344/DuCrl rats.

Justification for classification or non-classification

Based on the results obtained in the toxicity studies and taking into account the provisions laid down in Regulation EC 1272/2008, a classification has not to be done with respect to acute oral, dermal or inhalation toxicity.