Triammonium hydrogen ethylenediaminetetraacetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study, GLP For read-across justification refer to section 13.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 412 (Repeated Dose Inhalation Toxicity: 28/14-Day)

Deviations:

yes

Remarks:

Dosing until day 5 only

GLP compliance:

yes (incl. QA statement)

Test type:

other: subacute

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Na2H2EDTA

IUPAC Name:

Na2H2EDTA

Constituent 2

Reference substance name:

Disodium dihydrogen ethylenediaminetetraacetate

EC Number:

205-358-3

EC Name:

Disodium dihydrogen ethylenediaminetetraacetate

Cas Number:

139-33-3

IUPAC Name:

disodium dihydrogen 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Constituent 3

Reference substance name:

Disodium ethylene diamine tetraacetic acid

IUPAC Name:

Disodium ethylene diamine tetraacetic acid

Details on test material:

Trilon BD
Batch Number: 06088797V0
Purity 91.7% (W/W%)
Expiry date: 01 September 2011
Solid white powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Age: 7 weeks (approx)
Identification: Tattooing of ears
All animals free of disease and clinical signs
Rats housed together (5 animals per cage) in Polysulfon cages
Bedding: Type Lignocel fibres, dust free bedding
Woodne gnawing blocks for enrichment
Rooms: Fully ariconditioned, temperature range 20 to 24 degrees celcius, 30 to 70% humidity
Light/dark cycle of 12 hours (6 am to 6pm light, 6pm to 6 am dark)
Food, drinking water and bedding/enrichment materials were analysed for chemical and microbiological contaminants.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

A dust aerosol was generated using a dust generator and compressed air inside a mixing stage mixed with conditioned dilution air and passed into the inhalation system. The test substance was mixed with Aerosil R972 prior to facilitate aerosol generation.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Concentrations of the inhalation atmospheres were analyzed using gravimetry. Daily means were calculated based on 2 measured samples per concentration and exposure. From the Daily mean values of each concentration, mean concentrations and standard deviati

Duration of exposure:

6 h

Remarks on duration:

per day, 5 consecutive days

Concentrations:

- 30, 300, 1000 mg/m³ (nominal conc. of Na2H2EDTA)
- 33.3 (+/-2.3), 320 (+/-27), 1103 (+/-52) mg/m3 (measured (with SD) referring to test substance Na2H2EDTA x 2 H2O)

No. of animals per sex per dose:

10 animals per dose group
An additional 10 animals for the high dose group and control

Control animals:

yes

Details on study design:

The animals were exposed to a respirable dust aerosol for 6 hours per day for 5 consecutive days. The exception was the high dose group (1000mg/m3) where exposure was for one day only due to mortality observed.

Statistics:

Body weight/body weight change, food consumption - comparison of each group with control using DUNNETTS test (two-sided) for the hypothesis of equal means
Clinical pathology, urine volumes, urine specific gravity, Weight parameters - Non-parametric one-way analysis using Kruskal-wallis test (two sided). If resulting p-value was less than 0.05, a pairwise comparison of each dose group with the control group was performed using Wilcoxon-test (two sided) for equal means.

Results and discussion

Effect levels

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

Mortality:

6 deaths in the high dose group on days 0 and 1. Accelerated respiration, respiration sounds, piloerection, red encrusted nose, hunched position; Mid dose group - accelerated respiration, respiration sounds, piloerection, reduced fur care

Clinical signs:

other: 6 deaths in the high dose group on days 0 and 1. Accelerated respiration, respiration sounds, piloerection, red encrusted nose, hunched position; Mid dose group - accelerated respiration, respiration sounds, piloerection, reduced fur care

Body weight:

Decreased bodyweight change in mid and high dose group

Gross pathology:

Congestion, edema and multifocal hemorraghes in lungs of high dose group

Other findings:

FOOD CONSUMPTION
- decreased food consumption between days 0 and 1 in mid and high dose group

ORGAN WEIGHTS
- Lung weight increase in low and mid dose group

Any other information on results incl. tables

Detials on Results

Histopathology results:

High dose: Multifocal hemorraghes in the lungs; Inflammatory cell infiltrates

Mid dose:

Larynx: laryngeal, epithelial necrosis, multifocal, in various levels of the larynx

Inflammatory cell infiltrates in various levels of the larynx

laryngeal squamous metaplasia, multifocal, in various levels of the larynx

Regenerative hyperplasia of the laryngeal epithelium, multifocal, in various levels of the larynx

Lungs: Regenerative hyperplasia of bronchiolar epithelium (predominantly: medium bronchi, terminal bronchioles)

Mucous cell hyperplasia in large bronchi

interstitial infiltration of eosinophylic granulocytic cells

Low dose:

Larynx: Laryngeal, epithelial necrosis, multifocal, at the base of the epiglittis (level 1)

Inflammatory cell infiltrates at the base of the epiglottis (level 1)

Lungs: Regenerative hyperplasia of the bronchiolar epithelium (predominantly medium bronchi and terminal bronchioles)

Mucous cell hyperplasia in large bronchi

interstitial infiltration of eosinophylic granulocytic cells.

There were no histopathological findings in any of the recovery group animals. Thus all pathology was reversible within the recovery period.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information

Conclusions:

Inhalation exposure to 1000 mg/m3 disodium 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 EDTA for 6 hours per day, 5 consecutive days cause concentration dependant lesions inthe larynx and lungs that were fully reversible within 14 days. Due to histopahological changes in the low dosegroup a no observed effect level could not be determined.

Executive summary:

In a subacute repeated dose toxicity study (BASF, 2009) 10 male Wistar rats per dose were exposed to a respirable dust aerosol of Na2H2EDTA for 6 hours per day for 5 consecutive days at concentrations of 0, 30, 300, 1000 mg/m³ air (also see capter 7.5).

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 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 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.