Registration Dossier

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
Study period:
28 April to 12 May 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study, equivalent to guidelines available at the time of study; on related material

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trisodium EDDS (under code)
- Molecular formula (if other than submission substance): C10-H13-N2-O8. 3Na
- Molecular weight (if other than submission substance): 358
- Smiles notation (if other than submission substance): [Na+].[Na+].[Na+].OC(=O)[C@H](CC([O-])=O)NCCNC(CC([O-])=O)C([O-])=O
- Substance type: technical product
- Physical state: white, granular powder
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River USA, Portage, Michigan, USA
- Age at study initiation: males, 7 weeks; females, 9 weeks
- Weight at study initiation: males, 212-229 g; females, 201-218 g
- Fasting period before study: no
- Housing: polypropylene cages with wire mesh tops and floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 35-65 (except on 7 days when low values were recorded)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright dust generator
- Exposure chamber volume: 120 L
- Method of holding animals in test chamber: held in stainless steel mesh cages partitioned to provide 10 individual animal compartments
- Source and rate of air: compressed air, 25 L/min
- Method of conditioning air: no data
- System of generating particulates/aerosols: test substance packed into the Wright dust generator using a hydraulic bench press; even density was achieved by packing the generator in stages and applying a 1.0 ton weight. The test atmosphere was generated by resuspending the test substance scraped from the surface of the compressed powder in a stream of dry air
- Method of particle size determination: air samples taken using an Andersen mini-sampler and the collected material was weighed to detemine the particle size distribution
- Treatment of exhaust air: passed out through small holes in chamber to extraction system
- Temperature, humidity, pressure in air chamber: air temperature measured at 30 min intervals and found to be 23oC; relative humidity was measured using a water vapour analyser every 30 min and found to have a mean of 62.3% (mean 43.1% for the control group)

TEST ATMOSPHERE
- Brief description of analytical method used: no data
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 22% was 5.5 um or less in aerodynamic size (respirable size)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): no data

Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
1.49 mg/L of air (highest attainable concentration using the methods described)
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: observed continuously during exposure and at least twice daily until study termination. Body weights recorded on day of exposure and days 1, 3, 7 and 14 of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights of lungs, liver and kidneys
Statistics:
Analysis of variance was carried out on the lung, liver and kidney weights. Body weights were compared using Student's "t" distribution

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 490 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: CLs not applicable
Mortality:
None
Clinical signs:
other: Signs consistent with exposure to an irritant dust (eye squint, salivation and restless behaviour) were observed during treatment, but had disappeared within an hour post-exposure.
Body weight:
Body weights were not significantly different compared to the control groups.
Gross pathology:
No abnormalities were detected on macroscopic examination.
Other findings:
Lung, liver and kidney weights were comparable to the controls.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a GLP study conducted according to OECD Guideline 403 (available at the time), an acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3; the highest attainable concentration) in air was determined for trisodium EDDS in male and female rats following whole body exposure.




Executive summary:

In a GLP study conducted according to OECD Guideline 403 (available at the time), the acute inhalation toxicity of trisodium EDDS was assessed in a study on male and female rats. Groups of five rats of each sex were exposed continuously (by whole body contact) to air containing 0 or 1.49 mg trisodium EDDS/L for 4 h. The animals were then observed for a 14-day period for mortality, clinical signs of toxicity and changes in body weight before being examined macroscopically for gross abnormalities and for differences in the lung, liver and kidney weights compared to the controls.

No deaths occurred during the study and no clinical signs of toxicity were evident. Although eye squint, salivation and restless behaviour was observed in the treated groups (consistent with exposure to an irritant dust) these had disappeared within 1 h post-treatment. The test substance remained on the fur of the exposed groups. Body weights were not significantly different compared to the control groups; at necropsy there were no abnormal findings and the lung, liver and kidney weights were comparable to those of the controls.

An acute inhalation 4-h LC50 value of >1.49 mg/L (about 1490 mg/m3) in air was determined for trisodium EDDS in male and female rats following whole body exposure. According to EU CLP and DSD regulations, trisodium EDDS would not be classiffied as acutely toxic by the inhalation route under the conditions of this test.

[Data on trisodium EDDS is considered relevant to use for understanding the potential acute toxicity, inhalation of EDDS acid, and is acceptable for using as read-across information].