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Acute Toxicity: inhalation

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acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment (pre-OECD /pre-GLP study)
Reason / purpose:
reference to same study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
no guideline available
Principles of method if other than guideline:
Ten male albino rats per dose were exposed to micronised NTA at four dose levels, followed by a 14 day observation period and were necropsied afterwards. Mortality and clinical signs were observed during exposure and post exposure period.
GLP compliance:
(pre-GLP study)
Test type:
standard acute method
Limit test:

Test material

Details on test material:
- Substance type: pure substance
- Physical state: solid, finely divided powder, pale yellow in colour
- Analytical purity: no data

Test animals

Details on test animals and environmental conditions:
- test animals: male Sprague Dawley albino rats
- Source: no data
- Weight at study initiation: 243-293 g

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Details on inhalation exposure:
- Exposure apparatus: glass inhalation chamber
- Exposure chamber volume: 38-liter
- Method of holding animals in test chamber: no data
- System of generating particulates/aerosols: Wright dust Feed or pulse-puff generator
- Method of particle size determination: During certain exposures, atmospheric samples were obtained for aerosol particle size analysis with a Monsanto Cascade Impactor.

- Brief description of analytical method used: Chamber concentrations were determined gravimetrically during each exposure from every chamber by drawing known volumes of chamber atmosphere through glass fiber filters. The concentration was determined by dividing the quantity
(milligrams) of particulate collected by the total sample volume (liters). The concentration was expressed as mg/l.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution and mass median diameters:

Table 1: Particle size distribution from four-day inhalation exposures to XTW-448

Group No. Chamber Conc. mg/l Exposure day "particles < 10 µm
in diameter %" mass median diameter

4 0.174 2 63 8.0
3 83 5.2
5 2.307 1 64 8.2
2 79 4.6
4 72 7.3

Analytical verification of test atmosphere concentrations:
Duration of exposure:
ca. 6 h
Remarks on duration:
on consecutive days
Desired concentrations:
0, 0.002, 0.02, 0.2, 2.0 mg/l air
Actual chamber concentrations:
0, 0.003, 0.040, 0.174, 2.307 mg/l air
No. of animals per sex per dose:
groups of 10 male Sprague Dawley rats per dose
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights were recorded immediately prior to the first exposure (Day 1), and on Days 2, 3, 4, 5, 11, and 18
- Necropsy of survivors performed: yes. Necropsy of 5 animals on day 5 and 5 animals on day 18
- Other examinations performed: clinical signs were observed and recorded on days 1, 2, 3, 4 of exposure and at the end of the post exposure period, on day 18.
- no histopathology
no details described in the study
average values

Results and discussion

Effect levels
Dose descriptor:
Effect level:
2.307 mg/L air
Exp. duration:
4 d
Remarks on result:
other: no deaths; exposure: 6h/day
no mortality was observed neither during the exposure nor during the post exposure period.
Clinical signs:
other: The animals exposed to the three lower concentrations do not show any clinical signs like the control group. Animals exposed to 2.307 mg/l show clinical signs from the first day of exposure, but all signs disappeared till the end of the post exposure peri
Body weight:
no abnomalities (see table 2)
Gross pathology:
Necropsy: Generally, all tissues appeared normal when compared to those corresponding tissues from control animals.
Other findings:

Any other information on results incl. tables

Table 2: Development of bodyweight

Group No. body weight
day 1 day 2 day 3 day 4 day 5 day 11 day 18
1 (air control) 0.000 277 286 290 290 295 297 323
2 0.003 280 288 287 295 297 308 326
3 0.040 258 262 267 273 281 295 310
4 0.174 256 263 265 271 277 283 307
5 2.307 257 258 254 253 246 269 305

Clinical signs:

No clinical signs observed in the control group and in teh groups exposed to the three lower concentrations.

Clinical signs observed in the group exposed to 2.307 mg/l:

Day 1: All ten rats show salivation, hypoactivity and partially closed eyes. One rat showed a red area around eyes.

Day 2: All ten rats show salivation, hypoactivity, partially closed eyes, nasal exudate and brown crust around eyes. Furthermore three of them showed red area around eyes and nose.

Day 3: All ten rats show salivation, hypoactivity, partially closed eyes, nasal exudate and brown crust around eyes. Furthermore three of them showed red area around eyes and nose.

Day 4: All ten rats show salivation, hypoactivity, partially closed eyes, nasal exudate, brown crust around eyes and decreased rate of respiration. Furthermore three of them showed red area around eyes and nose.

Day 18: All clinical signs disappeared


Focal and diffuse areas of reddish-brown discoloration were observed on the surface of the lungs of both control rats and those exposed to all concentrations of XTW-448 at the Day 5 and Day 18 necropsy interval. It does not appear that this condition is compound-related; however, these findings will have to be correlated with the results of the microscopic examination of these tissues. Microscopic examinations are not published in this study. Generally, all tissues appeared normal when compared to those corresponding tissues from control animals.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Migrated information Criteria used for interpretation of results: not specified
No mortality was caused by exposure to Na3NTA. Clinical signs were evident at the highest concentration (2.307 mg/l) but disappeared until the end of the post exposure period.
Executive summary:

In a 4 -days repeated inhalation toxicity study 10 male Sprague Dawley rats per dose were exposed to Na3NTA for 6 hours per day (on consecutive days) at concentrations of0, 0.003, 0.040, 0.174, 2.307 mg/l (micronised NTA). Animals then were observed for 14 days.

No mortality was observed after treatment with NTA. All animals of the 2.307 mg/l group showed respiratory, nasal and eye irritation. Animals exposed to the lower concentrations did not show any clinical signs. Clinical signs disappeared within the observation period of 14 days after treatment. Gross observations at necropsy revealed no treatment-related abnormalities.