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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Remarks:
testing lab.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
purity 93%
impurities: < 7% water; < 3% sodium glycolate; 2% disodium irninodi(acetate); < 2% sodium hydroxide; < 1.5% methanamine; < 1 % sodium formate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
other: water
Details on inhalation exposure:
The objective of this study in rats was to provide data on the sensory irritation of Trisodium Nitrilotriacetate (NTA) by means of the Alarie test in Wistar rats. Although the sensory irritation test onginally was developed for mice, section 7.1.3 of guideline ASTM E981-04 (see below) indicates that the same system can be used with guinea pigs or rats. In addition, by using rats in the sensory irritation test, it will be easier to
link these data to data obtained from acute and subacute inhalation toxicity studies with NTA. In addition, mice are much better able to reduce their minute breathing volume and cope with the increased blood CO2 concentration than either rats or humans. Data from rats may therefore be more relevant for extrapolation to humans than data from mice.
Duration of exposure:
30 min
Concentrations:
0.91 mg/L (low concentration group), 2.86 mg/L (mid concentration group) and 4.25 mg/L (high concentration group)
Control animals:
yes

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
other: RD50
Effect level:
4.25 mg/L air
Exp. duration:
30 min

Any other information on results incl. tables

Exposure to the test material at all concentrations resulted in a change in breathing pattem characterised by an irregular breathing pattem. These consisted of normal breathing intermingled with periods of irregular breathing. However, post-inspiratory apnoeas, characteristic for sensory imtation, were only observed in one out of four animals exposed to 2.86 mg/L and in two out of four animals exposed to 4.25 mg/L. Clinical signs were not seen during the 7-day post-exposure period. Mean body weight gain was low from day 0 to day 3, whereas from day 3 to day 7 body weight gain was considered to be within a normal range for animals of this strain and age. Absolute and relative lung weights of the exposed animals were considered to be normal for animals of this strain and age. Abnormalities were not observed at necropsy 7 days after exposure.

Overall, the results of this study show sensory imtation to be present in rats at levels of 2.86 and 4.25 mg/L NTA. The RD50 value was estimated to be close to 4.25 mg/L. Although there was high inter-individual variability in responses amongst the rats, these results suggest that sensory irritation is confined to high exposure levels, close to the technically highest attainable concentration. Sensory imtation was absent at a level of 0.91 mg/L NTA.

Applicant's summary and conclusion