Pentasodium (carboxylatomethyl)iminobis(ethylenenitrilo)tetraacetate

Endpoint summary

Description of key information

Oral: 1 acute oral study using DTPA acid; 4 acute oral studies using pentasodium DTPA; 2 acute oral studies using pentapotassium DTPA.
Dermal: 1 acute dermal study using pentapotassium DTPA
Inhalation: 1 acute inhalation study using pentasodium DTPA; 1 sub-acute inhalation study using Disodium EDTA (read across)

Additional information

The acute oral toxicity of DTPA is low, with LD50 values for the acid and the salt in excess of 2000 mg/kg bw/day. Limited details are available from the studies regarding the potential cause of mortality, however some of the studies did indicate some apparent effects on the kidneys and liver. There is very little difference in the toxicity associated with the pentapotassium, pentasodium salts of DTPA and the acid when one considers the amount of DTPA provided per dose of each substance.

The acute dermal toxicity of DTPA acid and the sodium and potassium salts is very low (LD50 >2000 mg/kg bw). This is consistent with the fact that the dermal penetration of DTPA is very low (<0.1%), as such, dermal dosing of this material will not result in a high enough systemic dose to produce overt toxicity or mortality.

Acute inhalation summary:

 

DTPA acid, potassium and sodium salts are not volatile. Therefore the potential for acute inhalation exposure to vapors of these substances is remote. In a study performed using Pentasodium DTPA, rats exposed for 8 hours to the vapour generated at room temperature did not suffer any adverse effects. (There was however no measurement of the actual amount of DTPA in the air in that study). Acute inhalation exposure to the solid form of these materials is self limiting due to the particle sizes of the powders (90% >60 micrometers diameter) which will significantly limit the amount inhaled and delivered to the respiratory tract. However, an inhalation study performed using the powder form of disodium EDTA (refer to repeated dose inhalation studies) did result in 6 deaths out of 20 male rats following a single 6 hour exposure to 1000 mg/m3 disodium EDTA. The test material used in this study was processed to achieve a MMAD of approximately 2 micrometers. Therefore this would constitute a worst case exposure situation where 100% of the test material was respirable. In the remaining 14 animals there were no adverse effects reported at necropsy following a 14 day observation period. Therefore these effects were fully reversible within the observation period.

The toxicity observed in the study is considered to be due to the chelating agent complexing calcium within cells of the alveoli and terminal bronchioles following its impaction there. This leads to the break down of epithelial membranes and leads to the edema and congestion observed which ultimately led to deaths. As this toxicity is related to chelation of metals such as calcium locally in the lung it is considered it would be relevant to DTPA acid, Pentasodium DTPA and pentapotassium DTPA since each of these has a similar affinity for calcium compared to EDTA.

Justification for classification or non-classification

Oral and Dermal Acute toxicity: No classification is required.

Inhalation:

The toxicity observed in the inhalation study conducted using the read across substance, disodium EDTA, indicates that classification for acute inhalation toxicity may be warranted. In the study the particle size of the test material was approximately 2 micrometers (MMAD). In commercial DTPA acid and Pentasodium DTPA powder the average particle size is >100 micrometers, with typically less then 4% having a size less than 10 micrometers in diameter. As such the concentration of commercial powder in the air that would be required to produce the lethality seen in the inhalation study would be more than 20 times higher (>20000 mg/m3). Thus the commercially produced powders would not pose an acute inhalation hazard. However it is possible that users could process the powder further or produce concentrated liquid aerosols with a smaller, respirable particle size. In these situations DTPA could pose an acute inhalation hazard, if the concentration dosed to the lungs were sufficient.

Considering the data available, exposure for 6 hours to a concentration of 1000 mg/m3 disodium EDTA produced 6 deaths in 20 animals. DTPA would be considered to have equivalent potency due to similar chelating constants for calcium. The cut off for classification of a dust/aerosol as harmful is an LC50 between 1000 and 5000 mg/m3 for an inhalation exposure for 4 hours. In the study the exposure period was for 6 hours, however it is likely that an exposure to a concentration between 1000 and 5000 mg/m3 for 4 hours could have resulted result in at least 50% of the animals dying. Therefore it is considered appropriate to classify this substance as Acute Inhalation Category 4 according to the CLP regulation; R20, Harmful via inhalation, according to the DSD.