Dipraseodymium trioxide

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

1

Absorption rate - dermal (%):

1

Absorption rate - inhalation (%):

2

Additional information

Introduction

Physico-chemical properties of dipraseodymium trioxide (EC 234-845-3, CAS 12036-32-7) and the results of in vitro and in vivo studies conducted with dipraseodymium trioxide, or the read across substances praseodymium III, IV oxide (EC 234-857-9, CAS 12037-29-5) and dipraseodymium tricarbonate (EC 227-578-9, CAS 5895-45-4), have been used to determine, as far as possible, a toxicokinetic profile.

Physicochemical properties

The substance dipraseodymium trioxideis a pale green solid(Tremain 2017)and has the molecular formula Pr₂O₃with a molecular weight of 329,81g/mol. It is insoluble in water (reported to be <1g/L or 0.2 mg/L in cold water) and has a pH of 8.54. As dipraseodymium trioxide is an inorganic substance with a melting point of >300°C, no partition coefficient or vapour pressure have been determined.

The read across substances praseodymium III oxide (molecular formula: PrO₂, appearance: brown powder, molecular weight: 172.91 g/mol) and dipraseodymium tricarbonate (molecular formula: Pr₂(CO)₃, appearance: green powder, molecular weight: 461.85) are slightly soluble in water at approximately 1 to 2 g/L. 

Absorption

Oral absorption

In acute oral toxicity studies, the acute median lethal dose (LD₅₀) of both read across substances (praseodymium III, IV oxide and dipraseodymium tricarbonate) was estimated to be >2000 mg/kg body weight. There were no signs of systemic toxicity or abnormalities at necropsy and animals gained weight as expected.

The read across substance, praseodymium III, IV oxide, was tested in a combined repeated dose toxicity study with reproduction/developmental toxicity screening test performed according to the OECD TG 422 (1996). There were no treatment-related clinical signs of toxicity, reductions in body weight or food consumption, changes in organ weights or histopathology findings at any dose level. In addition, there were no adverse findings with respect to reproductive/developmental toxicity. There were some, limited changes in clinical pathology parameters: mean haemoglobin concentration, red blood cell counts and haematocrit were slightly lower than the concurrent control and mean red cell distribution width values and reticulocyte counts were slightly higher at all dose levels in lactating females; mean lactate dehydrogenase activities were lower than the control at all dose levels in males at Week 4 of study and in females during lactation; mean phosphate and calcium levels were also higher than the control during lactation in females receiving 300 or 1000 mg/kg/day. However, given that these clinical pathology changes were without pathological correlates and that the changes did not manifest themselves clinically, they were considered not to be adverse. Overall the no observed adverse effect level (NOAEL) was defined as 1000 mg/kg bw/day.

The available in vivo read across data, suggests that oral absorption of dipraseodymium trioxide is unlikely. This is supported by the physio-chemical properties of the substance; the substance is insoluble in water and the majority of particles are >1 µm in size, therefore absorption from the gastrointestinal tract or uptake by pinocytosis is unlikely. Therefore, for the purposes of risk assessment oral absorption is assumed to be 1%.

Dermal absorption

No dermal toxicity data are available for dipraseodymium trioxide or the read across substances. Some toxicokinetic information can be inferred from thein vitroirritation and corrosion studies on the substance. Dipraseodymium trioxide did not cause any skin corrosion or skin irritation in vitro (GLP studies performed according to OECD TG 431. In addition, in in vivoskin sensitisation studies (GLP OECD 429 local lymph node assay) dermal administration of suspensions of each read across substance at up to 25% w/w did not cause skin sensitisation. These data support a lack of absorption through the skin.

The test substance is inorganic in nature and highly insoluble, it is not expected to be lipophilic. Therefore, it can be concluded that any absorption via the dermal route is unlikely and for the purposes of DNEL setting, dermal absorption is estimated at 1%.

Inhalation absorption

Data on acute toxicity by inhalation for praseodymium III, IV oxide and dipraseodymium tricarbonate are available. 

Inhalation of praseodymium III, IV oxide at 5.21 mg/L resulted in an increased respiratory rate in all animals both during and shortly after exposure and which continued until Day 7 or 8 post-exposure when all animals returned to a normal state. All animals exhibited bodyweight losses or showed no bodyweight gain on the first day post-exposure, but by Day 4 post-exposure all animals exhibited bodyweight gains. No deaths occurred throughout the study and macroscopic abnormalities were limited to dark patches on the lungs at necropsy. The 4 hour LC₅₀was therefore determined to be > 5.21 mg/L.

Inhalation of dipraseodymium tricarbonate at 5.25 mg/L resulted in an increased respiratory rate in all animals both during and shortly after exposure. One day after exposure, all animals exhibited increased respiratory rate and hunched posture, piloerection was also apparent in some females. Animals recovered to appear normal from Days 5 to 9 post-exposure. Most animals exhibited bodyweight losses or showed no bodyweight gain on the first day post-exposure, but by Day 4 post-exposure all animals exhibited bodyweight gains. No deaths occurred throughout the study and no macroscopic abnormalities were detected at necropsy. The 4 hour LC₅₀was therefore determined to be > 5.25 mg/L.

Based on the lack of systemic effects following 4-h inhalation of the read across substances at the highest technically achievable concentrations of approximately 5 mg/L, inhalation absorption at 2% (i.e. twice the oral absorption) is assumed for risk assessment purposes.

Distribution, Metabolism and Elimination

No information is available to describe the distribution, metabolism or elimination of the material.

The moderate molecular weight and water insolubility of the substance would suggest that diffusion across lipid membranes would be slow and therefore wide distribution is unlikely.

Given the water insolubility and small particle size (D10 = 0.2 µm, D50 = 2.1 µm) of the substance there is the potential for limited accumulation in the lungs of any inhaled material.

No information is available on the fate of the possibly absorbed material however, given the nature of the substance and its physico-chemical properties, no metabolism is expected to occur.

As there is unlikely to be any oral absorption, ingested material is likely to pass through the gastrointestinal tract and be eliminated in the faeces.

Conclusions

Based on in vitro and in vivo data from studies performed with dipraseodymium trioxide or the read across substances praseodymium III, IV oxide and dipraseodymium tricarbonate, oral absorption is estimated at 1%, inhalation absorption is estimated at 2% and dermal absorption is estimated at 1%. 

The potential for bioaccumulation is considered low.

References

Bradshaw, J. 2012. “Dipraseodymium tricarbonate: ACUTE ORAL TOXICITY IN THE RAT- FIXED DOSE METHOD.”

Clouzeau, J. 1994. “Acute Oral Toxicity in Rats.”

Flatschacher. 2017. “Dipraseodymium trioxide analytical report.”

Griffiths, DR. 2012b. “Dipraseodymium tricarbonate: ACUTE INHALATION TOXICITY (NOSE ONLY) STUDY IN THE RAT.”

Griffiths, DR. 2012a. “Praseodymium III, IV, oxide: ACUTE INHALATION TOXICITY (NOSE ONLY) STUDY IN THE RAT.”

Henzell, G. 2012b. “Dipraseodymium tricarbonate: LOCAL LYMPH NODE ASSAY IN THE MOUSE .”

Henzell, G. 2012a. “Praseodymium III,IV oxide: LOCAL LYMPH NODE ASSAY IN THE MOUSE.”

Lacey, FE. 2017b. “Dipraseodymium Trioxide: Determination of Skin Irritation Potential using the EPISKIN™ Reconstructed Human Epidermis Model.”

Lacey, FE. 2017a. “Dipraseodymium Trioxide: In vitro EPIDERM™ Skin Corrosion Test.”

Lide, SP, et al. 1995.CRC Handbook of Chemistry and Physics 1994-1995 75th Edition.CRC Press.

Tremain, SP. 2017. “Dipraseodymium Trioxide: Determination of Hazardous Physico-Chemical Properties.”

Wallace, I. 2013. “A Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening of Praseodymium (III, IV) Oxide by Oral Gavage in Rats.”