reaction mass of neodymium carbonate and praseodymium carbonate

Endpoint summary

Description of key information

Skin irritation / corrosion (based on the data on the reaction mass, and read-across approach with the main constituent of the reaction mass and three analogues): not irritating
Eye irritation (weight-of-evidence approach based on the data on both constituents and three analogues): not irritating 
Respiratory irritation: not formally assessed but not expected to be a respiratory irritant as the reaction mass is not classified as irritating to skin or eyes and there is no indication of irritant potential in acute oral/inhalation studies performed in rats with the reaction mass itself 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

 

The reaction mass of neodymium carbonate and praseodymium carbonate was a solid substance with a high melting point (> 450°C), a molecular weight of 926 - 940 g/mol, and a slight water solubility of 3.93 mg/L. As the substance was an inorganic, no partition coefficient (log Pow / Kow) could be determined. In addition, the reaction mass displayed a pH ranging from 6.3 to 6.6 and no particular reactivity in terms of exothermic or oxidizing reactions. Thus, based on the physico-chemical characteristics of the substance and according to the OECD guidance document on an IATA for skin corrosion and irritation (2014), it was hypothesised that the reaction mass of neodymium carbonate and praseodymium carbonate had no corrosive or irritant potential to the skin. The physico-chemical characteristics of both constituents, dineodymium tricarbonate and dipraseodymium tricarbonate, were similar to the ones of the reaction mass: a melting point > 300°C, a molecular weight around 460 g/mol, a water solubility of 4.39 mg/L at most, a pH ranging from 6.0 to 6.4, no partition coefficient and no specific reactivity in terms of exothermic or oxidizing reactions. These data thus suggested that, as the reaction mass, its constituents had no corrosive or irritant potential to the skin. Moreover, the physico-chemical data on 3 analogues (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide) also suggested that there was no alert regarding the skin corrosive / irritant potential of these 3 analogous substances.  

 

As a skin corrosion study was available on dineodymium tricarbonate, the major constituent of the reaction mass (~79%), which showed similar physico-chemical and toxicological properties, no corrosion study was performed on the reaction mass of neodymium carbonate and praseodymium carbonate. The data on the constituent were used in a read-across approach to conclude on the skin corrosion potential of the reaction mass of neodymium carbonate and praseodymium carbonate. This read-across approach allowed preventing unnecessary animal testing, as recommended by REACh.

 

The skin corrosivity potential of dineodymium tricarbonate was tested in vitro using the Episkin^TM reconstituted human epidermis model, according to OECD guideline 431 and in compliance with GLP (Warren N., 2010a). This study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and was flagged as supporting study. Duplicate tissues were exposed to the test item (20 mg in 2.2-mL solution) for 3, 60 and 240 min. At the end of exposure, viability was assessed based on the MTT reduction in the test material treated tissues relative to the negative control tissues. The relative mean viability of the test material treated materials was 100.4%, 107.4%, and 91.4% after 240, 60, and 3 min, respectively. Thus, the test material was considered to be non-corrosive to the skin. 

 

The skin irritation potential of the reaction mass of neodymium carbonate and praseodymium carbonate was tested  in vitro. Conducted in compliance with GLP and according to the OECD guideline 439 (Episkin), this study was awarded a reliability 1 according to Klimisch quotation criteria and was flagged as key study (Valin M., 2013). The reaction mass was topically applied in its original form (i.e. solid) at a quantity of 10 ± 2 mg on triplicate tissues (Episkin^TM reconstituted human epidermis model) for 15 ± 1 min followed by a 42-h (± 1 h) recovery period in fresh medium. Following the 15-min exposure and 42-h recovery period, the relative mean viability of the tissues treated with the test substance was 107% with a standard deviation of 12%. Thus, as the mean viability was > 50% in tissues exposed to the reaction mass of neodymium carbonate and praseodymium carbonate, the test substance was considered to be non-irritant to the skin.

 

Moreover, data on skin irritation potential of one constituent and three analogues were available and thus used in a weight-of-evidence approach to conclude on the skin irritating property of the reaction mass of neodymium carbonate and praseodymium carbonate.  

First, an in vitro skin irritation study was available on dineodymium tricarbonate, the main constituent of the reaction mass (Warren N., 2010b). In this study (OECD Guideline 439, GLP), scored as Klimisch 2 due to read-across and flagged as weight of evidence, the skin irritation potential of the test material was evaluated using the Episkin^TM  reconstituted human epidermis model after a treatment period of 15 min followed by a post-exposure incubation period of 42 h. Skin irritation was determined from the measurement of cytotoxicity in triplicate tissue cultures following topical exposure to the test material (10 mg in 2-mL solution) by means of the colourimetric MTT reduction assay. The quality criteria required for acceptance of results in the test were satisfied. The relative mean viability of the test material treated tissues was 96.1% after a 15-min exposure. Thus, dineodymium tricarbonate was considered to be non-irritant to the skin.

 

Further, in vivo  studies on three analogues were available: dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide. Performed on dicerium tricarbonate, according to standardised guidelines, the first study was a short summary in which the information necessary for the assessment were given (Lambert C.E. et al.,1993a). The publication was scored as Klimisch 2 and flagged as weight of evidence. In this study, 6 New Zealand Albino rabbits were dermally exposed to 0.5 g of dicerium tricarbonate for 24 h to ca. 2.5 cm² of one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 h. Animals were then observed for 3 days. Irritation was scored by the method of Draize. As no signs of dermal irritation were observed and the primary dermal irritation index (PDII) was of 0 (mean), dicerium tricarbonate was considered as non-irritant to the skin.

The second in vivo study was conducted with neodymium oxide, according to OECD guideline 404 (Guillot J.P.,1984a).This study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and was flagged as weight of evidence. In this dermal irritation study, albino New-Zealand rabbits (6 males) were dermally exposed to 0.5 mL of neodymium oxide applied as such, as a paste with 0.16 mL of water on 6 cm² body surface area. Test sites were covered with a semi-occlusive dressing for 4 h. Animals were then observed for 14 days. Irritation was scored based on erythema and edema observed 1, 24, 48 and 72 h after the end of application. No skin reactions were observed during the study. The mean score for the reading times 24, 48 and 72 hours of the 6 rabbits for both erythema and edema was equal to 0. Therefore, in this study, neodymium oxide was considered as non-irritant to the skin.

At last, a primary dermal irritation study was available on praseodymium(III,IV) oxide (Lambert C.E. et al.,1993b).Performed according to standardised guidelines, this brief summary, in which the most important information were given, was scored as Klimisch 2 and flagged as weight of evidence.As described above for dicerium tricarbonate, 6 New Zealand Albino rabbits were dermally exposed to 0.5 g of praseodymium(III,IV) oxide for 24 h to ca. 2.5 cm² of one intact and one abraded skin site. Test sites were covered with an occlusive dressing for 24 h. Animals were then observed for 3 days. Irritation was scored by the method of Draize. As no signs of dermal irritation were observed and the PDII was of 0 (mean), praseodymium(III,IV) oxide was considered as non-irritant to the skin.

 

As the main constituent of the reaction mass, dineodymium tricarbonate (~79%), showed no evidence of skin corrosion or skin irritation in vitro, the reaction mass of neodymium carbonate and praseodymium carbonate is expected to be non-corrosive and non-irritant to the skin. This hypothesis is consistent with the results of the in vitro skin irritation study carried out on the reaction mass itself. Indeed, the test substance was found to be non-irritant to the skin model used in this study. Furthermore, the absence of skin corrosion / irritation potential of the reaction mass is further corroborated by the data on the three analogues (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide) all showing no skin irritation in vivo. Based on the study performed with the reaction mass itself and as the reaction mass of neodymium carbonate and praseodymium carbonate showed similar physico-chemical and toxicological properties compared to the abovementioned constituent and analogues, the reaction mass is considered to be non-corrosive and non-irritant to skin, therefore warranting no classification for skin irritation / corrosion according to the criteria of Annex VI of Directive 67/548/EEC, Regulation (EC) No. 1272/2008 and UN GHS. 

 

Eye irritation

 

There was no eye irritation study available on the reaction mass of neodymium carbonate and praseodymium carbonate. However, seven studies were available on both reaction mass constituents (in vitro and in vivo) as well as on analogues (in vivo) all showing similar physico-chemical and toxicological properties (i.e. dineodymium tricarbonate, dipraseodymium carbonate, dicerium tricarbonate, neodymium oxide and praseodymium(III,IV) oxide). Thus, data on constituents and analogues were used in a weight-of-evidence approach to conclude on the eye irritation potential of the reaction mass of neodymium carbonate and praseodymium carbonate.

 

The first in vitro eye irritation study available was performed on dineodymium tricarbonate (Warren N., 2010c), the major constituent of the reaction mass (~79%). Although there was no data regarding the guideline, this study was performed in compliance with generally acceptable scientific principles; thus, it was awarded a reliability 2 (Klimisch, 1997) and was flagged as weight of evidence. The eye irritation potential of dineodymium tricarbonate was determined using the SkinEthic Reconstituted Human Corneal model. Triplicate tissues were exposed to the test item (30 mg) for 10 minutes. At the end of exposure, viability was assessed based on the MTT reduction in the test material treated tissues relative to the negative control tissues. The relative mean viability of the test material treated tissues after a 10 minute exposure was 105.2%, well above the criteria set to be considered an irritant (relative mean tissue viability was ≥ 60%). Thus, dineodymium tricarbonate was considered to be non-irritant to the eyes. 

 

A second in vitro eye irritation study was available on dipraseodymium tricarbonate (Warren N., 2013), the minor constituent of the reaction mass (~21%). Performed according to standardised guidelines and in compliance with GLP, this study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and flagged as weight of evidence. The eye irritation potential of dineodymium tricarbonate was determined using the SkinEthic Reconstituted Human Corneal model. Triplicate tissues were exposed to the test item (30 mg) for 10 minutes. At the end of exposure, viability was assessed based on the MTT reduction in the test material treated tissues relative to the negative control tissues. The relative mean viability of the test material treated tissues after a 10 minute exposure period was 77.6 %, well above the criteria set to be considered an irritant (relative mean tissue viability was ≥ 60%). Thus, dipraseodymium tricarbonate was considered to be non-irritant to the eyes. 

 

Then, in vivo studies conducted on both constituents of the reaction mass and three analogues were available (i.e. dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide). 

The first in vivo eye irritation study available was performed on dineodymium tricarbonate (Sanders A., 2010b), the major constituent of the reaction mass. Performed according to OECD guideline 405 and in compliance with GLP, the study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and flagged as weight of evidence. In this eye irritation study, 2 male New-Zealand White rabbits were observed for up to 3 days following a single conjunctival instillation of dineodymium tricarbonate (69 mg in 0.1 mL) in unwashed eyes. Signs of mild ocular irritation were noted, mainly 1 h after instillation: the mean scores were of 0, 0, 0.67 and 0.67 for cornea, iris, conjunctivae and chemosis, respectively. All signs were fully reversible within 72 h. These observations were consistent with the other  in vivo  study (Sanders A., 2013) performed on the minor constituent of the reaction mass, dipraseodymium tricarbonate. Performed according to OECD guideline 405 and in compliance with GLP, the study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and flagged as weight of evidence. As described above for dineodymium tricarbonate, 2 New-Zealand rabbits were observed for up to 3 days following a single conjunctival instillation of dipraseodymium tricarbonate (86 mg in 0.1 mL) in unwashed eyes. Mild signs of conjunctival redness and chemosis were noted, mainly 1 h after instillation: the mean scores were of 0, 0, 0.33 and 0.33 for cornea, iris, conjunctivae and chemosis, respectively. These signs were fully reversible within 48 h. Thus, dineodymium tricarbonate and dipraseodymium tricarbonate were considered to be non-irritant in vivo to the rabbit eyes. 

 

Further, three other in vivo studies on analogues were available: dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide. Performed on dicerium tricarbonate, according to standardised guidelines, the first study was a short summary in which the information necessary for the assessment were given (Lambert C.E. et al., 1993a). The publication was scored as Klimisch 2 and flagged as weight of evidence. In this primary eye irritation study, 6 New Zealand Albino rabbits were instilled with 0.1 g of dicerium tricarbonate in the left eye and 3 treated eyes were rinsed after 30 seconds. Animals then were observed for 3 days. Irritation was scored by the method of Draize. Dicerium tricarbonate was found slightly irritating to both washed and unwashed rabbit eyes: the Draize scores for irritation ranged between 0.7 and 6.8 for unwashed eyes (mean score = 3.1), between 1.3 and 4.7 for washed eyes (mean score = 2.7). Effects were not fully reversible during the observation period (up to 72 h). However, considering the observed decrease in scores during the 24- to 72-h period, the full reversibility could have occurred during the 21-day period following instillation. Based on the low intensity and short duration of the findings, dicerium tricarbonate was considered to be non-irritant to the eyes.

The second in vivo study was conducted with neodymium oxide, according to OECD guideline 405 (Guillot J.P.,1984b).This study was awarded a reliability 2 (Klimisch, 1997), since used as read-across, and was flagged as weight of evidence. In this eye irritation study, 0.1 g of neodymium oxide was instilled into the conjunctival sac of the right eye of 6 male Albino New-Zealand rabbits, without rinsing. Animals were then observed for 21 days. Ocular irritation was scored based on changes on iris, cornea, conjunctivae and chemosis at 24, 48 and 72 h. The mean scores of the 6 rabbits were 0 for corneal opacity, 0.11 for iritis, 0 for redness and 0 for chemosis of the conjunctivae. Thus,neodymium oxide was considered to be non-irritant to the eyes.

At last, an eye irritation study was available on praseodymium(III,IV) oxide  (Lambert C.E. et al.,1993b).Performed according to standardised guidelines, this brief summary, in which the most important information were given, was scored as Klimisch 2 and flagged as weight of evidence. As described above for dicerium tricarbonate, 6 New Zealand Albino rabbits were instilled with 0.1 g of praseodymium(III,IV) oxide into the left eye and 3 treated eyes were rinsed after 30 seconds. Animals then were observed for 3 days. Praseodymium(III,IV) oxide was found slightly irritating to both washed and unwashed rabbit eyes: the Draize scores for irritation ranged between 0.7 and 13 for unwashed eyes (mean score = 5.8), between 0 and 9 for washed eyes (mean score = 3.7). Effects were fully reversible during the observation period (up to 72 h) only for washed eyes. Considering the observed decrease in scores during the 24- to 72-h period, the full reversibility for unwashed eyes could have occurred during the 21-day period following instillation. Based on the low intensity and short duration of the findings, praseodymium(III,IV) oxide was considered to be non-irritant to the eyes.

 

As both constituents of the reaction mass, dineodymium tricarbonate and dipraseodymium tricarbonate, showed no evidence of eye irritation in vitro and in vivo the reaction mass of neodymium carbonate and praseodymium carbonate is expected to be non-irritant to the eye. This hypothesis is further supported by the results of the in vivo eye irritation studies carried out on three analogues (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide), all showing no eye irritation in vivo. Altogether, these results indicated that the reaction mass of neodymium carbonate and praseodymium carbonate should be considered non-irritant to the eye, therefore warranting no classification for eye irritation according to the criteria of Annex VI of Directive 67/548/EEC, Regulation (EC) No. 1272/2008 and UN GHS.

 

Skin and Eye irritation / corrosion	Reaction mass of neodymium carbonate and praseodymium carbonate	Dineodymium tricarbonate	Dipraseodymium tricarbonate	Dicerium tricarbonate	Neodymium oxide	Praseodymium(III,IV) oxide
Skin irritation / corrosion	not irritating in vitro	not corrosive in vitro not irritating in vitro	no data	not irritating  in vivo	not irritating  in vivo	not irritating  in vivo
Eye irritation / corrosion	no data	not irritating in vitro not irritating in vivo	not irritating in vitro not irritating in vivo	slightly irritating but not classified in vivo	not irritating  in vivo	slightly irritating but not classified in vivo

 

Respiratory irritation

 

There was no respiratory irritation study available on either the reaction mass of neodymium carbonate and praseodymium carbonate, or its constituents or analogous substances. However, such effect was not expected as the tested substances showed no skin/eye irritation potential and, furthermore, no irritation-like injury were observed in the acute oral/inhalation studies performed on the reaction mass.

Justification for selection of skin irritation / corrosion endpoint:
Several studies done on the reaction mass of neodymium carbonate and praseodymium carbonate as well as on one constituent (dineodymium tricarbonate) and three analogues (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide) of the reaction mass were selected. The reaction mass was found non-irritant in an in vitro study performed according to the OECD guideline 439 and in compliance with GLP; thus, the study was awarded a reliability score of 1 according to Klimisch scale and was considered as the key study. This result was supported by 2 in vitro studies conducted in compliance with GLP and according to the OECD guidelines 431 and 439 in which dineodymium tricarbonate (the major constituent of the reaction mass, at ~79%) was found to be non-corrosive and non-irritant to the skin. Both studies on dineodymium tricarbonate were considered in a read-across approach to help in the conclusion on the skin irritation / corrosion potential of the reaction mass of neodymium carbonate and praseodymium carbonate. Although the reports on the main constituent of the reaction mass were well described, the data were used as read-across and therefore the maximal reliability score was decreased from 1 to 2 (Klimisch, 1997), according to Practical Guide n°6. The studies were flagged as supporting study (skin corrosivity study) and weight of evidence (skin irritation study).

All performed in vivo according to OECD or standardised guidelines, 3 other studies on analogues (dicerium tricarbonate, neodymium oxide and praseodymium(III,IV) oxide) showing no in vivo skin irritation potential were also considered in this read-across approach. The studies were thus flagged as weight of evidence. As the data were used as read-across, the maximal reliability score was therefore decreased from 1 to 2 (Klimisch, 1997), according to Practical Guide n°6.
This read-across approach was chosen as it allowed preventing unnecessary animal testing, as recommended by REACh.

Justification for selection of eye irritation endpoint:
No study is available on the reaction mass of neodymium carbonate and praseodymium carbonate. However as several studies done on both constituents of the reaction mass (i.e. dineodymium tricarbonate and dipraseodymium tricarbonate), as well as on three analogues (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide) of the reaction mass were available, all of them were used in a weight of evidence approach to conclude on the eye irritant potential effect of the reaction mass. Performed on both constituents of the reaction mass showing similar physico-chemical and toxicological properties, in vitro and in vivo eye irritation studies were conducted in compliance with GLP and according to standardised guidelines (i.e. SkinEthic and OECD 405). The 4 studies concluded to non-irritant effects to the eyes of the constituents of the reaction mass. Although the in vitro and in vivo studies on the two constituents were well described, the data were used as read-across and therefore the maximal reliability score was decreased from 1 to 2 (Klimisch, 1997), according to Practical Guide n°6. The studies were flagged as weight of evidence.

All performed in vivo according to OECD or standardised guidelines, 3 other studies on analogues (dicerium tricarbonate, neodymium oxide and praseodymium(III,IV) oxide) showing no eye irritation potential were also considered in this weight-of-evidence approach.. As the data were used as read-across, the maximal reliability score was therefore decreased from 1 to 2 (Klimisch, 1997), according to Practical Guide n°6.

This read-across approach was chosen as it allowed preventing unnecessary animal testing, as recommended by REACh.

Justification for classification or non-classification

The available data on the reaction mass of neodymium carbonate and praseodymium carbonate, on the constituents (dineodymium tricarbonate, dipraseodymium tricarbonate, ) and on constituent analogous (dicerium tricarbonate, neodymium oxide, praseodymium(III,IV) oxide) show that irritation / corrosion to either skin or eyes does not occur after exposure to the test items. Thus, the reaction mass of neodymium carbonate and praseodymium carbonate is not classified as skin, eye, or respiratory irritant according to Annex VI of Directive 67/548/EEC, Regulation (EC) No. 1272/2008 and UN GHS classification criteria.