Diammonium sodium hexakis(nitrito-N)rhodate

Endpoint summary

Description of key information

Diammonium sodium hexakis(nitrito-N)rhodate is likely to be appreciably absorbed and rapidly excreted after administration by the oral route, based on limited experimental insights and extensive bio-elution in simulated gastric fluid. As such, predicted oral absorption is set at 100%.

 

Although exposure by the inhalation route is anticipated to be low, based on limited experimental data inhalation absorption is potentially extensive. In line with ECHA guidance, a conservative assumption of 100% inhalation absorption is proposed.

 

Significant bioavailability after dermal exposure is unlikely, given the low dermal penetration expected for metals and the observed lack of skin irritation potential. A value of 10% dermal absorption is proposed.

 

Once absorbed, distribution and excretion are expected to be rapid, with little or no bioaccumulation anticipated. The potential for bioaccumulation of certain other metals and ions is recognised.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

Absorption

No good-quality information on oral absorption of rhodium compounds was identified. One report noted that organic salts of rhodium “can be absorbed by the gastro-intestinal tract”, but quantitative absorption data were not given (Iavicoli et al., 2013). In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. Based on expert ECHA guidance, the relatively low molecular weight (~440 g/mol) and, more critically, the moderate water solubility (0.76 g/L; Gregory, 2014) are indicative of a high bioavailability of diammonium sodium hexakis(nitrito-N)rhodate, as ions, by this route. Furthermore, in a bio-elution test the proportion of metal release (from total metal content) in simulated gastric fluid was extensive (115%) after 2 hours (Rodriguez, 2012). A health-precautionary assumption is that the ions will be absorbed from the gastro-intestinal tract. As such, predicted oral absorption of diammonium sodium hexakis(nitrito-N)rhodate is set at 100%.

 

No good-quality data were found regarding absorption of rhodium compounds following inhalation. One report noted that organic salts of rhodium may be absorbed via inhalation following occupational exposure, but quantitative absorption data were not given (Iavicoli et al., 2013). Particle size distribution (PSD) data, as measured by simple sieving, indicate that only a small proportion (0.696%) of diammonium sodium hexakis(nitrito-N)rhodate is <100 μm (Tremain and Atwal, 2011). Dustiness testing, a more energetic PSD measurement, with the compound returned a mass median aerodynamic diameter (MMAD) value of 29.0 μm (Parr, 2011; Selck and Parr, 2011). An MMAD value <100 μm indicates that a significant proportion of the substance is likely to be inhalable. However, respiratory tract deposition modelling with the dustiness data yielded output values of 47.6, 0.20 and 0.32% for the nasopharyngeal (head), tracheobronchial (TB) and pulmonary regions of the respiratory tract, respectively. This indicates that little airborne substance (<1%) will be deposited in the lower regions of the human respiratory tract, i.e. the TB or pulmonary regions via oronasal normal augmenter breathing.

 

Most of the inhaled fraction is likely to be retained in the head region and therefore would be cleared by ingestion, along with that deposited in the TB region, and oral bioavailability will again predominantly determine systemic uptake. Only 0.32% is likely capable of reaching the alveoli. Thus, inhalation will not be a significant route of exposure. However, as a moderately water soluble substance, any diammonium sodium hexakis(nitrito-N)rhodate reaching the lungs is likely to be absorbed through aqueous pores or be retained in the mucus and transported out of the respiratory tract.

 

While it is very unlikely that diammonium sodium hexakis(nitrito-N)rhodate will be available to a high extent via the lungs, ECHA guidance notes that “if data on the starting route (oral) are available these should be used, but for the end route (inhalation), the worst case inhalation absorption should still be assumed (i.e. 100%)”. Therefore, the health-precautionary figure of 100% as recommended by ECHA has been taken forward.

 

No good-quality data were found regarding absorption following dermal exposure to rhodium compounds. The moderate water solubility suggests that diammonium sodium hexakis(nitrito-N)rhodate may be able to cross the lipid-rich environment of the stratum corneum to a “moderate to high” extent, indicating that the appropriate default value for dermal absorption is 100% in this case (ECHA, 2014). However, specific expert guidance on the health risk assessment of metals states that “inorganic compounds require dissolution involving dissociation to metal cations prior to being able to penetrate skin by diffusive mechanisms” and, as such, dermal absorption might be assumed to be very low (values of 0.1 and 1.0% are suggested for dry and wet media, respectively) (ICMM, 2007). Furthermore, there is no evidence that the substance causes skin irritation (which could facilitate a greater degree of dermal uptake) (Kiss, 2012a). In bio-elution tests with diammonium sodium hexakis(nitrito-N)rhodate, the proportion of metal release (from total metal content) in simulated dermal fluid was 15.95% and 38.4% after 24 and 168 hours, respectively (Rodriguez, 2012). Overall, it is suitably health precautionary to take forward the lower of the two ECHA default values for dermal absorption, of 10%.

 

Distribution/Metabolism

Once absorbed, distribution of ammonium/sodium and hexakis(nitrito-N)rhodate ions throughout the body is expected based on a relatively low molecular weight (~440 g/mol).

 

A combined repeated dose and reproductive/developmental toxicity dietary study in rats on diammonium sodium hexakis(nitrito-N)rhodate found changes in the lungs, kidney, pancreas and thymus (Török-Bathó, 2015), suggesting possible distribution to these organs.

 

Elimination (and Bioaccumulation)

In rats treated orally with Rhodium trichloride for 14 days, absorbed rhodium was mainly excreted through the urinary system (Iavicoli et al., 2013).

 

It is noted that certain metals and ions may interact with the matrix of the bone, causing them to accumulate within the body (ECHA, 2014). However, diammonium sodium hexakis(nitrito-N)rhodate is considered to have only a low potential for bioaccumulation based on its predicted physico-chemical properties (i.e. water solubility of 0.76 g/L).

 

Conclusion

Based on the physico-chemical properties, the chemical structure, molecular weight and the results of toxicity studies, as well as limited insights on organic rhodium salts, it can be assumed that diammonium sodium hexakis(nitrito-N)rhodate is likely partially bioavailable by the oral route and rapidly excreted once absorbed. Although inhalation is not anticipated to be a significant route of exposure (based on respiratory tract deposition modelling data), absorption could be extensive. A high dermal bioavailability is unlikely.

 

Absorption values of 100%, 10% and 100% are proposed for the oral, dermal and inhalation routes, respectively, and are considered health-precautionary for use in the calculation of DNEL values.

 

 

References (for which an ESR has not been created in IUCLID):

ECHA (2014). European Chemicals Agency. Guidance on information requirements and chemical safety assessment. Chapter R.7c: endpoint specific guidance. Version 2.0. November 2014.

 

Iavicoli I, Leso V, Fontana L, Marinaccio A, Bergamaschi A and Calabrese EJ (2013). The effects of rhodium on the renal function of female Wistar rats. Chemosphere (article in press).

 

ICMM (2007). International Council on Mining & Metals. Health risk assessment guidance for metals. September 2007.