Chromium

Endpoint summary

Description of key information

In vitro release studies with Cr metal, FeCr, FeSiCr and Cr2O3 show that the release rate of Cr into different artificial body fluids is very low, and therefore the bioaccessibility is also low. Few studies were available on the toxicokinetics of chromium metal. Therefore, available studies with chromium  (III) oxide and other chromium(III) salts have been used in this dossier. The surface of chromium is always covered by chromium (III) oxide and therefore study results with this substance can readily be compared to chromium. Other chromium (III) salts are more soluble than chromium metal, but it can be assumed that the kinetic behavior is quite similar to chromium.

In another bioaccessibility test (Knopf, 2020) in three different surrogate lung fluids (GMB, ALF, HTC) with a loading of 2 g/L, dichromium trioxide was similarly poorly soluble (< 0.005% of loading): after 168h a maximum of total dissolved chromium (3kDa filtered to be particle-free) was measured to be 19.6 µg/L, 61.3µg/L and 0.55µg/L in GMB, ALF and HTC respectively. In all three media, Cr (III) concentrations were measured to be close to or below the LOD. Based on the known complexation behavior of trivalent chromium, it can be hypothesized that dissolved Cr (III) formed complexes with e.g. anions such as acetate or citrate, or also with proteins such as BSA or Lysozyme (as contained in the media) and was thus observed in the chromatograms as “Cr Complex”. The highest Cr (VI) concentration of 21.6 µg/L was measured after 24 h in GMB and can without doubt be attributed to the analytically verified very minor Cr VI impurity of dichromium trioxide (< 0.01 %). Thus, the rate and extent to which chromium (III) oxide produces soluble (bio)available ionic and other chromium-bearing species is extremely limited.

Absorption of chromium in the body is largely dependent on chromium species. Intratracheal studies on chromium (III) oxide and chromite show that lung clearance of these insoluble chromium compounds is slow. The elimination half-life was 11 days in sheep administered chromium (III) oxide and 6 months in rats after intratracheal administration of chromite particles. No studies on gastrointestinal absorption is available on poorly soluble chromium (III)) species, but even soluble chromium (III)chloride is absorbed only at the levels of <2% from the GI-tract . Thus, the oral absorption of chromium metal is likely to be very low, due to the practically insoluble nature of the substance. The dermal absorption of chromium metal has been tested by in vitro models, and has been shown to be very low.

 

Most studies of absorption of Cr III or Cr VI even conducted on more soluble form of chromium III (Chromium chloride) after oral administration to rodents find that only 1% or 2% of the administered dose is bioavailable, whereas similar studies with humans report somewhat higher numbers (Donaldson, 1966 ; Sayato, 1980, ATSDR, 2000).

The toxicokinetic on chromium has also been discussed and summarized in several reports, including the NTP study on chromium picolinate (Stout ; 2010) and as follows:

“Ingested chromium is excreted primarily in the feces because of its poor absorption. Absorbed chromium is primarily excreted in the urine (Donaldson and Barreras, 1966; Sayato et al., 1980). The distribution studies of Hepburn and Vincent (2002, 2003) revealed that most of the 51Cr was excreted in urine in the first 12 hours after

dosing. However, the loss was only about 10% of the administered dose.”

 

In the blood plasma most of the chromium is bound to large molecular mass proteins (e. g. transferrin). Chromium associates also with the oligopeptide low-molecular-weight chromium-binding substance (chromodulin). In blood, chromium is mostly (about 95%) bound to large molecular weight plasma proteins and only a minor part of the chromium can be found in erythrocytes.

 

The administered Cr is mainly distributed into the liver, kidneys, spleen and bone. Some Cr may also reach the interstitium of the testis, and it may accumulate in the placenta. Only low amounts have been shown to cross the placenta. Many of these toxicokinetic studies were done with CrCl3, which is much more soluble than chromium metal. Therefore, the absorption of this substance is much higher than that of the practically insoluble chromium metal and the systemic distribution of chromium is likely to be significantly lower.

 

The excretion of absorbed chromium (III) occurs mainly in the faeces, and to a low extent in the urine.

 

The existing toxicokinetic studies show that trivalent chromium (in contrast to hexavalent chromium) is poorly absorbed. Less than 1% of chromium III is absorbed from the normal diet, inhaled chromium III uptake is a very slow process, and chromium III compounds were not shown to be absorbed across the skin into systemic circulation (ATSDR, 2000 ; NTP, 2010). The prominent tissues of chromium distribution are the liver, kidneys and spleen as well as bone and the remaining carcass (muscle, skin and hair). There is no clear evidence to show the valency of trivalent chromium changes during metabolism and chromium III is mainly excreted in the urine and to a lesser extent in the faeces.

Key value for chemical safety assessment

Absorption rate - dermal (%):

1