Dichromium nitride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Justification for type of information:

Skin penetration experiments on chromium chloride and chromium sulfate (1.2% chromium labelled with 51Cr) with skin chambers glued to the skin of normal volunteers. These chambers were removed at 6, 12, or 24 hours and analysis for radioactive chromium was performed at the site of the chamber as well as in the underlying epidermis and dermis. As no label was found in the lower levels of skin, it was concluded that chromium(III) salts did not permeate through the intact epidermis.
References:
Mali JWH, Van Kooten WJ, Van Neer CJ (1963) Some aspects of the behaviour of chromium compounds in the skin. Journal of Investigative Dermatology, 41:111–122.

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

transformation/dissolution in artificial physiological media

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Objective of study:

bioaccessibility (or bioavailability)

Qualifier:

no guideline available

Version / remarks:

There is not an internationally agreed guideline for these tests (e.g. OECD). However, similar tests have been conducted for several metal compounds incl. steels in previous EU risk assessments.

Principles of method if other than guideline:

The aim of these tests is to assess the dissolution of chemical compounds in a set of artificial physiological media. The test media are selected to simulate relevant human-chemical interactions (as far as practical), i.e. contact of a test substance with skin, a substance entering the human body by inhalation or by ingestion into the gastro-intestinal tract. Principle of test is similar to OECD Series on testing and assessment number 29 guidance document on transformation/dissolution of metals and metal compounds in aqueous media (2001; document ENV/JM/MONO(2001)9). The dissolved amount of the test item was specified by measured dissolved Cr concentrations in the test media under the applied test conditions.

GLP compliance:

no

Specific details on test material used for the study:

Cr-N powder sized less than 40 µm. The surface area of the Cr-N powder was 0.61m2/g, and the particles displayed the presence of several large chiselled boulder-like particles, typically sized 20–30 μm, to which smaller-sized particles (5 μm) adhered to a large extent. In addition, a significant amount of smaller-sized particles (<10 μm), all with sharp edges, were present within the powder.

Species:

other: in vitro (simulated human body fluids)

Duration and frequency of treatment / exposure:

Samples were taken after 2, 4, 8, 24 and 168 h.

Dose / conc.:

100 other: mg of test item/L artificila media

Type:

other: Bioacessibility

Results:

Dissolution of Cr after 168 h at a loading of 100 mg/L in PBS: ≤ 0.0028%, GMB:≤ 0.0027%, ALF: ≤ 0.0142%, GST: ≤ 0.0143%, ASW: ≤ 0.0071 %

Mean released concentrations and standard deviations (SD) in µg/L of chromium for Cr2N particles after exposure in the different biological fluids (GST-gastric fluid, ALF - artificial lysosomal fluid, ASW - artificial sweat, GMB - Gamble's solution, PBS - phosphate buffered saline). Values corrected for Cr background.

	GST		ALF		ASW		PBS		GMB
h	Mean	SD	Mean	SD	Mean	SD	Mean	SD	Mean	SD
2	5,5	0,8	2,0	0,9	1,6	0,7	4,4	1,1	0,9	0,7
4	4,8	1,1	3,2	0,2	2,7	1,6	2,8	0,4	<LOQ	<LOQ
8	5,7	0,4	4,2	0,4	2,4	1,1	4,7	2,3	1,7	0,5
24	8,6	1,5	8,2	0,5	4,5	1,4	9,4	6,1	1,8	0,7
168	14,3	0,9	14,2	0,4	7,1	1,3	2,8	0,1	2,7	0,2

Mean released chromium per particle surface area (µg/m2) for CrN particles after exposure in the different biological fluids. (GST-gastric fluid, ALF - artificial lysosomal fluid, ASW - artificial sweat, GMB - Gamble's solution, PBS - phosphate buffered saline). Values corrected for Cr background.

h	GST	ALF	ASW	PBS	GMB
2	89,6	33,3	25,4	71,5	14,9
4	78,2	51,9	43,6	45,8	< LOQ
8	93,1	69,5	39,2	76,8	27,7
24	141,7	133,6	74,3	154,2	29,2
168	235,2	232,1	116,4	46,3	43,6

Remarks on data treatment:

Concentrations below the LOD are estimated according to: LOD/√2

Concentrations below the LOQ are estimated according to: LOD+0.5(LOQ-LOD)

Measured dissolved Cr concentrations in method blanks:

h	GST pH 1.7	ALF pH 4.5	ASW pH 6.5	PBS pH 7.2	GMB pH 7.4
2	< LOD	2,66	1,69	0,77	1,23
4	< LOD	2,49	1,41	0,64	< LOD
8	0,54	2,50	1,64	0,66	< LOD
24	< LOD	2,39	1,31	0,73	< LOD
168	0,50	2,74	1,49	0,62	< LOD

Conclusions:

The bioaccessibility of chromium nitride powder (< 40 µm, BET specific surface area 0.61 m2/g) has been investigated in vitro by simulating dissolution under physiological conditions considered to mimic the most relevant exposure routes (oral, dermal and inhalation). After 168 h (loading: 100 mg/L), dissolved chromium concentration in five artificial body fluids, i.e. phosphate-buffered saline (PBS), Gamble’s solution (GMB), lysosomal fluid (ALF), gastric fluid (GST), sweat (ASW), were ≤ 0.0028, ≤ 0.0027, ≤ 0.0142, ≤ 0.0143, and ≤ 0.0071 %, respectively. Based on a solubility of less than 0.015 % in all five artificial body fluids, chromium nitride powder may reasonably be considered biologically inert.