Chromium trichloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

Variable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A review of proprietary studies reported in summary form.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

review article or handbook

Title:

Health Risk Assessment Report for Metallic Chromium and Trivalent Chromium

Author:

International Chromium Development Association

Year:

2006

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

Various protocols, dose levels and routes of administration were used in the studies reviewed.

GLP compliance:

not specified

Remarks:

: published studies assumed not to be GLP-compliant

Test material

Test material information

Constituent 1

Reference substance name:

Chromium hydroxide sulphate

EC Number:

235-595-8

EC Name:

Chromium hydroxide sulphate

Cas Number:

12336-95-7

Constituent 2

Reference substance name:

Chromium (III) compounds

IUPAC Name:

Chromium (III) compounds

Test material form:

other: various

Details on test material:

Various water-soluble chromium (III) compounds were used as the test material.

Radiolabelling:

other: in some studies

Test animals

Species:

other: various

Strain:

other: various

Sex:

male/female

Administration / exposure

Route of administration:

other: various routes of administration were used in the studies reviewed.

Vehicle:

not specified

Duration and frequency of treatment / exposure:

Various treatment protocols were used

Doses / concentrations

Remarks:

Doses / Concentrations:
Various dose levels were used in the studies reviewed.

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

See details below

Details on distribution in tissues:

See details below

Details on excretion:

See details below

Metabolite characterisation studies

Metabolites identified:

no

Details on metabolites:

Cr (III) is not metabolised. The data indicate that there is no conversion to other forms of Cr in the body.

Any other information on results incl. tables

Absorption

Oral studies conducted in male and female rats using radiolabeled water-soluble chromium (III) showed that the bioavailability of chromium chloride over a wide dose range was low (about 1%). Intestinal absorption of water-soluble chromium (III) chloride given orally to volunteers was low ranging from non-detectable to about 4%. It should be noted that occupational exposure to airborne dusts/aerosols of chromium (III) compounds is variably transformed to oral intake due to muciliary clearance of the substance from the respiratory system. No increases in chromium levels were detected in blood and urine samples taken over a 24 hour period after a male research volunteer held his hand in a tanning solution containing 7 g/L chromium as basic chromium sulphate for one hour. Rats were exposed to aerosols of the water soluble chromium (III) compound, chromium chloride hexahydrate, for 2 hours at 10.7 mg/m3 or for 6 hours at 8 mg/m3. Chromium concentrations in the lungs and other tissues were highest at 0.5 h post exposure. This indicates that a fraction of the deposited chromium had been absorbed rapidly, and the remaining lung chromium was cleared more slowly.

Distribution

Retention of radiolabeled chromium chloride was less than 1% of the dose two days after oral administration to male and female rats and 0.3% on day 20.

Tanners on retirement (exposure was mainly to basic chromium sulphate) for at least 15 months exhibited normal chromium levels in serum, urine and hair, demonstrating that markedly increased long-term body burdens of chromium had not developed.

In rats exposed to aerosols of chromium chloride hexahydrate, lung chromium concentrations at 0.5 hours post exposure were nearly proportional to the product of exposure concentration and time. Radiolabelled chromium chloride in different tissues was measured 24-h after intratracheal instillation in rats. About 5% of the dose was recovered in lung lavage, 23% was still contained in the lungs and trachea. The highest tissue levels were found in the kidney, femur, large intestine and blood.

Excretion

After the first 6 days, the elimination of radiolabeled chromium chloride in the rat followed a half-time of about 92 days. Over 20 post-administration days, 99% of the oral dose was excreted in faeces and 0.8% in the urine. Regarding exposures to soluble basic chromium sulphate among tanners, chromium in serum decreased by more than 50% over 9 months post exposure and, in another study with a follow-up of 40 days, chromium decreased in urine with an apparant half-time of about one month. Concentrations of chromium chloride hexahydrate in rats exposed to water soluble chromium (III) aerosols declined monoexponentially with an elimination half-time of 6.8 days.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
This review supports the conclusion that trivalent chromium compounds have low systemic availability by all routes of exposure.

Executive summary:

Absorption is plausible for a water soluble compound even if the ability of chromium (III) to penetrate biological membranes is limited because chromium (III) is known to form complexes with biological ligands which enhance penetration. Chromium (III) is absorbed from the normal diet in very low amounts, about 5 - 10% of inhaled water-soluble chromium (III) aerosols were taken up by circulating blood within hours to one day, and water-soluble (III) compounds are able to cross the skin penetration barrier and enter the epidermis.

A significant fraction of chromium appears to be absorbed into the blood and then distributed widely to parenchymal organs. Inhalation and intratracheal studies show that chromium (III) chloride is retained in the lung in proportion to the dose and is cleared realtively slowly from this organ.

Chromium (III) is mainly excreted in the faeces and urine. The delayed elimination seen in studies with water-soluble chromium (III) is consistent with intracellular binding.