1,2,3-Propanetricarboxylic acid, 2-hydroxy-, chromium(3+) salt (1:1)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

Literature review

Type of information:

other: Literature review

Adequacy of study:

key study

Study period:

Assessment

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Despite the absence of specific toxicokinetic data from animal testing on the metal, the fact that chromium is present is food and is considered an essential element for metabolism suggests that mechanisms exist for absorption, distribution and excretion and that the metal is not accumulative

Citric acid and associated salts are found in many foods and are formed in cells as a metabolite from glycolysis. There is no toxicity threshold for repeated exposure in humans

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Version / remarks:

Assessment

Principles of method if other than guideline:

Assessment of agency reviews: Much of the information cited is taken from European Scientific Committee for food safety using assessments for the use of chromium as food supplements.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

614-626-2

EC Number:

614-626-2

Cas Number:

685853-81-0

Molecular formula:

Cr C6H5O7

IUPAC Name:

614-626-2

Test material form:

solid: particulate/powder

Details on test material:

Batch number of test material: C-01-3472
Material was oven-dried at 105°C. This was considered not to have an adverse impact on the nature of the substance, but at this temperature may have still contained some water of hydration.

Specific details on test material used for the study:

Assessment based on chromium ions and citric

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The rate of absorption will depend greatly on the solubility of the salt, but on ingestion, it is likely that there will be significant dissociation in the stomach at low pH.However, an oral gavage study for chromium oxide reported coloured faeces suggesting a large proportion is not absorbed if ingested in large quantities. There is no direct evidence of absorption dermally, but data suggest that sensitisation can occur from contact with the skin which implies some movement of ions at least through the outer layers of skin. A study looking at effects on reproduction by inhalation at maximum achievable levels failed to show any changes in organs or reproductive parameters and it is not conclusive whether absorption can occur by inhalation.

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. Some blood samples and 24-h urine were also examined, and no radioactive chromium was detected.[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].

Details on distribution in tissues:

No adverse systemic effects were observed in reported toxicity tests, other than perhaps effects to reproductive organs at very high concentrations. Hepatic and renal chromium concentrations in rats were roughly 2- to 6-fold greater when chromium picolinate was fed compared to chromium chloride. Due to the natural presence of chelating agents in the diet the bioavailability of chromium from food can vary significantly and although this demonstrates distribution, as an essential element, it is accepted that at least ‘normal’ concentrations will be actively distributed

Details on excretion:

Since there is a general background dietary intake of chromium and no evidence of accumulation, levels of excretion will normally match levels of intake.Most work on excretion of chromium is linked to elimination of chromium VI ions.Urinary chromium excretion of excess chromium following work exposure reflected absorption over the previous one to two days in an occupational setting. A urinary chromium concentration of 40 μg/L to 50 μg/l was reported immediately after a work shift, compared to a reported background level of typically less than 10 μg/l.These reports from workers showed that elimination of excess chromium was rapid and it is also worth noting that although exposure in these cases were to chromium VI, there had been conversion to chromium III prior to elimination.

Citrates are metabolised and not typically excreted in urine

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

Chromium is considered to be an essential part of glucose metabolic processes, but precise mechanisms have not been described. Chromium III will not itself metabolise, but will be linked into chelates where ion-exchange will occur.

Applicant's summary and conclusion

Conclusions:

Despite the absence of specific toxicokinetic data from animal testing on the metal, the fact that chromium is present is food and is considered an essential element for metabolism suggests that mechanisms exist for absorption, distribution and excretion and that the metal is not accumulative.

Executive summary:

It is clear from data presented that the bioavailability is dependent in part on the solubility (dissociation). But even the least soluble salts will be sufficiently soluble under acidic stomach conditions to significantly absorb.

 

There is no direct evidence of absorption by dermal route, but data indicates that chromium is potentially sensitising and this would imply a degree of absorption through the skin. There is also no indication of respiratory.

 

As an essential element, chromium is transportable in the body, but in the absence of chronic toxic effects, there is no evidence of specific target organ effects.

 

Chromium will be excreted as part of natural balance of ions in animals and there is no evidence of accumulation.