Sodium thiocyanate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study was performed pre-GLP and pre-guideline. The paper considers the kinetics of elimination of thiocyanate, firstly in healthy subjects with normal and with raised levels of chloride intake, and secondly in subjects with renal failure.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Details on test material:

KSCN

Radiolabelling:

no

Test animals

Species:

human

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Results and discussion

Any other information on results incl. tables

The initial concentration of the SCN- in the serum. (by extrapolation) was on average 39 mg/l and 38 mg/1 for the tests with and without NaCl loading, respectively. The apparent distribution volume (Vd) had a mean value of 0.25 l/ kg, or 25% of the body volume. The mean half-life (t1/2) of the thiocyanate was lowered by only 15% from 2.7 to 2.3 days by the NaCl loading. The half-life values in the serum showed a relatively wide scatter for the seven subjects (1.5 to 5 days approx.). The renal thiocyanate-clearance (Clr) had a mean value of 5.65 ml/min with and 4.32 ml/min without the NaCl loading. The basic excretion rate of thiocyanate (UEb) was 23±5 mg/d. Of the amounts administered as doses, 102% (UE%) was found to be the total collected in the urine over fourteen days, after subtracting to allow for the basic excretion. In the subjects with renal failure t he mean creatinine-clearance was 22 ml/min. The mean distribution volume (Vd) was 0.36 l/kg, i.e. higher than in the healthy subjects. The mean elimination half-life (t1/2) was 9 days, i.e. 3 times longer than in the healthy subjects.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
The study has many limitation but the results suggest that there no bioaccumulation occurs.

Executive summary:

The concentration of thiocyanate in the serum of eight test subjects with renal failure and seven healthy control subjects was measured, as it declined with time, after oral doses of thiocyanate or i.v. injections of nitroprusside had been administered. Additional measurements were taken, on the healthy subjects only, of the concentrations of thiocyanate in the urine. and also of the influence of an increased chloride intake on the rate of eliminiation of thiocyanate. For the healthy subjects an elimination half-life of between one and five days (mean c. 3 days) was found. Increasing the chloride elimination rate to approximately twice normal did not significantly speed up the rate of thiocyanate elimination. The amounts of thiocyanate which had been administered as doses reappeared almost exclusively in the urine. For the subjects with renal failure, the elimination half-life had a mean value of approximately nine days. The elimination constants were found to be proportional to the creatinine-clearance rates. The k_e value at a creatinine-clearance of zero ml/min was approximately 15% of the k_e, value at a creatinineclearance rate of 120 ml/min. The distribution volumes for thiocyanate were greater for the patients with renal failure than for the healthy subjects. The conclusions for therapies using nitroprusside are discussed.