A SHORT-TERM CROSS-OVER STUDY ON ORAL-ADMINISTRATION OF SOLUBLE AND INSOLUBLE COBALT COMPOUNDS - SEX-DIFFERENCES IN BIOLOGICAL LEVELS

This paper describes a blind cross-over study on the gastrointestinal uptake of soluble and insoluble cobalt compounds (8.5 mumol/day) in 12 male and 11 female volunteers. In a controlled study it was found tha t the gastrointestinal uptake of the soluble cobalt compound cobalt ch loride was considerably higher than the uptake of the insoluble cobalt compound cobalt oxide (urine ranges: < 0.17-4373 and < 0.17-14.6 nmol /mmol creatinine, respectively). Surprisingly, it was shown that inges tion of controlled amounts of soluble cobalt compound resulted in sign ificantly higher urinary cobalt levels (P<0.01) in females (median: 10 9.7 nmol/mmol creatinine) than in males (median: 38.4 nmol/mmol creati nine). The results suggest that the gastrointestinal uptake of cobalt is higher for females than males. The present study shows that the nor mal levels of cobalt in blood and urine in a non-random-selected group of Danes are low. As the fraction of values below the detection limit of the analytical method was 0.19 and 0.33 for urinary cobalt in fema les and males, respectively, distribution-free one-sided tolerance int ervals were chosen to describe the values. The precision of the estima te of the tolerance intervals was expressed as coverage intervals. In females the 95% one-sided tolerance limit calculated for cobalt in blo od and urine was 8.48 and 55.10 nmol/l with coverage intervals of 90% +/- 6.5% and 95% +/- 4.2% at a probability of 0.95, respectively. Even though the studied groups of males and females were not representativ e for the general population, the study indicates that oral exposure m ay be important in occupational settings. In this context the estimate d tolerance limits for cobalt at normal levels may be used as indicati ve values, i.e. stating the order of magnitude to be expected.