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In an absorption and excretion study according to OECD 417 Na3NTA was administered to male Wistar rats at dose levels of 500 mg/kg and 25 mg/kg (BASF, 1997). Na3NTA was rapidly absorbed from the gastrointestinal tract after single and repeated oral administration. Absorption, however, was incomplete amounting to about 50 % of the dose applied. Excretion was rapid with a urinary excretion half-life of about 5-6 hours. The experiment did not indicate any bioaccumulation potential.

In beagle dogs absorption of 20 mg/kg Na2NTA was extensive and rapid (Budny, 1972). 80% of oral applied NTA appeared in the urine after 72h. 75 % after 4 hr. Peak concentration in blood was reached after 75 min. Since 96 % of an i.v. administered dose appeared in the urine, with only a negligible amount in the feces, it can be concluded that no enterohepatic circulation occurred. The rapid and extensive excretion is consistent with the low overall tissue deposition of NTA. The greatest tissue deposition was in bones (2-3 pg/g); the next highest in the kidneys.

A combined toxicokinetic/teratologinicity study in mice showed that the distribution patterns of i.v. injection and p.o. administration were similar and characterized by high uptake of radioactivity in the skeleton compared to other compartments (Tjälve 1972). The radioactivity was rapidly accumulated and was still present after 48 hours. In pregnant mice, a low uptake of the test substance also in the skeleton of fetuses could be observed and in addition to a comparable high accumulation in the walls of the uterus. Although a low percentage of NTA was deposited in the skeleton, no clear adverse effect of NTA treatment on the bone was seen in rats in a 2-year feeding study at concentrations of up to 322 mg/kg/d (Nixon et al., 1972; section 7.5.1) or in fetal development (Tjälve, 1972; section7.8.2). An examination in bones showed a dose-related increased NTA content. Histological examination of bone showed no differences in the amount of osteoid tissue or widths of the epiphyseal plates between samples from control animals and animals of the high dose group (Budny 1973; section 7.5.1).

Budny & Arnold (1973) examined the oral absorption of Na3NTA in 8 human volunteers (IUCLID section 7.10.3). NTA was poorly absorbed and rapidly excreted as indicated by a fraction of 12% recovered in Urin within 120 h (77% recovered in feces). Blood concentration peak occurred within 1 -2 h. After 12 h only traces of radioactivity were found in blood. NTA was not metabolized to a significant extend. > 96% of the urinay radioactivity was found to be uncharged NTA. There was no evidence for enterohepatic circulation.

The human data suggest a pronounced species differences: 12% of the total dose was excreted in human urine in 2h. This was 87% of the absorbed dose (77% were recovered in feces). An absorption rate for human between 10 and 20 % was concluded. In contrast in dogs only 3% of the applied dose was recovered in the feces. Up to 97% were absorbed and rapidly excreted in urine. In rats only approximately 50% of the applied dose was absorbed, 80% of this dose was excreted in urine in 24h. These data suggest that human absorption rate is 1/4 of the that observed in rats or dogs.

 

Data on dermal absorption are not available form animal studies or reported in humans. However, dermal penetration was assessed in vitro (BASF 2008).14C-Na3NTA was applied to human skin preparations in a Franz-type diffusion cells as 40 % and 1% aqueous dilution. At high concentration exposure was stopped after 5 min to avoid severe skin damage that would greatly enhance penetration. 0.001 % (n=5) of the substance was absorbed. However, the applied dose was washed off after 5 min in this setting, so this experimental data do not allow drawing conclusions on elongated exposure to 40% Na3NTA. At low concentration exposure was stopped after 6 h. Absorption ranged between 0.042 and 0.472 % (n=5) during a sampling period of 24 hr. The presence of a lag time of absorption (about 1.6 h) underlines the functional diffusion barrier of human skin against NTA preparation.