L-Aspartic acid, N,N'-1,2-ethanediylbis-

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
In reliable studies, at least 5% of radiolabelled trisodium EDDS was considered absorbed after 72 h in male and female rats following single gavage administration and 11% following dermal application. In the oral studies, trisodium EDDS was rapidly eliminated, mainly in the faeces (about 75% of the administered dose), whereas in the dermal studies less than 9% was excreted (the majority remained on the skin). Low amounts of radioactivity were detected in the organs and tissues examined in both studies (Ferinandi, 1995).
Good quality studies, involving single gavage administration of radiolabelled trisodium EDDS at about 2 g/kg bw to male (Powers, 1993a) and female (Powers, 1993b) rats, demonstrate that the bone marrow is exposed to EDDS and/or its metabolites following oral dosing under conditions similar to those employed in an in vivo cytogenetic study (Putman, 1994).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

In a GLP study conducted accorrding to a protocol similar to OECD Guideline 417, the absorption, distribution and elimination of 14C-labelled trisodium EDDS was determined in male and female Wistar rats. The radiolabelled test substance was administered by single oral gavage (in water) to five rats of each sex at a dose level of 0.5 mg/rat (about 2-3 mg/kg bw) and the animals placed in individual metabolism cages. Urine, faeces and cage washes were collected at 24, 48 and 72 h and expired air in 12, 24, 36, 48 and 72 h samples. At study termination (72 h), blood samples were taken and plasma separated and selected tissues and gastrointestinal contents were collected and the levels of radioactivity were determined by liquid scintillation counting (after solubilising the tissues as necessary). Trisodium EDDS was rapidly excreted, mainly in the faeces. In the first 24 h, approximately 62 and 70% of the administered dose, respectively in males and females, was excreted in the faeces, and after 72 h about 75% excreted in the faeces. At least 5% of the test substance was considered absorbed as determined by the amount of radioactivity in urine, expired air and in the tissues (additional material may have been collected in the cage washes and faeces). The combined mean radioactivity content of blood and tissues (including carcass) was 0.136 and 0.153% of the administered dose in males and females, respectively. No statistically significant gender differences were evident in the absorption, distribution or excretion patterns (Ferdinandi, 1995).

 

In a GLP study conducted according to a protocol similar to OECD Guideline 417, the absorption, distribution and elimination of 14C-trisodium EDDS was determined in male and female Wistar rats. The radiolabelled test substance was applied (in water) at 4-5 mg/kg bw in a glass chamber to the shaved skin of five rats of each sex for 72 h. Urine, faeces, cage washings and expired air were collected at intervals throughout the study period and the radioactive content was measured. At study termination, levels of radioactivity were determined in adipose tissue, brain, bone marrow, femur bone, gonads, heart, gastrointestinal tract, gastrointestinal contents, kidneys, liver, lungs, muscle, pancreas, spleen, carcass, skin from the treatment site and adjacent sites. The total recovery of radioactivity from all sources was 59.1% in males and 62.8% in females. This mainly represented unabsorbed material found at the skin treatment site (about 40%) and in the dermal chamber washings (about 10%). Only about 11% of the applied dose was considered absorbed in males and 5% in females during the 72-h exposure period, with less than 9% recovered in the excreta (urine, faeces, cage wash and expired air). Low amounts of radioactivity were detected in the organs and tissues examined, ranging from 0% to up to 1.2% in the male carcass (Ferdinandi, 1995).

 

In good-quality studies, trisodium EDDS was studied for its ability to reach the bone marrow in male (Powers, 1993a) and female (Powers, 1993b) rats, under conditions similar to those used in in vivo cytogenetic assays. Groups of three male rats per time point were administered a single dose of (14C-) radiolabelled trisodium EDDS by gavage at 2106 mg/kg bw (in water) and necropsied at 2, 4, 8, 15, 24, 32, 48, 56 or 72 h. Radioactivity was measured in the blood, plasma, testes, liver, kidneys and bone marrow (femur). Peak levels in liver, kidney, testes and bone marrow were found at between 15-32 h post-dose; the peak levels were 6.8, 42, 27 and 37 µg/g tissue for the testes, kidneys, liver and bone marrow, respectively. In blood and plasma, the levels were relatively constant at about 7 and 11 µg/g, respectively, during the first 32-48 h, before decreasing to about 4.5 µg/g at study termination (Powers, 1993a). Groups of three female rats per time point were administered a single dose of (14C-) radiolabelled trisodium EDDS by gavage at 2053 mg/kg bw (in water) and necropsied at 2, 8, 15, 25, 32, 37, 48, 56 and 72 h post-dose. Radioactivity was measured in the blood, plasma, liver, kidneys, ovaries and bone marrow (femur). Highest levels of radioactivity were found in the kidney and liver (peaking within 8 h post-dose). No distinct rise to peak radioactivity was seen in any of the tissues analysed. Plasma radioactivity was highest at 8 h post-dose, and blood and ovary radioactivity at 15 h post-treatment, and then slowly decreased. Liver, kidney and bone marrow levels were highest at 2, 8 and 24 h, respectively, and then were slowly reduced (Powers, 1993b). Results of these studies demonstrate that bone marrow is exposed to EDDS and/or its metabolites following oral (gavage) dosing under conditions similar to those employed in an in vivo cytogenetic study (Putman, 1994).

[Data on trisodium EDDS is considered relevant to use for understanding the basic toxicokinetics of EDDS acid, and is acceptable for using as read-across information.]