N,N''-(isobutylidene)diurea

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result:  Data on basic toxicokinetics is available from experiments with sheep (Bergner, Görsch and Adam, 1978; Bergner and Görsch, 1979; Görsch, 1980).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Data on basic toxicokinetics is available from experiments with sheep (Bergner, Görsch and Adam, 1978; Bergner and Görsch, 1979; Görsch, 1980). However, since sheep are ruminants, the results of these studies are only partially relevant for man.

IBDU is soluble in water to a certain extend (0.3 - 3 g/l), has a molecular weight of 174.2 and a log Pow of -0.903. Water-soluble substances will readily dissolve into the gastrointestinal fluids. In addition, substances with a low molecular weight (less than 200) may pass through aqueous pores or be carried through the epithelial barrier by the bulk passage of water. Log Pow values in a range of -1 to 4 are favorable for absorption by passive diffusion. It is therefore quite likely, that IBDU will be partially absorbed within the gastrointestinal tract in humans. This idea is supported by the fact that some minor signs of systemic toxicity were observed in studies with rats. IBDU that was not absorbed in the gastrointestinal tract will be excreted via the feces. It can be expected that IBDU which was absorbed will be metabolized at least to a certain extend as it was seen in sheep, which either had no or only small amounts of IBDU present in their blood. Excretion of IBDU or its metabolites is likely to partially happen via the urine as small amounts of IBDU were observed in the urine of sheep. In addition, the accumulation of the alpha-2-u-globulin in male rats supports this idea. Carbon atoms originating from IBDU may be exhaled in form of CO2 and nitrogen atoms may be integrated into proteins as it was seen in sheep.

Discussion on bioaccumulation potential result:

In three out of four sheep, IBDU was not detectable in blood plasma samples taken at 2.5, 7.25 and 24 hours after oral intake of a 15N-IBDU containing diet (ca 1260 mg/kg bw and day). In the other animal, sacrificed at 12 hours after oral intake, 173 mg IBDU/l (ca. 2.2 % of the IBDU intake was detected in plasma). The blood plasma of another sheep with a ligature at the abomasus entry was found to contain up to 180 mg IBDU/l. This finding is regarded as evidence of the possibility of IBDU to be absorbed through the rumen wall. At 7.25 h, 40 % of the 15N in the rumen was in the form of IBDU, after 12 hours it was 10 % indicating that IBDU undergoes partial decomposition in the rumen.

Only low amounts of unchanged IBDU (max. 1 % of intake) were detected in the urine within 24 hours. The passing of nitrogen from IBDU into the body pool was assumed from recovery experiments, which demonstrated the presence of 15N in plasma proteins and liver. (Bergner, Görsch and Adam, 1978; Bergner and Görsch, 1979; Görsch, 1980).

 

Two sheep received 30 g IBDU with 1259 mg 15N-IBDU and 680 μCi 14C-IBDU (C1 labelled) via the rumen fistula. The animals were placed in respiration cages. The peak of specific 14C-CO2 activity in the expired air (including ruminal gas) was observed 2 h after beginning of the experiment with, about 50 % of the 14C applied being found in the expired air until sacrifice at day 7. Incorporation of 15N into the protein fraction of blood was demonstrated. 3.5 % of the 14C and 23 % of the 15N were excreted in the urine within 6 days. 20 % of the 15N in urine could be detected as 14C-isobutyl residues. An average of 22 % of the 15N applied was excreted in faeces (3.8 % of the applied 14C) (Bergner and Görsch, 1979; Görsch, 1980).