Benzonitrile, 3,3'-(2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]pyrrole-1,4-diyl)bis-

Endpoint summary

Description of key information

Absorption, distribution, metabolism and excretion of the test item were not examined. Reliable data on a structural analogue are available. For this purpose, 14C-labelled substance was administered orally at two target dose levels of 100 mg/kg (low dose) and 1000 mg/kg (high dose) to male rats and radioactivity appearing in urine, feces, blood/plasma and organs/ tissues was followed for 168 hours. At both dose levels, the very low radioactivity levels found in blood and plasma as well as the minimal amounts excreted via the urine indicated 1 that 14C-material was absorbed to a negligible extent and therefore not bioavailable after single oral administration to rats within the used dose range.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption, distribution, metabolism and excretion of the test item were not examined. Reliable data on a structural analogue are available. Both substances are pigments and share high similarity in structure and are of low solubilitx in water (< 0.1 mg/l). The analogue has a slightly higher molecular weight which gives an additional safety margin.

To evaluate a possible toxicological hazard and the bioavailability of the test material (analogue) in man, the objectives of the present toxicokinetic study were to follow the absorption, distribution and excretion in rats. For this purpose, 14C-labelled substance was administered orally at two target dose levels of 100 mg/kg (low dose) and 1000 mg/kg (high dose) to male rats and radioactivity appearing in urine, feces, blood/plasma and organs/ tissues was followed for 168 hours. Due to lack of solubility of the test article, actual amounts of 14C-material present in the various stock suspertsions and suspensions for application were only indirectly determined by means of weighing.

At 168 hours after the administration, only very low amounts (0.3 % and 0.6 %) of radioactivity were found in the urine at the low and high dose level, respectively. Already after 24 hours, radioactivity in the urine amounted to 0.3 % and 0.4 %, respectively, and may for the most part originate from a contamination via the feces. Accordingly, excretion of the compound proceeded almost exclusively via the feces and amounted after 168 hours, on average, to 119.7 % and 96.0 % at the low and high dose level, respectively. Already after 24 hours, fecal excretion accounted for 101.4 % (low dose level) and 79.7 % (high dose level) of the radioactivity administered. Together with the cage wash (1.8 % and 7.7 %), total excreted radioactivity amounted to 121.5 % and 104.3 % at the low and high dose level, respectively. Taking into account the very low radioactivity levels found in blood and plasma, no elimination kinetics and no area under the curves could be calculated. Except for intestinal tract with contents, residual radioactivity levels found at 168 hours after low and high dose level administration in all organs/tissues, blood/plasma and residual carcass were negligible.

In conclusion, at both dose levels, the very low radioactivity levels found in blood and plasma as well as the minimal amounts excreted via the urine indicated 1 that 14C-material was absorbed to a negligible extent and therefore not bioavailable after single oral administration to rats within the used dose range.