Bumetrizole

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There are no studies profiling the compound with CAS No. 3896-11-5 with respect to its toxicokinetic behaviour.

The test substance has a molecular weight of 315.7973 g/mol. It is a slightly yellow powder at room temperature. It has a very poorly solubility in water (< 1 mg/L at 20°C). The vapour pressure of the test substance is determined to be 0.00000075 Pa at 20°C. A log P_0/w is estimated at 5.55.

Absorption

In oral toxicity studies, in which doses from 2000 up to 7750 mg/kg bw were administered by gavage in rats, no peculiarities as in for example, yellowly discoloration of urine and faeces were reported. Death was also absent and registered clinical signs of toxicity mirrored at least in one experiment normal signs that are commonly seen in acute oral toxicity tests i.e. sedation, dyspnoea, curved position and ruffled fur. Results from acute toxicity tests thus give no indications of systemic bioavailability of the test substance via the GIT. However, indirect indications of systemic availability are seen in a 13 week subchronic study in dogs, in which diets containing the test substance at levels of 200, 1000 or 5000 ppm lead to a significant reduction of body weights in females of the highest dose group. After termination of the 13 week treatment, body weights were normalised. In addition, a significant but reversible (4 weeks recovery) increase in liver weights - that however was not accompanied by histological changes - seen in animals of both sexes of the high dose group suggests a functional adaptation of the liver to increased systemic load. A slight increase in relative liver to body weights was also seen in a 90 day study in Wistar rats given the test substance in diet ad libitum at concentrations of 400, 1000, 2500 and 10000 ppm.

In an acute dermal toxicity study in rats (limit dose of 2000 mg/kg bw), no clinical signs of toxicity and no staining of urine or faeces were observed giving no indication of dermal absorption. The test substance does not cause skin irritation, hence enhanced absorption due to damaged skin tissue is not expected. In guinea pigs (GPMT) and mice (LLNA), the potential to cause hypersensitisation after skin contact was absent. In view of these findings coupled with the fact that the test substance has very low water solubility and a log Po/w of 5.55, systemic bioavailability via dermal absorption would not be expected.

No reliable inhalation studies are available. However, given its very low vapour pressure, and low water solubility, systemic availability after exposure to vapours or dust particle of the test substance is expected to be low.

Distribution and accumulation

Due to its high lipophilic character (log Po/w of 5.55), the test substance if systemic available would be expected to distribute into cells with the intracellular concentration probably higher than extracellular concentration particularly in fatty tissues. Furthermore, due to its high lipophilicity, upon systemic availability there may be a potential to accumulate especially if exposure to the test substance should be frequent.