Pentyl 2-cyano-(3-(6-methoxybenzothiazol-2-ylimino)-2,3-dihydro-1H-isoindol-1-ylidene)acetate

Endpoint summary

Description of key information

Toxicokinetic assessment

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic parameters such as absorption, distribution, metabolism and excretion do represent the essential toxicological profile of a substance. The evaluation of the toxicokinetic properties of FC 84508 PK is based on the results of subsequent toxicological endpoints: acute oral toxicity, acute dermal toxicity, skin irritation, sensitization, Ames test, the HPRT assay, the in vitro cytogenetic study of subacute oral toxicity , with the additional inclusion of physico-chemical data, such as the solubility, partition coefficient, and the hydrolytic stability.

Toxicological Profile:

Application of 2000 mg/kg bw leads in the acute oral toxicity study to no clinical symptoms and no lethality. Orange discolored faeces were observed. Other macroscopic effects were not observed. This results in an LD50 of> 2000 mg/kg bw. The dermal treatment with 2000 mg/kg bw also led to no toxicologically relevant symptoms. FC 84508 PK is not a skin irritant and non-sensitizing. Based on the results of acute dermal toxicity study, as well as the significantly lipophilic properties FC 84508 PK has no significant dermal absorption potential. FC 84508 PK is mutagenic in the Ames test with Salmonella typhimurium TA 100, TA 1535, TA 1537 and TA 98 with metabolic activation, but not in the HPRT test with mammalian cells. FC 84508 PK does not induce chromosome aberrations in V79 hamster cells in vitro. In the subacute (28 days) oral toxicity study in rats, daily doses up to 1000 mg/kg bw caused no compound-related lethality. The haematological and clinical chemical parameters, as well as the specific organ weights were unaffected. Histopathological examinations were unremarkable. Macroscopically, no substance-specific effect was found. Based on the available data, a NOAEL/NOEL of 1000 mg/kg/body weight was determined.

The results of basic toxicity testing give no reason to anticipate unusual characteristics with regards to the toxicokinetic behaviour of FC PK 84508. The dye has a very low acute toxic potential and no or only a very low dermal absorption potential. The results of the subacute study show no absorption through the gastrointestinal tract. Although FC PK 84508 has shown a tendency to mutagenic effects in bacteria, no mutagenicity was observed in the HPRT test in mammalian cells.

The steady-state bioconcentration factor (BCFss) was determined in an in vivo bioaccumulation study in fish using carp (Cyprinus carpio) according to a Japanese test guideline that is compliant with OECD guideline 305 and EC test method C.13. The BCFss was found to be 38 at the high test concentration (0.1 mg/L) and 236 at the low test concentration. The substance is therefore not bioaccumulative.

Summary:

The results of the toxicological studies provide no unusual toxicokinetic behaviour of FC 84508 PK. No evidence of a significant systemic potential were observed. Bioaccumulation cannot be excluded due to the lipophilic nature, was however not observed in the 28-day study and in an in vivo bioaccumulation study in fish. The substance is therefore not bioaccumulative.