Registration Dossier

Administrative data

Link to relevant study record(s)

Reference
Endpoint:
basic toxicokinetics
Type of information:
other: Expert Statement
Adequacy of study:
key study
Study period:
Sep 2012
Reliability:
4 (not assignable)
Principles of method if other than guideline:
The Toxicokinetic Assessment is meant to fulfil the requirement as defined in the REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 18 December 2006 requests in Annex VIII, point 8.8.1:
"Assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information."
GLP compliance:
no
Radiolabelling:
other:
Executive summary:

No ADME and dermal absorption study with the test substance are available. However, a series of acute and repeated dose toxicity studies give an indication about the bioavailability after oral and dermal application. In acute and repeated dose oral toxicity studies with 2-ethylanthraquinone systemic toxicity was seen leading to the conclusion that the test substance is bioavailable after oral application. There are also indications that the yellow coloured test substance is excreted with the urine, since in two repeated dose oral toxicity studies a dose related increase in the intensity of yellow-amber coloured urine is described.

After dermal application of 20 g test substance/kg bw in a acute dermal toxicity test and dermal application in a Local Lymph Node Assay, no systemic effects could be observed. This could indicate that the dermal absorption of 2-ethylanthraquinone is low. Furthermore the high octanol/water partition coefficient (log Pow = 4.6) of the substance could result in a low skin penetration.

Due to the very low vapour pressure (1.2 x 10^-4 Pa at 25C°) inhalation exposure is only possible via aerosols of solid particles or dissolved material. It is assumed that the substance is bioavailable via the lungs. 

The systemic effects (mainly changes in the hematopoiesis) indicate that the substance is distributed throughout the body after oral absorption. Due to the low water solubility and the high octanol/water partition coefficient accumulation in fatty tissues could occur.

The finding that urine was coloured amber-yellow in repeated dose studies might support the conclusion that some amounts of the substance are not metabolised and excreted unchanged via urine. Due to the low water solubility excretion via the bile is most likely.

Description of key information

- accumulation in fatty tissues could occur,

- bioavailable after oral application,

- indications that test substance is excreted with urine,

- dermal absorption expected to be low,

- bioavailability via the lungs is assumed.

Key value for chemical safety assessment

Additional information

No ADME and dermal absorption study with the test substance are available. However, a series of acute and repeated dose toxicity studies give an indication about the bioavailability after oral and dermal application. In acute and repeated dose oral toxicity studies with 2-ethylanthraquinone systemic toxicity was seen leading to the conclusion that the test substance is bioavailable after oral application. There are also indications that the yellow coloured test substance is excreted with the urine, since in two repeated dose oral toxicity studies a dose related increase in the intensity of yellow-amber coloured urine is described.

After dermal application of 20 g test substance/kg bw in a acute dermal toxicity test and dermal application in a Local Lymph Node Assay, no systemic effects could be observed. This could indicate that the dermal absorption of 2-ethylanthraquinone is low. Furthermore the high octanol/water partition coefficient (log Pow = 4.6) of the substance could result in a low skin penetration.

Due to the very low vapour pressure (1.2 x 10^-4 Pa at 25C°) inhalation exposure is only possible via aerosols of solid particles or dissolved material. It is assumed that the substance is bioavailable via the lungs. 

The systemic effects (mainly changes in the hematopoiesis) indicate that the substance is distributed throughout the body after oral absorption. Due to the low water solubility and the high octanol/water partition coefficient accumulation in fatty tissues could occur.

The finding that urine was coloured amber-yellow in repeated dose studies might support the conclusion that some amounts of the substance are not metabolised and excreted unchanged via urine. Due to the low water solubility excretion via the bile is most likely.