Reaction mass of 2-[[[2-[(2-aminoethyl)amino]ethyl]amino]carbonyl]-benzoic acid and 2,2' -[iminobis(2,1-ethanediyliminocarbonyl)]bis-benzoic acid and 7,8,9,10,11,12,20,21,22,23,24,25-dodecahydrodibenzo[i,t] [1,4,7,12,15,18] hexaazacyclodocosine-5,13,18,26(6H,19H)-tetrone

Endpoint summary

Description of key information

For oral, dermal and inhalation route, the default values from the REACH guidance (Chapter 8, R.8.4.2) are used fro DNEL derivation: 100% for inhalation, 50% for oral and 50% for dermal.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

In accordance with Annex VIII (point 8.8) of Regulation (EC) No 1907/2006 (REACH), a paper-based toxicokinetic assessment has been conducted for the item, 1,3 -isobenzofuradione, reaction product with DETA. Summaries of studies were reviewed by a

qualified toxicologist with a view to fulfilling the requirements of Annex VIII, point 8.8 of REACH. The list of data used for the assessment is given in section 5. The assessment of the likely toxicokinetic behaviour of the item was provided to the extent that can be

derived from the relevant available information at the time of the assessment. The assessment is based on the Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, November 2012). The assessment was conducted in June 2015.

The test item is a yellow powder as listed in Section 2.1. The low vapour pressure value (6.7 E-5 Pa at 25 ºC) and predicted negative explosive and oxidising properties shows that the substance is of low volatility therefore inhalation is not a significant route of exposure. Thsi is confirmed by an acute inhalation study that did not induce mortality in rats. The test item was not indicated to be a sensitizer. The results from the repeated dose reproductive screening study in rats (Rashid, 2014) did not produce any sign of systemic toxicity at 1000 mg/kg bw/day, and there was no effect on offspring survival, growth and development rates to a dosage of 1000 mg/kg bw/day.

Water soluble substances may readily dissolve into the gastro intestinal fluids. However. absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. This seems to be confirmed by the absence of any sign of systemic toxicity observed during a repetaed dose toxicity study. However, mortality observed at very high dose levels in acute toxicity studies proves that the substance is able to be absorbed by the gastointestinal tract. The high water solubility and log Pow value suggests that the substace may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Furthermore, in the available acute dermal toxicity study no effects were observed. Therefore, dermal uptake will be very unlikely. For oral, dermal and inhalation route, the default factor values from the REACH guidance (Chapter 8, R.8.4.2) are used fro DNEL derivation: 2 for inhalation, 1 for oral and 1 for dermal.

There is no evidence to indicate the route of excretion but water-soluble products are favourable for urinary excretion and therefore this route may be the major route of excretion of the substance. Biliary excretion may be also considered to be a plausible route of excretion of the test item via the faeces.

The available information suggests that some absorption of the test substance would take place from the gastrointestinal tract. Some limited absorption may also be possible through the skin.