Di(µ-2,2´,2´´-nitrilotris(ethanol)-diperchlorato)dinatrium

Endpoint summary

Description of key information

No bioaccumulation potential is expected.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

There is no specific requirement to generate Toxicokinetic information according to REACH Regulation (EC) No 1907/2006. Annex I, Section 1.0.2 states that “the human health hazard assessment shall consider the toxicokinetic profile (i.e. absorption, metabolism, distribution and elimination) of the substance”. Furthermore, REACH announces in Annex VIII (Section 8.8.1) that one should perform “assessment of the toxicokinetic behaviour of the substance to the extent that can be derived from the relevant available information”. The toxicokinetic behaviour derived from available data on the dissociation substances but also taking in great consideration the physicochemical properites of the substance. Further testing is not considered as necessary since the toxicological profile of the substance (and dissociation substances) can be predicted/ evaluated. The assessment of TK profile (absorption, metabolism, distribution, excretion) is therefore assessed to the extent that can be derived from the relevant available information.

Absorption by the dermal and inhalation route is not expected; the route of maximum absorption considered as potentially relevant for substance is the oral one. Once in the blood the substance is expected to dissociate into triethanolamine, sodium and perchlorate following therefore their distribution, metabolism and excretion profile.

Perchlorate is readily and extensively absorbed from the gastrointestinal tract in both humans and rats. Peak blood concentrations in rat by 3 h, in humans perchlorate in urine is noted from 10 minutes after ingestion. Following absorption, it is widely distributed in the body (human serum, plasma, urine, saliva and breast milk) with the highest concentrations occuring in the thyroid. Evidence indicates that it undergoes very little, if any metabolism. Then it is rapidly excreted mainly in the urine as unchanged parent compound (half-life in rats is 8 -20 hrs, in humans is 8 -12 hrs). Almost all radiolabelled perchlorate (99.5 %) is recovered from urine within 48 hrs following inravenous administrtion in rats.

In a comparative pharmacokinetics and metabolism study on triethanolamine, dermal absorption of [¹⁴C]-triethanolamine was slower and less extensive in F344 rats than in C3H/HeJ mice, although the tissue distribution of radioactivity was similar. In mice that received a single 1000 mg/kg dermal application, approximately 60 % of the radioactivity was recovered from the urine and 20 % was recovered from the feces 48 hours after dosing; less than 10 % was detected in the skin at the site of application. More than 95 % of the radioactivity recovered in the urine was identified as the parent compound, indicating that triethanolamine does not undergo extensive biotransformation in mice. The serum half-life of [¹⁴C]-triethanolamine in mice was approximately 9.5 hrs after either a 1 mg/kg intravenous injection or a 1000 mg/kg dermal application. In rats, a single oral dose (2 to 3 mg/kg) of [¹⁴C]-triethanolamine was rapidly absorbed and excreted mainly in the urine as unchanged parent compound. Twenty-four hours after dosing, 53 % of the radioactivity was recovered in the urine and 20 % was recovered in the feces. Also, after multiple oral administration to male and female rats, triethanolamine was mainly excreted unchanged. The urinary and faecal excretion ratio of unchanged triethanolamine remained constant throughout the treatment period (for five to six days) in both males and females. A small amount of triethanolamine (1.4–2.7 %) was excreted as glucuronide conjugates.