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Description of key information

- The toxicity of TMG is based on its strong corrosivity (pH > 12.5). 

- log Pow value between -1 and 4, favouring absorption by passive diffusion; favorable for adsorption with a MW just below 200 g/mol.

- Without substance-specific absorption data, default absorption values are used for DNEL derivation (see ECHA GD R.8.4.2.): 100% for inhalation, 50% for oral absorption and a default factor of 1 in the case of oral-to-dermal extrapolation.

Key value for chemical safety assessment

Additional information

No data are available that describe the toxicokinetics of TMG, CAS 80-70-6, therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

Physical-chemical properties:

1,1,3,3-Tetramethylguanidine (TMG), CAS 80-70-6 is a light yellow, liquid with a characteristic amine-like odour. It has a MW of 115.1768 g/mol, a vapour pressure of 2.9 hPa @20 °C and thus the saturated vapour concentration is calculated to be 13.8 mg/L. It is miscible with water at any ratio and has a log Pow of -0.49 @20 °C. With a pH > 12.5 is is a strong alkaline substance (additional information in IUCLID section 4.7).

Data from acute and repeated dose toxicity studies:

TMG is harmful after single ingestion (LD50 (oral, rat) = 835 mg/kg; 1982).The major pathological findings noted at necropsy were associated with the stomach, gastrointestinal tract and lungs. Data on the irritancy of the test article and the extreme alkalinity of the test article formulations suggest a severe irritant or corrosive effect on the intestinal linings and tissues with the delayed deaths being possibly due to resultant peritonitis. Furthermore, an oral OECD422 study in rat is available with doses of 0, 10, 30 and 100 mg/kg bw/d administered per gavage (2018). The observed adverse findings were erosions in the glandular stomach of some females in the mid and high dose group and considered to be local effects resulting from the basic corrosive properties of TMG. Therefore, the systemic NOAEL in this study is 100 mg/kg bw/d and the local NOAEL is 10 mg/kg bw/d.As TMG is corrosive to the skin (study similar to OECD TG 404; 1982), there are no acute or repeated dose toxicity studies via the inhalatory or the dermal route available. Additionally, TMG is not expected to be skin sensitizing (QSAR, 2017) and was not mutagenic in bacteria and mammalian cell culture (Ames: 2015; HPRT: 2018 and in vitro MNT, 2017).

In conclusion, the results of the acute oral and the oral repeated dose toxicity studies indicate that the toxicity of TMG is based on its strong corrosivity. 

Absorption figures used for the DNEL derivation:

TMG has a log Pow value between -1 and 4, which favors absorption by passive diffusion. Furthermore, the molecular weight just below 200 makes the test substance also favorable for adsorption. Overall, this suggests that TMG may be readily absorbed by the gastrointestinal and respiratory tract. Since it is possible that TMG will be absorbed and in the absence of substance-specific absorption data, the default absorption values from the ECHA GD R.8 (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation and 50% for oral absorption. For dermal absorption, a default factor of 1 in the case of oral-to-dermal extrapolation is included.