1-methylimidazole

Endpoint summary

Description of key information

- studies indicate oral and dermal absorption
- default factors for DNEL derivation

Additional information

No data are available that describe the toxicokinetics of 1-methylimidazole, 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 -Methylimidazole is a liquid with a molecular weight of 82.1038 g/mol. The vapour pressure is 0.3514 hPa at 20 °C, the log Pow value is -0.19 and the water solubility is 1000 g/L.

 

Data from acute and repeated dose toxicity studies:

- Oral toxicity: In an acute oral toxicity study in rats, exposure to ca. 208 to 1664 mg/kg bw 1-methylimidazole by gavage resulted in mortality in rats. The oral LD50 was ca. 1144 mg/kg bw. In a GLP-compliant oral 90-d study (OECD408), 1-methylimidazole at dose levels of 10, 30, or 90 mg/kg bw/day was given to rats by oral gavage. In both male and female high-dose animals non-adverse findings were observed. Thus, the NOAEL for systemic toxicity was 90 mg/kg bw/day. In a GLP-compliant oral teratogenicity study (OECD414), 1-methylimidazole also did not reveal any adverse findings at the same doses, but pre-natal developmental and maternal toxicity was observed at 230 mg/kg bw/d.

- Inhalation toxicity: In an acute inhalation study in rats, exposure to a saturated vapour of 1-methylimidazole at 20 °C no deaths were observed. Due to the low vapour pressure, the technically highest attainable concentration is approximately 1.2 g/m3 when the test substance is evaporated at 20°C (saturated vapour concentration: 0.0412*MG*VP = 1.2 mg/L).

- Dermal toxicity: In an acute dermal toxicity study in rabbits, exposure to 250, 400, 640 mg/kg bw 1-methylimidazole resulted in mortality. Clinical signs included: apathy, accelerated breathing, spasms, salivation, excess lacrimation and narrowed pupils. The LD50 value was determined to be: 400 < LD50 < 640 mg/kg bw.

 

Absorption figures used for the DNEL derivation

The results of the acute oral and the oral repeated dose toxicity studies indicate absorption of the test substance by the oral route. Secondly, 1-methylimidazole 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 1-methylimidazole may be readily absorbed by the gastrointestinal and respiratory tract.

The results of the acute dermal toxicity study do indicate absorption of the test substance by the dermal route. QSAR model DERMWIN (part of the model EPI suite) results in an estimated Kp = 0.000495 cm/hr. According to the user manual of the Danish QSAR database, May 2005 this indicates low dermal absorption (range: very low/low/moderate/high).

Since it is likely that 1-methylimidazole 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, based on the physico-chemical properties of the substance (log Kow < 0 and high water solubility), and based on the estimated Kp, low dermal uptake is expected. However, as in the acute dermal toxicity study mortality and clinical effects were observed, dermal absorption cannot be excluded. Therefore, a default factor of 1 in the case of oral-to-dermal extrapolation is included.