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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Expert Statement
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Expert statement
Title:
Unnamed
Report date:
2012

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Assessment of the toxicokinetic behavior of the substance to the extent that can be derived from the relevant available information.
GLP compliance:
no

Test material

Constituent 1
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Name of test material: 5-ethyl-2-methylpyridine
Radiolabelling:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
5 Ethyl 2 methylpyridine is a colorless, clear liquid with characteristic, unpleasant odor. The substance has a molecular weight of 121.18 g/mol, exerts a vapor pressure of 1.853 hPa at 20 °C, a log Pow of 2.1 and is very soluble in water with 12000 mg/L at 20 °C. Based on the determined vapor pressure the substance may volatilize and thus be potentially inhaled as a vapor. However, the very high water solubility, relatively low log octanol water partition coefficient and low molecular weight suggest greater potential for absorption across the skin and gastrointestinal tract.
Upon oral administration uptake of 5-Ethyl-2-methylpyridine is limited by its potential for ionization in neutral and acidic environments (pKa = 6.51). However, due to its low molecular weight and high water solubility the substance has potential to pass through aqueous pores or passage across membranes, e.g. with the bulk passage of water. Based on the results obtained in acute oral toxicity testing (LD50 = 710 mg/kg bw) absorption may occur.
Following inhalation of vapor or aerosols 5-Ethyl-2-methylpyridine may be absorbed directly across the respiratory tract epithelium. Due to the high water solubility and low molecular weight there is also potential for absorption through aqueous pores. Based on the inhalation toxicity data (2.67 mg/L) absorption via the lungs may occur.
Upon exposure to the skin the substance ionization may limit passage across biological membranes. However, the substance has some potential for dermal absorption due to its high water solubility and logPow of 2.39. Based on the acute dermal toxicity data dermal absorption may occur.
Details on distribution in tissues:
Following uptake and becoming bioavailable 5-Ethyl-2-methylpyridine and its metabolites are likely to distribute throughout the blood and intracellular compartments of the organism. Distribution may be limited by the rate of diffusion across membranes. No specific target tissue is known. Based on logPow and the calculated bioaccumulation factor (BCF = 1.244, Epiwin, v4.0) bioaccumulation is not expected.
Details on excretion:
Based on its molecular weight, water solubility and pKa the parent compound 5-Ethyl-2-methylpyridine is likely to be excreted via the urine. Depending on the degree of conjugation, some metabolites may be excreted via bile and faeces. However, the likely predominant pathway for excretion is urine.

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
There is no experimental data on the metabolism of 5-Ethyl-2-methylpyridine. Phase I reactions catalysed by cytochrome P450 or flavin containing monooxygenase may introduce polar groups into the molecule. Phase II conjugation reactions may add charged species such as glutathione (GSH), sulfate, glycine, or glucuronic acid, rendering the molecule less toxic. Based on data available for pyridine and alkylpridines, oxidation of the nitrogen atom and all the carbon atoms of the pyridine ring are likely. Further, heterocyclic nitrogen atoms can be candidates for methylation and, thus, N-methylation, even though less common, may also occur.
It is unlikely that metabolism will render the parent compound or its degradation products more toxic. This assumption is supported by results obtained in a sub-acute repeated dose toxicity test as well as an in vitro Ames test, two chromosome aberration tests and a HPRT assay without and with metabolic activation. In all three assays no significant increases in toxicity were noted, in the presence of a rodent microsomal S9-fraction. This clearly indicates that formation of reactive metabolites is unlikely.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The main routes of exposure for 5-Ethyl-2-methylpyridine are through inhalation of vapors and skin/eye contact with liquid. Following uptake the parent compound and its metabolites may be distributed throughout the organism. Bioaccumulation is considered not likely. Metabolism may render the substance more polar and less toxic before excretion. There is no indication for the formation of more toxic metabolites. Elimination of parent and degradation products is most likely via urine and to a lesser extent via bile and faeces.
Executive summary:

An assessment of the toxicokinetic behavior of the substance to the extent that can be derived from the relevant available information was carried out. The main routes of exposure for 5-Ethyl-2-methylpyridine are through inhalation of vapors and skin/eye contact with liquid. Following uptake the parent compound and its metabolites may be distributed throughout the organism. Bioaccumulation is considered not likely. Metabolism may render the substance more polar and less toxic before excretion. There is no indication for the formation of more toxic metabolites. Elimination of parent and degradation products is most likely via urine and to a lesser extent via bile and faeces.