2-(chloromethyl)-4-methylquinazoline

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

The study represents a summary of physico-chemical, toxicological and eco-toxicological experimental studies that had previously been conducted with the test substance and on that basis makes assumptions for basic toxicokinetics.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Guideline:

other: Summary and evaluation of experimental results

Details on exposure:

n/a

Remarks:

n/a

Details on absorption:

Based on physical-chemical properties the test item may penetrate skin. The log Kow-value and water solubility predict moderate to favoured dermal penetration, respectively. Further, irritation and corrosion properties of the substance may produce skin damage and thus enhance penetration.
Administered orally, the test item is likely to dissolve in the stomach, due to its relatively high water solubility, and may be absorbed via the gastric-intestinal tract.

Details on distribution in tissues:

When bioavailable, after e. g. ingestion or penetration of skin, the test item is likely to be metabolised and parent compound and degradation products are expected to easily distribute via systemic circulation.
Metabolism may transform the test item into even more polar degradation products. Likely pathways are reactions such as cytochrome P-450- dependent monooxygenase enzyme mediated N-oxidation. Parent compound and metabolites formed in phase I metabolic reactions may be rendered more polar by phase II metabolism in subsequent steps. The parent compound or possible metabolites may undergo conjugation (e. g. with glutamine), before being excreted in bile.
It is unlikely that the test item is metabolised to more reactive (toxic) products. This assumption is supported by results obtained in oral and dermal toxicity studies and two in vitro tests. In acute and subacute in vivo studies toxicity was low. In an Ames test and a chromosome aberration assay no significant increase in toxicity was noted in the presence of a rodent microsomal S9 -fraction, when compared to incubation without S9 -fraction. Together, this data indicates that formation of reactive metabolites is rather unlikely.
Based on the compound's structure and associated physical-chemical characteristics, bioaccumulation is not likely to occur. This is supported by the calculated bioconcentration factor of log BFC = 1.20 (US EPA Epiwin v.3.12). When bioavailable, the substance or its metabolites are expected to be well distributed throughout the body fluids and rapidly excreted via urine (non-conjugated forms) or via faces (high molecular weight conjugated forms).

Details on excretion:

Based on molecular weight and water solubility, the substance will most likely be excreted via urine and faeces.

Metabolites identified:

no

Conclusions:

The test item can be assumed to be absorbed by the oral and dermal routes of exposure.
In the toxicokinetic report it was stated, that further, irritation and corrosion properties of the substance may produce skin damage and thus enhance penetration. However, based on the available reliable in vivo skin irritation test according to OECD 404 (section 5.3.1.1 of the CSR), no irritation and corrosion properties will be expected for the test item.

Description of key information

The test item is solid at room temperature with a molecular weight of 192.65 g/mol. The partition coefficient (log Kow = 1.90) was determined using the HPLC method. The substances water solubility was determined to be 3.11 g/l.

 

1.       The test item can be assumed to be absorbed by the oral and dermal routes of exposure (as worst case an absorption rate of 100% for all routes is considered)

2.       There is no evidence of the formation of reactive or toxic metabolites.  

3.       The test item is not likely to bioaccumulate in adipose tissue, lungs, bone or stratum corneum based on the compound's structure and associated physical-chemical characteristics

4.       The test is expected to be excreted rapidly via urine (non-conjugated forms) or via faces (high molecular weight conjugated forms).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100