Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: toxicokinetic assessment
Adequacy of study:
key study
Study period:
April - December 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetic assessment by a certified toxicologist

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: ECB EU Technical Guidance Document on Risk Assessment, 2003
Qualifier:
according to
Guideline:
other: Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Main ADME results
Type:
absorption
Results:
For risk assessment purposes: oral absorption 100%, inhalation absorption 100% and dermal absorption 100%

Any other information on results incl. tables

TOXICOKINETIC ASSESSMENT

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration). The substance (NBDI) is insoluble in water, and reacts slowly with water. Therefore, passive diffusion will be limited. In addition, ionization of NBDI will impair the uptake since compounds need to pass the lipid membranes in the gastrointestinal wall. The relatively low molecular weight (206.24) of the substance however indicates that uptake can take place through aqueous pores. It is likely that uptake will be enhanced by local damage caused by the irritating properties of the substance. Overall, it is likely that NBDI is absorbed from the gastro-intestinal tract. For risk assessment purposes oral absorption of NBDI is set at 100%, due to the irritating properties of the substance, leading to potentially damaged gastrointestinal wall. The results of the toxicity studies do not provide reasons to deviate from this proposed oral absorption factor.

Once absorbed, distribution of the substance throughout the body is expected based on its relatively low molecular weight. Absorbed NBDI might undergo conjugation. The conjugates will either be excreted via the bile (high molecular weight compounds) or the urine (low molecular weight compounds).

The low vapour pressure (0.02076 Pa) and high boiling point indicates that is not likely that NBDI will reach the nasopharyncheal region or subsequently the tracheo/bronchial/pulmonary region. However, if the substance reaches the tracheobronchial region, it is likely to be absorbed through the aqueous pores due to the low molecular weight (206.24). In addition, the reactivity of NBDI with water is favourable for absorption. For risk assessment purposes the inhalation absorption of NBDI is set at 100%. The results of the toxicity studies do not provide reasons to deviate from this proposed dermal absorption factor.

NBDI, being a liquid, has the potential to partition from the stratum corneum into the epidermis. Since the substance reacts with water and has irritating properties, significant dermal uptake is likely due to damaged skin. As the data are insufficient to meet the criteria for 10% dermal absorption as given in Endpoint specific Guidance (MW> 500 and log Pow <-1 or >4), 100% dermal absorption of NBDI is proposed for risk assessment purposes.

 

Applicant's summary and conclusion

Conclusions:
For risk assessment purposes: oral absorption 100%, inhalation absorption 100% and dermal absorption 100%.