Furfuryl alcohol

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

6 September 2006 (study initiiated), 6-15 August 2006 (experimental work completed)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline, human in-vitro study, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Study type:

other: investigation of in vitro metabolism in human nasal tissue

Endpoint addressed:

basic toxicokinetics

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The in-vitro metabolism of furfuryl alcohol was investigated in human nasal tissue.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Furfuryl alcohol

EC Number:

202-626-1

EC Name:

Furfuryl alcohol

Cas Number:

98-00-0

Molecular formula:

C5H6O2

IUPAC Name:

(furan-2-yl)methanol

Details on test material:

- Name of test material (as cited in study report): furfuryl alcohol
- Physical state: colourless liquid
- Analytical purity: 99.2%
- Source: Transfurans Chemicals BVBA, B-2440 Geel, Belgium
- Lot/batch No.: 060306PBP-A
- Storage condition of test material: in the dark at 4°C

Method

Type of population:

other: tissue from patients undergoing medical procedures

Subjects:

Human nasal tissue consisted of nasal turbinates collected from 10 patients undergoing turbinectomy and septorhinoplasty procedures.

Ethical approval:

confirmed, but no further information available

Route of exposure:

other: in vitro exposure to human tissue

Reason of exposure:

other: In-vitro research study

Details on exposure:

Human nasal microsomes were incubated with 20mM furfuryl alcohol for 60 minutes.

Results and discussion

Clinical signs:

Not applicable

Outcome of incidence:

The biological oxidation products produced by liver microsomes and the chemical oxidation products of furfuryl alcohol had comparable retention times. The metabolite was not detected when furfuryl alcohol was incubated with human nasal tissues (see figure below). The glutathione S-transferase activity of the nasal tissue was consistent with published values for respiratory nasal tissue (124 nmol/min/mg protein).

Applicant's summary and conclusion

Conclusions:

In contrast to rat and mouse nasal tissue, the in vitro metabolism of furfuryl alcohol in human nasal tissue gave no detectable oxidation products using the methodology described.

Executive summary:

A chemical oxidation product of furfuryl alcohol was generated by incubating furfuryl alcohol with m-chloroperoxybenzoic acid (mCPBA). The reaction products were trapped using semicarbazide and analysed by HPLC. The product formed by the biological oxidation of furfuryl alcohol in the rat liver microsomal incubations was found to have a comparable peak shape and retention time to that generated by the chemical oxidation of furfuryl alcohol. This product appears to be the same metabolite as identified in the previous research report (Mainwaring 2004). The samples were further analysed by LC/MS. However, the total ion current trace was weak and the response insufficient to give a mass spectrum.

This metabolite was not present in the incubation of furfuryl alcohol by human nasal tissue at levels above that of the negative controls.

In order to determine the viability of the tissue, a glutathione S-transferase assay was carried out using the cytosolic fraction of the tissue (there was insufficient microsomal protein left to determine any p450 reactions). The result of which demonstrated that the glutathione S-transferase activity is consistent with published data for respiratory nasal tissue at 124 nmol/min/mg protein (Banger et al 1993).