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EC number: 202-626-1 | CAS number: 98-00-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 31 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 3
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 143 mg/m³
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- Overall assessment factor (AF):
- 6
- Modified dose descriptor starting point:
- NOAEC
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 1
- Dose descriptor:
- LOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 1
- Dose descriptor starting point:
- LOAEC
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 12
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
Proposals for DNELs have been made following current ECHA guidance but also referring to the ECETOC Technical Report No .110 issued in October 2010: "Guidance on Assessment Factors to Derive a DNEL". In particular, based on the justifications provided in the report, an intraspecies assessment factor of 3 is used for workers.
HAZARD VIA INHALATION ROUTE
Systemic effects
Long-term exposure
The potential of a substance to cause long-term systemic effects can be judged based on the results of repeated dose toxicity and reproductive (fertility, developmental) testing.
For furfuryl alcohol, the following NOAECs are presented in the IUCLID dossier. For oral dosing these are based on data for the proximate metabolite, furfural (2-furaldehyde):
Oral:
sub-chronic effects: rat 13 wk NOAEL = 53 mg/kg bw/d
developmental toxicity: rat 13 wk NOAEL = 100 mg/kg bw/d
Inhalation:
sub-chronic effects: rat 14 wk NOAEC = 64 mg/m3
sub-chronic effects: mouse 14 wk NOAEC = 128 mg/m3
chronic effects: rat NOAEC = 32 mg/m3
chronic effects: mouse NOAEC = 32 mg/m3
The inhalation NOAEC in rats relates to effects (lower body weight and poorer survival) which are considered to be secondary consequences of the nasal irritation/tumours and in the mouse kidney damage which is considered to be exacerbation of an age-related phenomenon). Since there are no target organ effects in the 14 wk inhalation studies it is concluded that the DNEL for repeat dose exposure local effects will be protective for systemic effects.
The systemic NOAEL of 53 mg/kg bw/d will be referenced from the furfural study and an inhalation and dermal DNELs derived for systemic effects. The rationale is that, even though the NOAEC could be taken from the 14 wk inhalation studies, the doses were not sufficient to administer a systemic dose of 53 mg/kg bw/d i. e. the systemic dose resulting from 64 mg/m3is 16.5 mg/kg bw/d. The local effects reported, preclude the ability to carry out a repeat dose inhalation study at a dose which would produce systemic toxicity (i. e. liver toxicity).
Dose descriptor
In sub-chronic studies the NOAEL for systemic effects for the proximate metabolite, furfural, was 53 mg/kg bw/d in the rat.
Modification of dose descriptor
Convert the rat oral NOAEL (mg/kg bw/d) into a human inhalation NOAEC (mg/m3) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.3).
It is assumed that uptake of furfuryl alcohol after ingestion is 90% and after inhalation exposure, is 100%.
NOAECinhalation =Oral NOAEL x [1/ sRVrat[1]] x [ABSoral-rat/ABSinhal-human] x [sRVhuman/wRV]
NOAECinhalation =53 x [1/0.343] x [90/100] x [6.7/10]
= 93 mg/m3
[1] 8 hour value calculated from TGD Table R.8-17 values (as per guidance Appx R.8-2, example B.4) – sRV for rat (mean male/female) is 1.43 L/min/kg bw = 0.343 m3/kg bw for 8 hours (same duration of exposure as worker)
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
1 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
3 |
default AF for workers (ECETOC) |
Differences in duration of exposure |
1 |
normally a factor 2 is applied for extrapolation of subchronic to chronic exposure. However, given the results of the oral sub-chronic and chronic gavage study for furfural, no effect of exposure duration was found on the NOAEL and the effects observed. Therefore, no correction for differences between experimental conditions and exposure pattern of the worker is made (EC RAR, 2008) |
Dose response and endpoint specific/ severity issues |
1 |
default AF; clear NOAEC |
Quality of database |
1 |
default; GLP-compliant guideline study; additional factor not appropriate for as furfural is the proximate metabolite |
Overall AF |
3 |
|
DNELl-t inhal = 93 mg/m3/ 3
= 31 mg/m3
Acute/short term exposure
A DNEL for acute toxicity should be derived if an acute hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. These “peaks” are normally associated with inhalation exposure but are less common for skin contact and ingestion (TGD Guidance Appendix R.8-8). Furfuryl alcohol is classified for acute oral, dermal and inhalation toxicity. Acute hazard via the oral route is not relevant for workers. Hence an acute DNEL will be considered for the dermal and inhalation routes only.
Dose descriptor
The acute inhalation NOAEC for furfuryl alcohol in the rat (4 hr exposure) is 510 mg/m3.
Modification of dose descriptor
Initial modification of NOAEC of 510 mg/m3for light work (6.7 m3/ 10 m3) gives 340 mg/m3.
Adjust for duration only applying Haber’s law to derive the equivalent 15 min exposure:
(Ct=6)3x 4 = (Ct=0.25)3x 0.25
(Ct=0.25)3 = (340)3x 16
Ct=0.25 = 857 mg/m3
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
1 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
3 |
default workers (ECETOC) |
Differences in duration of exposure |
1 |
default AF |
Dose response and endpoint specific/ severity issues |
2 |
NOAEC from an acute study |
Quality of database |
1 |
Recent, GLP study |
Overall AF |
6 |
|
Inhalation DNELacute = 857 mg/m3/ 6
= 143 mg/m3
Local effects
Long term exposure
After chronic exposure, extensive non-neoplastic alterations in the respiratory and olfactory epithelia and hyperplastic Bowman’s glands were observed in both rats and mice (NTP, 1999). Sustained extensive chronic damage was necessary for tumour development and the NTP (1999) study report notes that the hyperplasia and squamous cell metaplasia in the rat represent conversion of highly specialised nasal tissue into more resistant types of epithelium, representing an adaptive response to chronic irritation. Based on these observations, furfuryl alcohol is considered to have respiratory irritating properties.
In humans it appears that furfuryl alcohol in combination with dust and formaldehyde or other chemicals, or exposure to various fumes and vapour might cause slight irritation and or acute restrictiveness of the lungs. However, a direct correlation with furfuryl alcohol exposure levels could not be clearly established since, in these studies, humans were exposed to mixtures and/or reactions products and not to furfuryl alcohol alone.
In most European countries, a national OEL of 5 or 2 ppm has been established for exposure to furfuryl alcohol on the workplace. In the present dossier on furfuryl alcohol, the limit value of 2 ppm is considered for risk assessment purposes. As discussed above, in repeated dose inhalation toxicity studies in rat, local effects on the nasal epithelium have been reported. These local effects have warranted classification of furfuryl alcohol under DSD as "irritating for the respiratory system" (Xi, R37). However, these irritating local effects on the nasal epithelium after repeated exposure have not been reported in the workplace over the 60 plus years that furfural alcohol has been manufactured and used. To confirm this, a statement ("no nasal irritation has been reported in workers exposed to furfuryl alcohol in a plant which could be attributed to fufuryl acohol") from a production plant is available (see attachment). Based on the absence of adverse effects reported in workers at the OEL of 2 ppm, equivalent to 8 mg/m3, this limit value is considered as a realistic limit value for assessment of safe use.
Dose descriptor
In chronic studies the reported LOAEC for local effects was 8 mg/m3. However, as relates to DNEL derivation, this LOAEC is actually regarded as a NOAEC (see justification under Section 5.3.4 of the CSR).
Modification of dose descriptor
No modification since this is a local effect.
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
1 |
Local irritant property induced by an elevated concentration of furfuryl alcohol with little if any difference in toxicodynamic/toxicokinetic effect across species Supporting this position is that there is comparability of effects between rats and mice in the NTP study, with no clear species difference in response at the lowest dose. Residual AF of 2.5 is not applicable since this is a physical effect at the site of entry and this is supported by the fact that there are no adverse effects reported in lower respiratory tract/lungs, at any dose level. In addition, metabolism could be argued to be not implicated since an NOAEC for the proximate metabolite, furfural, has been established at 8 mg/m3(28 day study [2]) with reported LOAEC of 20 mg/m3(furfural RAR, 2008). |
Intraspecies differences |
1 |
local irritant property induced by an elevated concentration of furfuryl alcohol with little if any difference in toxicodynamic/toxicokinetic effect within species |
Differences in duration of exposure |
1 |
Local effect, not relevant |
Dose response and endpoint specific/ severity issues |
1 |
‘NOAEC’ (see rationale in main text, CSR section 5.8.3) |
Quality of database |
1 |
Default AF |
Overall AF |
1 |
|
[2] Reference to the NOAEC is from a more recent study (Staal et al., 2008).
DNELl-t inhal = 8 mg/m3
Acute/short-term exposure
Corrosive and irritant effects on the skin are local, concentration-dependent phenomena. No dose/response information can be derived from data available for furfuryl alcohol and a DNEL cannot therefore be determined. It is proposed that furfuryl alcohol should be classified as irritating to the respiratory tract hence appropriate RMM and OCs should be employed.
HAZARD VIA DERMAL ROUTE
Systemic effects
Long term exposure
Dose descriptor
In sub-chronic studies the NOAEL for systemic effects for the proximate metabolite, furfural, was in 53 mg/kg bw/d in the rat.
Modification of dose descriptor
Convert the rat oral NOAEL (mg/kg bw/d) into a human dermal NOAEL (mg/kg bw/d) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.5).
It is assumed that uptake of furfuryl alcohol after ingestion is 90% and after dermal exposure, is 100%.
correctedDermal NOAEL = NOAELoralx [ABSoral-rat/ABSdermal-human]
correctedDermal NOAEL = 53 x [90/100] = 47.7 mg/kg bwt/d
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
4 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
3 |
default AF for workers (ECETOC) |
Differences in duration of exposure |
1 |
normally a factor 2 is applied for extrapolation of subchronic to chronic exposure. However, given the results of the oral sub-chronic and chronic gavage study for furfural, no effect of exposure duration was found on the NOAEL and the effects observed. Therefore, no correction for differences between experimental conditions and exposure pattern of the worker is made (EC RAR, 2008). |
Dose response and endpoint specific/ severity issues |
1 |
default AF; clear NOAEL |
Quality of database |
1 |
default; GLP-compliant guideline study; additional factor not appropriate for as furfural is the proximate metabolite |
Overall AF |
12 |
|
DNELl-t dermal = 47.7 mg/kg bw/d / 12
= 4.0 mg/kg bw/d
Acute toxicity
The available acute dermal data, although regarded as sufficient for classification purposes, is not considered suitable for quantitative, DNEL determination. It is proposed that the long-term dermal DNEL for systemic effects is, by default, sufficiently protective for acute effects (see below).
Local effects
Long term exposure
No information is available to characterise the repeated local effects of furfuryl alcohol on the skin, while route-to-route extrapolation (respiratory tract to skin) is not appropriate. However, risk management measures and other occupational controls are designed to limit skin irritation will also protect against long term local skin effects.
Acute/short term exposure
Corrosive and irritant effects on the skin are local, concentration-dependent phenomena. No dose/response information can be derived from data available for furfuryl alcohol and a DNEL cannot therefore be determined. It is proposed that furfuryl alcohol should be classified as irritating to skin hence appropriate RMM and OCs should be employed.
HAZARD FOR THE EYES
Local effects
Furfuryl alcohol is classified as an eye irritant (CLD Category 2 H319). No dose response information can be derived and therefore it is concluded to be of low hazard (ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation).
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 9.3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 5
- Modified dose descriptor starting point:
- NOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 128.5 mg/m³
- Most sensitive endpoint:
- acute toxicity
DNEL related information
- Overall assessment factor (AF):
- 10
- Modified dose descriptor starting point:
- NOAEC
Local effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 1
- Dose descriptor:
- LOAEC
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 1
- Dose descriptor starting point:
- LOAEC
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEL
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.4 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 20
- Modified dose descriptor starting point:
- NOAEL
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
Proposals for DNELs have been made following current ECHA guidance but also referring to the ECETOC Technical Report No .110 issued in October 2010: "Guidance on Assessment Factors to Derive a DNEL". In particular, based on the justifications provided in the report, an intraspecies assessment factor of 5 is used for the general population.
HAZARD VIA INHALATION ROUTE
Systemic effects
Long-term exposure
The potential of a substance to cause long-term systemic effects can be judged based on the results of repeated dose toxicity and reproductive (fertility, developmental) testing.
For furfuryl alcohol, the following NOAECs are presented in the IUCLID dossier. For oral dosing these are based on data for the proximate metabolite, furfural (2-furaldehyde):
Oral:
sub-chronic effects: rat 13 wk NOAEL = 53 mg/kg bw/d
developmental toxicity: rat 13 wk NOAEL = 100 mg/kg bw/d
Inhalation:
sub-chronic effects: rat 14 wk NOAEC = 64 mg/m3
sub-chronic effects: mouse 14 wk NOAEC = 128 mg/m3
chronic effects: rat NOAEC = 32 mg/m3
chronic effects: mouse NOAEC = 32 mg/m3
The inhalation NOAEC in rats relates to effects (lower body weight and poorer survival) which are considered to be secondary consequences of the nasal irritation/tumours and in the mouse kidney damage which is considered to be exacerbation of an age-related phenomenon). Since there are no target organ effects in the 14 wk inhalation studies it is concluded that the DNEL for repeat dose exposure local effects will be protective for systemic effects.
The systemic NOAEL of 53 mg/kg bw/d will be referenced from the furfural study and an inhalation and dermal DNELs derived for systemic effects. The rationale is that, even though the NOAEC could be taken from the 14 wk inhalation studies, the doses were not sufficient to administer a systemic dose of 53 mg/kg bw/d i. e. the systemic dose resulting from 64 mg/m3is 16.5 mg/kg bw/d. The local effects reported, preclude the ability to carry out a repeat dose inhalation study at a dose which would produce systemic toxicity (i. e. liver toxicity).
Dose descriptor
In sub-chronic studies the NOAEL for systemic effects for the proximate metabolite, furfural, was 53 mg/kg bw/d in the rat.
Modification of dose descriptor
Convert the rat oral NOAEL (mg/kg bw/d) into a human inhalation NOAEC (mg/m3) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.3).
It is assumed that uptake of furfuryl alcohol after ingestion is 90% and after inhalation exposure, is 100%.
NOAECinhalation =Oral NOAEL x [1/ sRVrat[1]] x [ABSoral-rat/ABSinhal-human] x [sRVhuman/wRV]
= 53 x [1/1.03] x [90/100]
= 46.3 mg/m3
[1] 24 hour value calculated from TGD Table R.8-17 values (as per guidance Appx R.8-2, example B.4) – sRV for rat (mean male/female) is 1.43 L/min/kg bw = 1.03 m3/kg bw for 24 hours (same duration of exposure as worker)
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
1 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
5 |
default AF for general population (ECETOC) |
Differences in duration of exposure |
1 |
normally a factor 2 is applied for extrapolation of subchronic to chronic exposure. However, given the results of the oral sub-chronic and chronic gavage study for furfural, no effect of exposure duration was found on the NOAEL and the effects observed. Therefore, no correction for differences between experimental conditions and exposure pattern of the worker is made (EC RAR, 2008) |
Dose response and endpoint specific/ severity issues |
1 |
default AF; clear NOAEC |
Quality of database |
1 |
default; GLP-compliant guideline study; additional factor not appropriate for as furfural is the proximate metabolite |
Overall AF |
5 |
|
DNELl-t inhal = 46.3 mg/m3/ 5
= 9.3 mg/m3
Acute/short term exposure
A DNEL for acute toxicity should be derived if an acute hazard leading to acute toxicity (e.g. C&L) has been identified and there is a potential for high peak exposures. These “peaks” are normally associated with inhalation exposure but are less common for skin contact and ingestion (TGD Guidance Appendix R.8-8). Furfuryl alcohol is classified for acute inhalation toxicity. Hence an acute DNEL is considered .
Dose descriptor
The acute inhalation NOAEC for furfuryl alcohol in the rat (4 hr exposure) of 510 mg/m3.
Modification of dose descriptor
Adjust for duration only applying Haber’s law to derive the equivalent 15 min exposure:
(Ct=4)3x 4 = (Ct=0.25)3x 0.25
(Ct=0.25)3` = (510)3x 16
Ct=0.25 = 1285 mg/m3
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
1 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
5 |
default general population (ECETOC) |
Differences in duration of exposure |
1 |
default AF |
Dose response and endpoint specific/ severity issues |
2 |
NOAEC from an acute study |
Quality of database |
1 |
Recent, GLP study |
Overall AF |
10 |
|
DNELacute = 1285 mg/m3/ 10
= 128.5 mg/m3
Local effects
Long term exposure
After chronic exposure, extensive non-neoplastic alterations in the respiratory and olfactory epithelia and hyperplastic Bowman’s glands were observed in both rats and mice (NTP, 1999). Sustained extensive chronic damage was necessary for tumour development and the NTP (1999) study report notes that the hyperplasia and squamous cell metaplasia in the rat represent conversion of highly specialised nasal tissue into more resistant types of epithelium, representing an adaptive response to chronic irritation. Based on these observations, furfuryl alcohol is considered to have respiratory irritating properties.
In humans it appears that furfuryl alcohol in combination with dust and formaldehyde or other chemicals, or exposure to various fumes and vapour might cause slight irritation and or acute restrictiveness of the lungs. However, a direct correlation with furfuryl alcohol exposure levels could not be clearly established since, in these studies, humans were exposed to mixtures and/or reactions products and not to furfuryl alcohol alone.
In most European countries, a national OEL of 5 or 2 ppm has been established for exposure to furfuryl alcohol on the workplace. In the present dossier on furfuryl alcohol, the limit value of 2 ppm is considered for risk assessment purposes. As discussed above, in repeated dose inhalation toxicity studies in rat, local effects on the nasal epithelium have been reported. These local effects have warranted classification of furfuryl alcohol under DSD as "irritating for the respiratory system" (Xi, R37). However, these irritating local effects on the nasal epithelium after repeated exposure have not been reported in the workplace over the 60 years and more that furfural alcohol is manufactured and used. To confirm this, a statement ("no nasal irritation has been reported in workers exposed to furfuryl alcohol in a plant which could be attributed to fufuryl acohol") from a production plant is available (see attachment). Based on the absence of adverse effects reported in workers at the OEL of 2 ppm, equivalent to 8 mg/m3, this limit value is considered as a realistic limit value for assessment of safe use.
Dose descriptor
In chronic studies the reported LOAEC for local effects was 8 mg/m3. However, as relates to DNEL derivation, this LOAEC is actually regarded as a NOAEC (see justification under Section 5.3.4 of the CSR).
Modification of dose descriptor
No modification since this is a local effect.
Assessment factors
Uncertainty |
AF |
Justification |
Interspecies differences |
1 |
Local irritant property induced by an elevated concentration of furfuryl alcohol with little if any difference in toxicodynamic/toxicokinetic effect across species Supporting this position is that there is comparability of effects between rats and mice in the NTP study, with no clear species difference in response at the lowest dose. Residual AF of 2.5 is not applicable since this is a physical effect at the site of entry and this is supported by the fact that there are no adverse effects reported in lower respiratory tract/lungs, at any dose level. In addition, metabolism could be argued to be not implicated since an NOAEC for the proximate metabolite, furfural, has been established at 8 mg/m3(28 day study [2]) with reported LOAEC of 20 mg/m3(furfural RAR, 2008). |
Intraspecies differences |
1 |
local irritant property induced by an elevated concentration of furfuryl alcohol with little if any difference in toxicodynamic/toxicokinetic effect within species |
Differences in duration of exposure |
1 |
Local effect, not relevant |
Dose response and endpoint specific/ severity issues |
1 |
‘NOAEC’ (see rationale in main text, CSR section 5.8.3) |
Quality of database |
1 |
Default AF |
Overall AF |
1 |
|
[2] Reference to the NOAEC is from a more recent study (Staal et al., 2008).
DNELl-t inhal = 8 mg/m3
Acute/short-term exposure
Corrosive and irritant effects on the skin are local, concentration-dependent phenomena. No dose/response information can be derived from data available for furfuryl alcohol and a DNEL cannot therefore be determined. It is proposed that furfuryl alcohol should be classified as irritating to the respiratory tract hence appropriate RMM and OCs should be employed.
HAZARD VIA DERMAL ROUTE
Systemic effects
Long term exposure
Dose descriptor
In sub-chronic studies the NOAEL for systemic effects for the proximate metabolite, furfural, was in 53 mg/kg bw/d in the rat.
Modification of dose descriptor
Convert the rat oral NOAEL (mg/kg bw/d) into a human dermal NOAEL (mg/kg bw/d) after adjusting for differences in uptake between the two routes of exposure (TGD, Appendix R.8-2, Example B.5).
It is assumed that uptake of furfuryl alcohol after ingestion is 90% and after dermal exposure, is 100%.
correctedDermal NOAEL = NOAELoralx [ABSoral-rat/ABSdermal-human]
correctedDermal NOAEL = 53 x [90/100] = 47.7 mg/kg bwt/d
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
4 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
5 |
default AF for general population (ECETOC) |
Differences in duration of exposure |
1 |
normally a factor 2 is applied for extrapolation of subchronic to chronic exposure. However, given the results of the oral sub-chronic and chronic gavage study for furfural, no effect of exposure duration was found on the NOAEL and the effects observed. Therefore, no correction for differences between experimental conditions and exposure pattern of the worker is made (EC RAR, 2008). |
Dose response and endpoint specific/ severity issues |
1 |
default AF; clear NOAEL |
Quality of database |
1 |
default; GLP-compliant guideline study; additional factor not appropriate for as furfural is the proximate metabolite |
Overall AF |
20 |
|
DNELl-t dermal = 47.7 mg/kg bw/d / 20
= 2.4 mg/kg bw/d
Acute toxicity
The available acute dermal data, although regarded as sufficient for classification purposes, is not considered suitable for quantitative, DNEL determination. It is proposed that the long-term dermal DNEL for systemic effects is, by default, sufficiently protective for acute effects (see below).
Local effects
Long term exposure
No information is available to characterise the repeated local effects of furfuryl alcohol on the skin, while route-to-route extrapolation (respiratory tract to skin) is not appropriate. However, classification and labelling are designed to limit skin irritation will also protect against long term local skin effects.
Acute/short term exposure
Corrosive and irritant effects on the skin are local, concentration-dependent phenomena. No dose/response information can be derived from data available for furfuryl alcohol and a DNEL cannot therefore be determined. It is proposed that furfuryl alcohol should be classified as irritating to skin hence appropriate RMM and OCs should be employed.
HAZARD VIA ORAL ROUTE
Systemic effects
Long term exposure
Dose descriptor
In sub-chronic studies the NOAEL for systemic effects for the proximate metabolite, furfural, was in 53 mg/kg bw/d in the rat.
Modification of dose descriptor
Adjustment for 90% absorption is proposed to 47.7 mg/kg bw/d
Assessment factors
Uncertainty |
AFs |
Justification |
Interspecies differences |
4 |
differences in metabolic rate no AF for remaining differences |
Intraspecies differences |
5 |
default AF for general population (ECETOC) |
Differences in duration of exposure |
1 |
normally a factor 2 is applied for extrapolation of subchronic to chronic exposure. However, given the results of the oral sub-chronic and chronic gavage study for furfural, no effect of exposure duration was found on the NOAEL and the effects observed. Therefore, no correction for differences between experimental conditions and exposure pattern of the worker is made (EC RAR, 2008) |
Dose response and endpoint specific/severity issues |
1 |
default AF; clear NOAEC |
Quality of database |
1 |
default; GLP-compliant guideline study; additional factor not appropriate for as furfural is the proximate metabolite |
Overall AF |
20 |
|
DNELl-t oral = 47.7 mg/kg bwt/d / 20
= 2.4 mg/kg bw/d
Acute/short term exposure
In the absence of specific dose response information for acute oral toxicity, the DNELl-t oral will be used for the acute DNEL.
HAZARD FOR THE EYES
Local effects
Furfuryl alcohol is classified as an eye irritant (CLD Category 2 H319). No dose response information can be derived and therefore it is concluded to be of low hazard (ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation).
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