Registration Dossier

Administrative data

Description of key information

Repeated dose oral, inhalation and dermal toxicity studies with furfural in rats, mice or hamsters are available. Evidence of slight systemic toxicity was seen following oral exposure whilst following inhalation exposure the primary effect is irritation and tissue damage in the nasal region.  The NOAEC for nasal irritation was 8 mg/m3.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
53 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
320 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Additional information

The toxicity of furfural was reviewed and a final Risk Assessment Report published by the EU in 2008 (EU RAR, 2008).

Oral

No new oral studies have been identified. The key study identified for oral toxicity was a 13 week feeding study in rats (Jonker, 2000a, b). In this study haematological differences and minor microscopic liver changes were seen in males at 82 and 160 mg/kg. In females minor clinical chemistry changes were seen at 170 mg/kg (Jonker, 2000a, b). The lowest NOAEL was < 11 mg/kg bw/day in a 13 week gavage study (Irwin, 1990a) based on cytoplasmic vacuolation of hepatocytes in the centrilobular region in all males only at all dose levels. However, the design of this study was limited (it was a preliminary for a subsequent carcinogenicity study), would result in high peak exposures due to gavage dosing and used corn oil as vehicle, which is known to be associated with morphological liver changes. As higher dose levels were achieved in the dietary study and minor hepatocellular alterations were seen in males only with a clear NOAEL, the overall oral NOAEL of 53 mg/kg bw/day from the Jonker (2000a, b) study is used as the starting point for risk assessment.

Inhalation

Inhalation studies have been conducted in rats and hamsters. The key studies are considered to be 28 day inhalation studies in rats (Staal et al, 2008; Arts et al, 2004). In the earlier study a high incidence of mortality was seen following exposures of 640 and 1280 mg/m3 for 6 hours/day, 5 days/week. There was no evidence of systemic toxicity at lower concentrations giving a systemic NOAEC of 320 mg/m3. However, evidence of nasal irritation was seen at all exposure concentrations. In the later study the exposure concentrations were selected in order to determine a NOAEC for nasal irritation. At 20 mg/m3 respiratory epithelial hyperplasia and inflammatory cell infiltration was seen in both males and females at the end of the study and but only mononuclear cell infiltration in a single male following 4 weeks recovery. A clear NOAEC for local effects was established at 8 mg/m3.

Dermal

In a 28 day dermal toxicity study high mortality and adverse clinical signs were observed in both male and female rats dosed with 500 mg/kg/day. At 100 and 250 mg/kg/day no treatment-related effects were observed on body weight, body weight gain, food consumption, food efficiency, haematology, clinical chemistry or urinalysis parameters, ophthalmoscopic examination or on gross or histopathological examination (EPA, 2010). The systemic NOAEL is 250 mg/kg/day. There was no indication of dermal irritation giving a NOAEL for local effects of 1000 mg/kg/day.

The registrant does not have a letter of access to these data therefore to derive a DNEL long term for dermal exposure route to route extrapolation from the oral NOAEL is proposed. This NOAEL is clearly lower than those reported (EPA, 2010) following dermal exposure. Route to route extrapolation is therefore considered to be precautionary and protective of workers and consumers following dermal exposure to furfural.

Human data

During regular medical examinations of employees at the Jugotanin plant in Slovenia (Medicinski Center, 1989), none of the employees showed any evidence of adverse health effects that were considered to have been a consequence of daily contact with furfural.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

Following repeated oral, inhalation or dermal exposure there was no evidence of significant target organ toxicity at dose level below regulatory thresholds and no classification is warranted for this end-point.

Irritation of the respiratory system of rats and hamsters was seen after inhalation exposure. Based on these observations furfural is a respiratory irritant and is classified as follows: R37 “Irritating to respiratory system” according to Dir 67/548/EEC; H335 “May cause respiratory irritation” under Reg (EC) 1272/2008.