2-furaldehyde

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data extracted from EU RAR (2008). Original report could not be sourced, but widely cited in regulatory reviews.

Data source

Reference

Reference 1

Reference Type:

other: EU Risk Assessment Report

Title:

RISK ASSESSMENT REPORT 2-FURALDEHYDE (Furfural) CAS-No.: 98-01-1 EINECS-No.: 202-627-7

Author:

EU RAR

Year:

2008

Bibliographic source:

Risk Assessment: 2-furaldehyde – final report (final approved version February 2008).

Reference 2

Reference Type:

other: citation in RAR (2008)

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

no Functional Observation Battery

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

furfural

IUPAC Name:

furfural

Constituent 2

Reference substance name:

2-furaldehyde

EC Number:

202-627-7

EC Name:

2-furaldehyde

Cas Number:

98-01-1

Molecular formula:

C5H4O2

IUPAC Name:

2-furaldehyde

Details on test material:

The test material consisted of microencapsulated furfural in a carrier of maltodextrin and mixed sugars.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: microcapsules consisting of maltodextrin and mixed sugars

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

No data, but it was stated in the review that actual doses were derived from nominal doses by analysis of the food.

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Continuous in diet

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 30, 60, 90, or 180 mg/kg bw/day
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
Males: 0, 26, 53, 82, or 160 mg/kg; Females, 0, 28, 57, 86 or 170 mg/kg
Basis:
actual ingested

No. of animals per sex per dose:

10/sex/dose

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED
CLINICAL OBSERVATIONS: yes
- Time schedule: no data

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: no data
- Dose groups that were examined: high dose and controls

HAEMATOLOGY: Yes (parameters not specified)
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all

CLINICAL CHEMISTRY: Yes (parameters not specified)
- Time schedule for collection of blood: No data (presumably at termination)
- Animals fasted: No data
- How many animals: all

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (with measurements of organ weights; list of organs weighed not given)
HISTOPATHOLOGY: Yes (“extensive histological examination of a range of organs”)

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Ophthalmological findings:

no effects observed

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Details on results:

The full text of the Risk Assessment Report’s evaluation of this study is presented below:
“There were no clinical signs of toxicity, and body weights and food consumption were unaffected by treatment. The animals given the high dose showed no ophthalmoscopic changes when compared with controls. Some changes in clinical chemistry were seen. The haematological changes included a decreased red blood cell count in males dosed at 180 mg/kg bw per day and increased corpuscular volume and mean corpuscular haemoglobin in males dosed at 90 and 180 mg/kg bw per day. Females at the high dose showed decreased alkaline phosphatase activity, increased γ-glutamyltransferase activity, increased plasma concentration of albumin, and decreased plasma concentration of potassium. Males at the high dose showed decreased alanine aminotransferase activity, increased plasma concentration of albumin, and increased albumin:globulin ratio. Increased albumin:globulin ratios were also found in males at 30 and 90 mg/kg bw per day but not in those at 60 mg/kg bw per day.
At necropsy, the absolute and relative weights of the liver were increased in males at 180 mg/kg bw per day, but there were no gross pathological changes. Microscopic examination revealed changes in the liver in 5/10 males at 90 mg/kg bw per day and in 10/10 males at 180 mg/kg bw per day. The changes were found mainly in the perilobular region and were characterized by cells having less coarse cytoplasm, an increased occurrence of clumps of eosinophils, a less dense periphery, and more prominent nucleoli in the nucleus. The changes seen at 90 mg/kg bw per day were not severe, and those in rats at 180 mg/kg bw per day were slight with none being accompanied by signs of degeneration or necrosis. No changes were observed in the livers of females, and there were no signs of hepatotoxicity such as degeneration, necrosis, or inflammation. No bile-duct proliferation was seen. The NOAEL was 60 (i.e. 53) mg/kg bw per day.”

Effect levels

Dose descriptor:

NOAEL

Effect level:

53 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: haematological and microscopic liver changes in males at 82 and 160 mg/kg

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 13-week dietary toxicity study with furfural in rat, a NOAEL of 53 mg/kg bw/day was established based on microscopic liver changes and haematological changes in male rats at 82 mg/kg bw/day..