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Toxicological information

Repeated dose toxicity: oral

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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

Referenceopen allclose all

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 Type:
other: citation in RAR (2008)
Title:
Unnamed
Year:
2000

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
no Functional Observation Battery
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 30, 60, 90, or 180 mg/kg bw/day
Basis:
nominal in diet
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..