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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
2 test groups
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Furfural technical, 100% nominal
- Substance type: Technical product
- Physical state: pale yellow liquid
- Analytical purity: 100% nominal
- Composition of test material, percentage of components: Furfural 99.8 wt % minimum, other ingredients 0.2 wt % maximum
- Purity test date: Not reported
- Lot/batch No.: 5210 (04/29/02)
- Expiration date of the lot/batch: Not determined
- Stability under test conditions: Stable at ambient and elevated temperatures
- Storage condition of test material: Not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals Inc., Boyertown, PA, USA
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 300-345g (males), 206-237g (females)
- Fasting period before study: no
- Housing: single housed in suspended stainless steel cages with mesh floors and litter paper beneath the cage.
- Diet : Purina Rodent Chow # 5012
- Water : Tap water ad libitum except during exposure.
- Acclimation period: 13 or 20 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-23°C
- Humidity: 32-69 %
- Air changes (per hr): Not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 28 April 2003 To: 19 May 2003

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber (Mini Nose-Only Inhalation Chamber, ADG Developments LTD).
- Exposure chamber volume: 6.7 L
- Method of holding animals in test chamber: individually in polycarbonate tubes.
- Source and rate of air: Filtered air was supplied at 30 psi by an air compressor to the spray atomization nozzle (average air flow 23.3 Lpm).
- Method of conditioning air: Dried, filtered compressed air was supplied (average air flow 2.3 Lpm).
- System of generating particulates/aerosols: Aerosolised using an atomiser and syringe pump. Compressed air was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet.
- Method of particle size determination: Anderson cascade impactor
- Treatment of exhaust air: Not reported
- Temperature, humidity in air chamber: 20-21°C, 35-40%

TEST ATMOSPHERE
- Brief description of analytical method used: Samples of chamber air were collected using two 125 mL gas bubblers in series, for 30 minutes at a flow rate of 4 Lpm, and analysed by GLC.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE - see Table 1
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.54 and 1.63 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed during and following exposure and then at least once daily for 14 days. Weighed prior to exposure and then on days 7 and 14 or after death.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross necropsy of decedents
Statistics:
Not performed

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.54 - < 1.63 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: 7/10 deaths at 1.63 mg/L
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 540 - < 1 630 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: equivalent dose. No deaths at 540 mg/m3, 7/10 deaths at 1630 mg/m3
Mortality:
Two males and all five females died following exposure to 1.63 mg/L furfural (of these, two males and two females died during exposure and the other 3 females died on day 1). There were no deaths following exposure to 0.54 mg/L furfural .
Clinical signs:
other: Clinical signs noted following exposure to 1.63 mg/L furfural technical included irregular respiration, dyspnea, hypoactivity and/or abnormal posture and three females died on day 1. The three surviving males exhibited similar clinical signs, but recovere
Body weight:
Surviving males exposed to 1.63 mg/L furfural technical and all rats exposed to 0.54 mg/L furfural technical gained weight on days 7 and 14.
Gross pathology:
Necropsy of the decedents revealed discoloration of the lungs and intestines, and oedema of the lungs.
No gross abnormalities were noted for the surviving animals at 1.63 mg/L and for all animals exposed to 0.54 mg/L necropsied at end of the 14-day observation period.

Any other information on results incl. tables

Table 1. Summary of test atmosphere concentrations and particle size data

Nominal concentration (mg/L)

2.27

3.60

Analysed concentration (mg/L)

0.54

1.63

Mass median aerodynamic diameter (µm)

2.3

2.3

Geometric standard deviation

1.94

1.94

 

Applicant's summary and conclusion

Conclusions:
The acute inhalation LC50 of furfural technical (100% nominal) is between 0.54 and 1.63 mg/L in male and female rats.
Executive summary:

In an acute inhalation toxicity study in rats, two groups of 5 male and 5 female rats were exposed, nose-only, to aerosols of furfural technical for 4 hours. The analysed concentrations of the test atmospheres were 0.54 and 1.63 mg/L and the mass median aerodynamic diameter was 2.2 µm for both atmospheres. Seven out of 10 animals died during and following exposure to 1.63 mg/L. There were no deaths following exposure to 0.54 mg/L and all rats survived the 14 day observation period. Clinical signs seen following exposure to 1.63 mg/L included irregular respiration, dyspnea, hypoactivity and/or abnormal posture. Reduced activity, seen within 1 hour of the end of exposure, was the only clinical sign seen at 0.54 mg/L. Necropsy of the decedents revealed discoloration of the lungs and intestines, and oedema of the lungs. There were no gross abnormalities in the surviving animals at 1.63 mg/L and for all animals exposed to 0.54 mg/L necropsied at end of the 14-day observation period.

The acute inhalation LC50 of furfural technical (100% nominal) is between 0.54 and 1.63 mg/L in male and female rats.