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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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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:
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 recovered by Day 3, and appeared active and healthy for the remainder of the study.
Following exposure to 0.54 mg/L furfural technical, reduced activity was noted in three rats within 1 hour following exposure. Thereafter, there were no adverse clinical signs and all animals appeared active and healthy until scheduled termination.
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.