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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 December 1992 - 12 january 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Qualifier:
according to guideline
Guideline:
other: Japanese MAFF 59 NohSan No. 4200
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrahydrofurfuryl alcohol
EC Number:
202-625-6
EC Name:
Tetrahydrofurfuryl alcohol
Cas Number:
97-99-4
Molecular formula:
C5H10O2
IUPAC Name:
tetrahydrofuran-2-ylmethanol
Details on test material:
- Name of test material (as cited in study report): THFA (tetrahydrofurfuryl alcohol)

- Physical state: Clear liquid

- Storage condition of test material: Selected container protected from light at ambient temperature.

Test animals

Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Michigan
- Age at study initiation: Young adult
- Weight at study initiation: 217 to 283 grams
- Fasting period before study:
- Housing: Individual suspended wire mesh cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 28-62
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure chamber volume: Animals were exposed to test vapour in a 100 litre plexiglass whole body inhalation chamber.
- Method of holding animals in test chamber: The animals were housed in wire mesh cages during exposure; cage position was arbitrarily assigned.
- Source and rate of air: A stainless steel J-tube vapour generator was supplied with filtered, compressed air that was heated to ca. 93°C (200°F). An infusion pump was set to deliver test material at ca. 0.68 ml/min.
- System of generating particulates/aerosols: Sufficient test material was dispensed into a aluminium foil wrapped Erlenmeyer flask prior to atmosphere generation. The flask was maintained on a stir plate for the duration of the exposure to ensure even distribution of the test material. Fifty millilitre glass syringes were filled from this flask as needed.
- Method of particle size determination:
- Treatment of exhaust air: the air was drawn through an activated carbon bed, a HEPA filter and a water-spray fume scrubber
- Temperature, humidity, pressure in air chamber: A solomat probe and transmitter was used to monitor temperature and relative humidity.

TEST ATMOSPHERE
- Brief description of analytical method used: The test material was analyzed by infrared spectrometry with a gas analyzer. Atmosphere concentration was determined by by recording and reading an infrared absorbance value at a given time and entering this valve into the linear regression routine to determine the concentration of the test atmosphere in ppm.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Saturated vapour with a mean concentration of 751 ppm
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously for mortality and clinical signs during exposure, at approximately 1 hour after completion of exposure on day 0 and twice daily thereafter for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 751 ppm
Based on:
other: mean value for saturated vapour
Remarks on result:
other: Calculated by the reviewer to be equivalent to 3.1 mg/l
Mortality:
There were no deaths during the study.
Clinical signs:
other: Eight of the ten rats assumed a prostrate position during exposure and one of these animals had lacrimation from both eyes. At one hour after completion of exposure, 4/10 rats had wet yellow matting of the urogenital area and the entire dorsel surface was
Body weight:
Eight of ten rats lost 1 to 13 grams (less than 1% to ca. 5%) of body weight from the day of exposure (day 0) to day 3 (maximum individual loss of 5%). All but two females had recovered to exceed their initial body weight by day 14. There were no other remarkable weight changes during the study.
Gross pathology:
An enlarged lymph node and mottled areas in all lobes of the lungs were noted for one animal each. There were no changes observed for all other tissues at the terminal necropsy.
Other findings:
None reported.

Any other information on results incl. tables

751 ppm x MW 102.13

-------------------------

24.45

=

3136.99 mg/m3

----------------

1000

= 3.1 mg/l

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An LC50 value of >751 ppm (equivalent to >3.1 mg/l) was found in a reliable study, conducted according to the appropriate OECD guideline and in compliance with GLP.
Executive summary:

There were no deaths or remarkable body weight changes during the study. Transitory slight body weight losses and inhibition of body weight gain were observed, however, no remarkable effects associated with these changes were observed with regard to the general health of the rats.

The majority of the clinical findings were observed on the day of exposure. Eight of ten rats were prostrated during the exposure and this was considered to be a test material related effect. The ataxia, lacrimation, wet yellow urogenital staining and hypoactivity observed during exposure or at one hour post-exposure were also potentially related to the test material. Other clinical findings noted at low incidence included exophthalmia, dried red material around the nose or eyes and salivation. There were no significant clinical signs after day 1 and for the remainder of the study.

At the terminal necropsy, there were no test material related findings. Although one rat had mottled lungs, this finding is often spontaneous in rats and its occurrence in only one of ten animals is not indicative of a test material related effects.

The LC50 of THFA was found to be >751 ppm (equivalent to 3.1 mg/l) when male and female rats were exposed for a single four hour period under the conditions of this study.

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