Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The work described was performed in compliance with UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1997 (SI 1997/654)). These Regulations are in accordance with GLP standards published as OECD Principles on Good Laboratory Practice (revised 1997, ENV/MC/CHEM(98)17); and are in accordance with, and implement, the requirements of Directives 87/18/EEC and 88/320/EEC.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Sponser's identification: Ethyl Tetrahydrofurfuryl ether
- Date received: 18 November 1998
- Description: Colourless Liquid
- Storage conditions: under nitrogen at room temperature in the dark

Data relating to identity, purity and stability of the test material are the responsibility of the sponser

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sprague Dawley Crl:CD®BR strain rat. Supplied by Charles River (Uk) Ltd, Margate, Kent.
- Age at study initiation: At the start of the study the animals were approx. eight to ten weeks old
- Weight at study initiation: Males weighed 333 to 347g, and females 240 to 271g.
- Acclimation period: at least five days.
- Animals were given a unique number within the study by ear punching and a number written on a colour coded cage card.
- Housing: In groups of five by sex in solid-floor polypropylene cages with stainless stell lids, furnished with softwood flakes (Datesand Ltd, Chesire, UK) Bedding routinely analysed and considered not to contain any contaminants that could be reasonably be expected to affect the purpose or integirty of the study.
- Diet: Free access to food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limtied, Witham, Essex, UK). Diet routinely analysed and considered not to contain any contaminants that could be reasonably be expected to affect the purpose or integirty of the study.
- Water: Free access ro mains drinking water. Drinking water routinely analysed and considered not to contain any contaminants that could be reasonably be expected to affect the purpose or integirty of the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): - Maintained within target ranges of 21 ± 2°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

The animals were retained in this accommodation at all times except during this exposure period.

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
nose only
Details on inhalation exposure:
- A vapour was produced from the test material by bubbling compressed air through two glass impingers conncected in series each containing 100ml of test material. The impingers were places in a water bath maintained at a temperature of 60°C. The resultant vapour was ducted into the top of the exposure chamber.

Compressed air was supplied by meand of an oil free compressor and was passed through a water trap and respiratory quality filters before it was introduced to the chamber.

The cylindrical exposure chamber had a volume of approx. 30 litres (dimensions: 28cm diameter x 50 cm high). The extract from the exposure chamber passed through an activated charcoal trap and was connected with a high effiency filter to a metered exhaust system. The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during the study, but chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animlas' breathing zone with a wide variety of test materials (Green J D et al, 1984).

Prior to the start of the study, test material atmospheres were generated within the exposure chamber. During characterisation period air flow settings, temperature settings and the sampling system were varied to achieve the optimum atmospheric concentrations. The maximum attainable vapour concentration, avoiding aerosol production, was considered to have been acheived. During this characterisation period two animals (one male and one female) were exposed to maximum attainable vapour concentration for approximately two hours to act as a sighting. no severe signs of toxicity were observed.

Concentrations:
Mean maximum attainable vapour concentration of 13.7mg/l.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes
Details on study design:
Exposure Procedure: Each rat was individually held in a tapered, polycarbomnate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring. Only the nose of each animal was exposed to the test atmosphere.

Following an appropriate equilibration period a single group of ten rats (five males and five females) were exposed to a vapour at the test material for a period of four hours. A target concentration of 20 mg/l was used for exposure but, since this was not achievable, the animals were exposed to the maximum attainable vapour concentration. No deaths occured and therefore no further levels were required.

Exposure Chamber Temperature and Relative Humidity: the temperature and relative humidity insisde the exposure chamber were measured by an electronic thermoometer/humidity meter (Kane-May Ltd., Welwyn Garden City, Hertfordshire, UK) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

Exposure Chamber Oxygen Concentrations: Oxygen Levelswithin the exposure chamber were measured by an electronic oxygen anlyser (Servomex (UK) Ltd, Crowborough, East Sussex) located in a sampling port in the animals' breathing zone during the exposure period. The test atmosphere was generated to contain at least 19% oxygen.

Exposure Chamber Atmosphere Concentration: The chamber concentration was sampled three minutes after the start of exposure and then at approximately hourly intervals during the exposure period.

The sampling procedure involved pumping one litre of the chamber atmosphere through a glass impinger containing 40ml of methanol. after sampling the dreschel head was flushed with a further 10ml of methanol to remove any deposits. This gave a 50ml sample to be submitted for chemical analysis.

The nominal chamber concentration was calulated as follows:

Nominal concentration (mg/l) = weight of test material used 9mg)/total air flow through chamber (l)

Results and discussion

Effect levels
Dose descriptor:
LC50
Effect level:
13.7 other: mg/l
Based on:
test mat.
Mortality:
No deaths occured in a group of 10 rats exposed to a mean maximum attainable vapour concentration of 13.7mg/l.
Clinical signs:
All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Any evidence of overt toxicity was recorded at each observation. Common abnormalities observed during the study included wet fur, hunched posture, pilo-erection, laboured respiration and increased or decreased respiratory rate. Incidents of ataxia, extreme lethargy, loss of righting reflex and red/brown staining around eyes, snouth and on the head were noted and there were isloated signs of occasional body tremors and tiptoe gait. All animals recovered to appear normal on Day 4 following exposure.
Body weight:
Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14
Other findings:
Necropsy: with the exception of 1 male and 1 female which showed dark foci on the lungs, no abnormalities were detected at necopsy.

Any other information on results incl. tables

Necropsy: At the end of the fourteen day observation period, the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full internal and external examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs or irritancy or local toxicty.

Evaluation of Data: Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, bodyweight changes, mortality and any other toxicological effects.

Using mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Applicant's summary and conclusion

Conclusions:
no deaths occured in a group of ten rats exposed to a mean maximum attainable vapour concentration of 13.7mg/l. It was therefore considered that the acute inhalation mediam lethal concentration (LC50) of the test material ETHYL TETRAHYDROFURFURYL ETHER, in the Sprague-Dawley CD strain rat, was greater than 13.7 mg/l.