Registration Dossier

Administrative data

Description of key information

The oral LD50 was determined to be 463 mg/kg.
The inhalation LC0 was determined to be 6 mg/l.
The dermal LD50 was determined to be >400 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP non-guideline, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
BASF internal standardized method: Two rabbits per dose exposed orally to the test substance. Necropsy performed on the animals that died.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Route of administration:
oral: unspecified
Vehicle:
other: Aqueous emulsion of Tragacanth
Doses:
0.4, 0.5, 1.0 mL/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
>= 0.5 - <= 1 mL/kg bw
Based on:
test mat.
Mortality:
- No mortality observed in animals exposed to 0.4 and 0.5 mL/kg.
- All animals exposed to 1 mL/kg died, within 24 hours after exposure.
Clinical signs:
- Loss of apetite observed in animals exposed to 1.0 mL/kg
- In one animal, exposed to 0.4 or 0.5 mL/kg, a temporary lack of appetite, convulsive trembling, apathy and diarrhea were observed.
Gross pathology:
At the necropsy a histologically detectable extensive submucosal bleeding of the stomach was observed, in one of the animals that died
Other findings:
- Histopathology: Kidney damage was observed
Interpretation of results:
harmful
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
463 mg/kg bw
Quality of whole database:
Four acute oral toxicity studies are available presented in four reports, with three species. One study is considered to be klimisch 4, because only a summary is available. All other studies are regarded as klimisch 2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study, non-GLP, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Principles of method if other than guideline:
10 Sprague-Dawley rats per sex per dose were exposed to 4.8 or 6.0 mg/L of the test substance for 4 hours by inhalation. After exposure, the animals were observed for 14 days.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wiga, Sulzfeld
- Weight at study initiation: 190 and 220 g, for females and males respectively
- Diet: ad libitum, Herilan MRH (H.Eggermann KG, Rinteln/Weser)
- Water: tap water ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Rate of air: 3 L/h
- Exposure chamber volume: 180 L

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
4.8 and 6 mg/L air
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
- Frequency body weight determination: before the study, 7 days after exposure and at the end of the study
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality observed.
Clinical signs:
- 4.8 mg/L: Eyelid closure
- 6.0 mg/L: Eyelid closure and slightly red nose area
Body weight:
There was no difference in the body weight gain between the control group and the experimental groups.
Gross pathology:
No effects observed.
Endpoint conclusion
Quality of whole database:
Nine acute inhalation toxicity studies are available presented in five reports, with five species. One study is considered to be klimisch 4, because only a summary is available. All other studies are regarded as klimisch 2. Two studies of them cannot be used for classificication because the exposure value is not presented, the results of the others are not sufficient for classification and labeling purposes.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline study, non-GLP, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment
Reference:
Composition 0
Principles of method if other than guideline:
BASF internal method
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: M.Gaukler, 6050 Offenbach
- Weight at study initiation: 2.69 and 2.74 kg, for females and males respectively
- Diet: ad libitum, Ssniff K standardiet for rabbits and guinea pigs (Intermast GmbH, Soest)
- Water: ad libitum
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: shaved back and flank (ca. 210 cm2)
- Type of wrap if used: aluminium foil, fixated with adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing: warm water or water/lutrol mixture. Dryed with pulp.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
400 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 8 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 400 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed.
Clinical signs:
Strong local irritation was observed in all exposed animals 24 hours after exposure. This remained until the end of the study and developed into scaling.
Gross pathology:
No effects observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Two acute dermal toxicity studies are available. One study is regarded to be klimisch 2 while the other is considered klimisch 4, because only a summary is available.

Additional information

Acute toxicity: oral

Four acute oral toxicity studies are performed with three different species. In all of these studies minimal information on the method of the study has been reported. In the first study (BASF 1959) rats were exposed to 2,5-dihydrofuran dissolved in an aqueous emulsion of Tragacanth. No pathological effects were observed. The LD50 was determined to be 0.9 cm3/kg, which is equivalent to 850 mg/kg bw. In the second study (EKCO 1963), rats were exposed to the undiluted substance. The LD50 was determined to be between 800 and 1600 mg/kg bw. Only a study summary was available for this study and therefore a klimisch score of 4 has been applied. In the third (BASF 1961, cats), and fourth study (BASF 1961, rabbits), animals were exposed to the substance dissolved in an aqueous emulsion of Tragacanth. Two cats per dose were exposed to 0.5, 1.0, 1.6 mL/kg, and two rabbits per dose were exposed to 0.4, 0.5, 1.0 mL/kg. No pathological effects were observed in cats, but submucosal bleeding of the stomach was observed in one rabbit that died. Based on the mortality the LD50 is between 1.0 and 1.6 mL/kg bw for cats and 0.5 and 1.0 mL/kg bw for rabbits. With a density of 0.927 g/mL, the LD50 in mg/kg bw would be 927 to 1480 mg/kg bw for cats and 463 to 927 mg/kg bw for rabbits. Although only a LD50-range is available, as a worst-case approach, the lowest value of the LD50-range obtained in the study with rabbits has been used: 463 mg/kg bw.

 

Acute toxicity: inhalation

Nine acute inhalation toxicity studies are performed with five different species. These were presented in five study reports.

In one report (BASF 1961) studies were performed with 5 different animals species (rat, mouse, rabbit, guinea pig and cat). In these studies animals were exposed to a vapour at concentrations of 1000 ppm (2 or 4 hours) and 10,000 ppm (6 hours). Of all animals exposed to 1000 ppm, only 2 out of 10 mice died. All rats, mice and guinea pigs, and 1 out of 2 rabbits exposed to 10,000 ppm for 4 hours died. All mice, no rats, 1 out of 2 rabbits and 1 out of 2 guinea pigs exposed to 10,000 ppm for 2 hours died. Cats were not exposed to 10,000 ppm.

In two other studies, rats were exposed to the saturated vapour of the test substance at different exposure times (BASF 1959 and BASF 1978,kli-dd). In the first study (BASF 1959) rats were exposed for 2, 8 or 30 minutes. No mortality was observed in rats exposed for 2 minutes, 4 out of 6 died exposed for 8 minutes, and all animals died exposed to 30 minutes. In the second study (BASF 1978 -kli-dd) rats were exposed for 3, 10 or 30 minutes. No mortality was observed in rats exposed for 3 minutes, 1 out of 6 died exposed for 10 minutes, and 4 out of 6 animals died exposed to 30 minutes. Concentrations to which animals were exposed in these studies were not presented, but based on a vapour pressure of 162.25 hPa, the concentration would be approximately 468 mg/L. Conversion of these concentration levels to a 4 -hour exposure time would not be reliable because of the short exposure times tested. Therefore, these data were not used for classification.

In another study (EKCO 1963), 3 rats per dose were exposed to 10.39 mg/L for 6 hours and 393.33 mg/L for 1 hour. No animals died exposed to 10.39 mg/L, and all animals exposed to 393.33 mg/L died. The type of inhalation exposure was not specified, but it is assumed that a vapour was used. This study has a klimisch rating of 4 and is therefore not used for the final classification.

In a different study (BASF 1978,kli-br) ten Sprague Dawley rats per sex per dose were exposed to 4.8 and 6 mg/L air for 4 hours. No mortality or pathological effects were observed. The LC50 was therefore determined to be higher than 6 mg/L air. This study was not used for classification, because the test concentrations were below the highest classification limit.

In conclusion, all data available are not sufficient for classification and labeling purposes.

Acute toxicity: dermal

Two acute dermal toxicity studies are performed with two different species. In the first study (BASF 1979), five Vienna White rabbits were dermally exposed to 400 mg/kg unchanged 2,5-dihydrofuran under occlusion for 24 hours. Strong local irritation was observed, but no mortality. The LD50 was therefore determined to be more than 400 mg/kg. In the second study (EKCO 1963) guinea pigs were exposed to 0.1 to 20.0 cc/kg of the unchanged substance. Necrosis, erythema and edema were observed. The LD50 was determined to be between 1 and 5 cc/kg. With a density of 0.927 g/mL, the LD50 would be between 925 and 4635 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Four acute oral toxicity studies are available, performed in three species. The study with the most sensitive species (rabbit) has been selected as key study.

Justification for selection of acute toxicity – inhalation endpoint
Nine acute inhalation toxicity studies are available, performed in five species. The most reliable study has been selected as key study. However none of the results available are sufficient for classification and labeling purposes.

Justification for selection of acute toxicity – dermal endpoint
Two acute dermal toxicity studies are available, performed in two species. The most reliable study was chosen as key study.

Justification for classification or non-classification

Based on an oral LD50 of 463 mg/kg bw 2,5-dihydrofuran has to be classified for Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn: R22: Harmful if swallowed in accordance with Directive 67/548/EEC (DSD).

The inhalation LC0 was determined to be 6 mg/L, classification for acute inhalation toxicity is therefore not possible in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Directive 67/548/EEC (DSD).

The dermal LD50 was determined to be higher than 400 mg/kg, classification for acute dermal toxicity is therefore not possible in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Directive 67/548/EEC (DSD).