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Administrative data

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw
Acute inhalation toxicity: LD50 > 6.3 mg/L (maximum attainable vapour concentration)

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
Study period:
1996-05-23 to 1997-04-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study conducted under GLP.
Reference:
Composition 0
Composition 0
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: DR. K. THOMAE GMBH, BIBERACH, Germany
- Age at study initiation: Young adult animals of a comparable weight were used
- Weight at study initiation: males 180 - 183 g, females 169 - 171 g
- Fasting period before study: 16 hours prior to administration (but water ad libitum)
- Housing: Five animals per cage (type: stainless steel wire mesh cages, DK-III), no bedding
- Diet: KLIBA-LABORDIAET 343, KLINGENTALMUEHLE AG KAISERAUGST, SWITZERLAND, as libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): no data, however housing in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

IN-LIFE DATES: From: 1996-05-14 (day of first administration, before at least one week acclimatisation) To: 1996-05-23 (day of last administration)
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
bidest
Details on oral exposure:
The aqueous test substance formulation corresponds to the physiological medium.
Form of administration: emulsion

VEHICLE
- Concentration in vehicle: 20 g / 100 mL
- Amount of vehicle: 10 mL
- Justification for choice of vehicle: aqueous formulation corresponds to the physiological medium
- Purity: bidest water was used

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/ kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: A check for dead and moribund animals was made twice on workdays and once on the other days. Weighing of both groups on day 0, day 7; on day 13 (males) and day 14 (females).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, impaired general state, poor general state, dyspnoea, apathy, staggering, piloerection, salivation, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Males only: impaired or poor general state, dysponea, apathy, staggering, salivation. These symptoms are considered to be unspecific toxicity symptoms. The animals appeared normal one day after administration.
Body weight:
Mean body weight of males: 182 g on day 0, 248 g on day 7, 281 g on day 13
Mean body weight of females: 170 g on day 0, 205 g on day 7, 214 g on day 13
The expected body weight has been observed in the course of the study.
Gross pathology:
No abnormalities were noted at necropsy of animals sacrificed at the end of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw

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
Study period:
1997-10-09 to 1998-05-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study conducted under GLP.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: approx. 8 - 9 weeks
- Weight at study initiation: mean body weight males 269 g, mean body weight females 202 g
- Fasting period before study:
- Housing: Animals were housed singly in cages type DK III - Diet: KLIBA rat/mouse/hamster laboratory diet 10 mm pellets, Klingentalmühle AG, Kaiseraugst, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): no data, however the cages were housed in fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1997-10-09 To: 1997-10-23
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
Whole-body inhalation system IKA 02 (glass-steel construction), BASF Aktiengesellschaft.
Technical equipment: continuous infusion pump Perfusor VII (B. Braun), vaporizer with thermostat (glass, BASF), mixing vessel (glass, BASF)
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: the animals were kept singly in compartmentalized wire cages, and were exposed inside the chamber
- Source and rate of air: A Supply air flow (compressed air) of 3000 l/h was used for the test group. The exhaust air flow was 3200 L/h. An air changes of about 15 times per hour can be calculated by dividing the supply air flow by the volume of the inhalation system. The about 7% higher amount of exhaust air, which was adjusted by means of a separate exhaust air system, achieved a slightly negative pressure inside the exposure system. This ensured that no contamination of the laboratory occurred as result of possible leakages from the inhalation chamber. Additionally, the exposure system was located inside an exhaust cabin in the air-conditioned laboratory. The inhalation atmosphere was offered to the animals for inhalation for 4 hours after equilibration of the inhalation System (t99 about 20 min).
- Method of conditioning air: A vapour-air mixture was generated. For the test group the test substance was supplied to the heated vapouriser (about 49.5°C) by means of the continuous infusion pump. The vapours that developed were taken up by the supply air passed into the exposure System. Flow rate of the test substance to the atomizer was 25.0 mL/h.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: 24.2 °C, 12%, slightly negative pressure inside the exposure system

TEST ATMOSPHERE
- Brief description of analytical method used:
For the quantitative determination of the vapour concentration a gas chromatographical method was used.
Gas chromatographical analysis

Equipment: GC HP 5840 A (Hewlett Packard)
The following gaschromatographical conditions were used:
column: glass, 2 m x 3 mm
separation phase: 10% Ucon LB 550X
solid phase: Chromosorb W AW /HP 100/120 mesh
carrier gas: helium
carrier gas flow rate: 25.1 mL/min
hydrogen: 30 mL/min
air: 240 mL/min
temperature . 130°C/min
detector temp. (FID) : 2000C
injector temp.: 200°C
internal standard (i.st.): C12 KW
injection volume: 1µL
retention time (i.st.): 4.18 min
retention time sample: 2.90 min

Calibration:
Method set up:
During the set up of the analytical procedure a calibration curve was prepared in the solvent with the test substance to be investigated to show linearity in the suitable concentration range of the samples. The calibration curve of the substance in the solvent used had a linearity range from 20.2 to 60.6 mg/50 mL (method dated Oct. 06, 1997; for details see raw data).

Routine analysis during test period:
For routine analysis a one-point calibration of the analytical procedure was prepared for the analytical campaign based on the method mentioned above.

Sample preparation:
The samples obtained were taken up in 2-Propanole in a 50-mL calibrated flask. The flask was filled up to the calibration mark after an internal standard was added using a pipette.

Calculation of the concentration:
The concentrations were calculated in mg/L from the analytically determined mass values of the test substance and the sample volumes of the inhalation atmosphere.

- Samples taken from breathing zone: yes, sampling position immediately adjacent to the animals' noses
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Nominal: 7.48 mg/L
Analytical: 6.3 mg/L (maximum attainable vapour concentration)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The body weight of the animals was determined just prior to exposure, after 7 days and at the end of the observation period. A check for overt clinical signs of toxicity or mortality as well as a check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, irregular respiration, dragging respiration, attempts to escape, squatting posture, piloerection, body weight
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.3 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None
Clinical signs:
Attempts to escape, irregular and dragging respiration as well as squatting posture and piloerection. No clinical signs could be detected from post exposure day 5 onward.
Body weight:
Body weight development of the animals was not influenced.
Gross pathology:
No macroscopic pathologic findings were noted in animals examined at the end of the study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
6.3 mg/m³

Additional information

Acute oral toxicity study:

The study was performed to determine the acute toxicity following oral administration of Butandioldivinylether, applied as an emulsion in aqua bidest. in Wistar rats. The study procedure was based on the EEC guideline and modified according to the acute toxic class method. To a group of six fasted animals (3 males, 3 females) a single oral dose of the test material preparation in aqua bidest. at a dose level of 2000 mg/kg bw was given. Signs of toxicity noted in the male animals comprised impaired or poor general state, dyspnoea, apathy, staggering and salivation. These symptoms are considered to be unspecific toxicity symptoms. The animals appeared normal one day after application. The expected body weight gain has been observed in the course of the study. No mortality occurred. No abnormalities were noted at necropsy of animals sacrificed at the end of this study. Under the conditions of this study the median lethal concentration of Butandioldivinylether after oral application was found to be greater than 2000 mg/kg bw. for the male and female animals.

Acute inhalation toxicity:

For determination of the acute inhalation toxicity (single 4 -hour-exposure) of Butandioldivinylether as a vapour, a study in male and female Wistar rats was performed according to OECD-Guideline method 403, as well as EEC and EPA guidelines. The maximum attainable vapour concentration of 6.3 mg/L was tested. No mortality occurred at this concentration. The LC50 for male and female animals therefore is > 6.3 mg/L. Clinical examination revealed attempts to escape, irregular and dragging respiration as well as squatting posture and piloerection. No clinical signs could be detected from post exposure day 5 onward. Body weight development of the animals was not influenced. No macroscopic pathologic findings were noted in animals examined at the end of the study.


Justification for selection of acute toxicity – oral endpoint
Applicable to endpoint study, guideline-conform and conducted under GLP.

Justification for selection of acute toxicity – inhalation endpoint
Applicable to endpoint study, guideline-conform and conducted under GLP.

Justification for classification or non-classification

Acute oral toxicity

Dangerous Substance Directive (67/548/EEC)
The available study is considered reliable and suitable for classification purposes under Directive 67/548/EEC. As a result the substance is considered not to be classified for acute oral toxicity.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified for acute oral toxicity.

Acute inhalation toxicity

Dangerous Substance Directive (67/548/EEC)
The available study is considered reliable and suitable for classification purposes under Directive 67/548/EEC. As a result the substance is considered not to be classified for acute inhalation toxicity.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified for acute inhalation toxicity.