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Administrative data

Description of key information

Studies on acute toxicity of BVE are available:
The oral LD50 in male Wistar rats was 10300 mg/kg bw.
The LC50 (4h) in rats is >33.3 mg/L.
The dermal  LD50 in rabbits is 3300 mg/kg bw.

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: Comparable to guideline study with acceptable restrictions. Restriction: purity of TS not reported; non-fasted animals; no data about vehicle; no data about clinical signs, necropsy or body weight.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
Male Carworth-Wistar rats were used, 90 to 120 g in weight. Animals were kept on complete diet.
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
Rats not fasted before dosing; application volume 1-10 mL
Doses:
Dose levels were arranged in a logarithmic series differing by a factor of 2 (no further details).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Post exposure observation period 14 days
Statistics:
LD50-values were estimated by the method of Thompson using the tables of Weil, based on mortalities.
Sex:
male
Dose descriptor:
LD50
Effect level:
10 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: limits of +-1.96 standard deviations (calculated according to Thompson): 8400-12630 mg/kg bw
Mortality:
no further details
Clinical signs:
other: no data
Gross pathology:
no data
Other findings:
no data
Conclusions:
The LD50 in male Wistar rats was 10300 mg/kg bw; the post exposure observation period was 14 days. The Limit dose according to OECD TG401 is 5000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 300 mg/kg bw
Quality of whole database:
Comparable to guideline study with acceptable restrictions.
Restriction: purity of TS not reported; non-fasted animals; no data about vehicle; no data about clinical signs, necropsy or body weight

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: Comparable to the Limit test described in OECD TG403. Restriction: purity of TS not reported; concentration analytically not verified, no data on clinical signs or necropsy.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Toxic effects in rats after inhalation exposure for 4 h
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female Carworth-Wistar rats were used, 90 to 120 g in weight. Animals were kept on complete diet.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Metered atmospheres were generated by using pumps which delivered known amounts of TS to a stream of air. Concentrations are nominal, but not analytically verified; no further details
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
8000 or 16000 ppm corresponding to 33.3 or 66.6 mg/L
No. of animals per sex per dose:
6 rats
Details on study design:
Groups of 6 male or female rats were used. Mortalities noted during the 14-day observation period. Effect levels related to male and female rats combined.
Sex:
male/female
Dose descriptor:
LC0
Effect level:
8 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: (33.3 mg/L) 0 out of 6 rats died
Sex:
male/female
Dose descriptor:
LC100
Effect level:
16 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: (66.6 mg/L) 6 out of 6 rats died
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 33.3 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Recommended limit concentration according to OECD TG403 is 5 mg/L
Mortality:
no further details
Clinical signs:
other: no data
Body weight:
no data
Gross pathology:
no data
Conclusions:
No mortality was noted (0/6 animals died) in male and female Wistar rats following exposure to 8000 ppm (=33.3 mg/L) for 4 hours and a post exposure observation period of 14 days. However, a dose level of 16000 ppm (66.6 mg/L) for 4 h killed all 6 rats.
The LC50 (4) in rats is >33.3 mg/L (Limit dose according to OECD TG403 ist 5 mg/L).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
33.3
Quality of whole database:
Comparable to the Limit test described in OECD TG403. Restriction: purity of TS not reported; concentration analytically not verified, no data on clinical signs or necropsy.

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: Comparable to guideline study with acceptable restrictions. Restriction: purity of test substance not stated; no data on clinical signs; no necropsy; only males.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
Male albino New Zealand rabbits weighing 2.5 to 3.5 kg were used.
No further details.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Groups of 4 animals were used. Dosages were placed on the shaved rabbit skin under occlusive dressing (contact ca. 1/10 of body surface).
Duration of exposure:
24 h
Doses:
no details given
No. of animals per sex per dose:
4
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- no data about clinical signs & body weight
Statistics:
LD50-values were estimated by the method of Thompson using the tables of Weil, based on mortalities noted during the 14-day observation period.
Sex:
male
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: original value 4.24 mL/kg bw and limits of +-1.96 standard deviations (calculated according to Thompson): 3.02-5.95 mL/kg bw (2350-4630 mg/kg bw)
Mortality:
No further data available.
Clinical signs:
other: no data
Gross pathology:
no data
Conclusions:
In male New Zealand White rabbits the acute dermal toxicity was determined after an exposure period of 24 h (occlusive) and a post exposure period of 14 days. The LD50 is 4.24 mL/kg bw, i.e. 3300 mg/kg bw. The limit dose recommended in OECD TG402 is 2000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 300 mg/kg bw
Quality of whole database:
Comparable to guideline study with acceptable restrictions.
Restriction: purity of test substance not stated; no data on clinical signs; no necropsy; only males.

Additional information

Oral

The LD50 of BVE in male Wistar rats was 10300 mg/kg bw; the post exposure observation period was 14 days (Smyth et al., 1954). The limit dose according to OECD TG401 is 5000 mg/kg bw.

Inhalation

No mortality was noted (0/6 animals died) in male and female Wistar rats following exposure to 8000 ppm BVE (=33.3 mg/L) for 4 hours and a post exposure observation period of 14 days. However, a dose level of 16000 ppm (66.6 mg/L) for 4 h killed all 6 rats (Smyth et al., 1954). The LC50 (4) in rats is >33.3 mg/L (Limit dose according to OECD TG403 ist 5 mg/L).

In the inhalation hazard test (same publication) no mortality occurred in 6 male rats within 14 days after exposure for 5 min to saturated vapour.

Dermal

In male New Zealand White rabbits the acute dermal toxicity of BVE was determined after an exposure period of 24 h (occlusive) and a post exposure period of 14 days. The LD50 is 4.24 mL/kg bw, i.e. 3300 mg/kg bw (Smith et al., 1954). The limit dose recommended in OECD TG402 is 2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Comparable to guideline study with acceptable restrictions.

Justification for selection of acute toxicity – inhalation endpoint
Comparable to guideline study with acceptable restrictions.

Justification for selection of acute toxicity – dermal endpoint
Comparable to guideline study with acceptable restrictions.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC): the available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

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 not considered to be classified under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation No 605/2014.