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Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
other information
Study period:
08 Feb - 24 Feb 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD No. 401, EEC Directive 92/69/EEC, Annex, Part B (B.1)
Deviations:
yes
Remarks:
i.v. ; This study was carried out with three dose levels (500, 750 and 1000 mg/kg bw, using five female albino rats for each dose level and five males for the two high dose levels (i.v.))
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Prouvital, code GBR 50009
- Physical state / appearance: dark-brown, viscous liquid (described by sponsor as black liquid)
- Analytical purity: 100%
- Lot/batch No.: 93/204
- Storage condition of test material: in the dark at room temperature

Test animals

Species:
rat
Strain:
other: Wistar outbred rats Crl: WI (WU) BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: 8 weeks old
- Housing: 5 animals/cage (stainless steel cages, 45x32x18 cm, fitted with wire screen floor and front)
- Diet (e.g. ad libitum): standard laboratory rat diet
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 42.5 - 72.5
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: demineralized water
Details on exposure:
The exact volume of the test dilution to be dosed was calculated for each animal individually and applied by syringe, equipped with a needle suitable for intravenous injection.
(viz. 2.5, 3.75 and 5 mL/kg body weight)
Doses:
500, 750 and 1000 mg/kg bw
(preliminary test: 2000, 1000, 750, 500, 250 mg/kg bw)
No. of animals per sex per dose:
5 (males without the low dose level group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (observations were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout an observation period of 14 days)
- Frequency of observations and weighing: immediately before dosing and on day 3, 7 and 14 of the study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathological changes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: intravenous; some animals were reanimated
Mortality:
Two males and one female showed dyspnoea and coma, immediately after dosing (750 mg/kg bw) and needed reanimation to survive.
Immediately after dosing (1000 mg/kg bw) two males showed dyspnoea and coma and needed reanimation. Within ten minutes after dosing , despite reanimation, one male died. At the same doses of 1000 mg/kg bw four females showed dyspnoea and coma, immediately after dosing and needed reanimation to survive.
Clinical signs:
500 mg/kg bw: At 4 hours after dosing, sluggishness was observed in all females, while a swollen nose was observed at 1 and 4 hours after dosing.
750 mg/kg bw: Immediately after dosing until 4 hours after dosing, sluggishness was observed in all males and females. A swollen nose was observed in males at 1 hour after dosing and in females at 1-4 hours after dosing. In addition, the males showed swollen legs at 1-4 hours after dosing and females piloerection at 1 hour after dosing or at 4 hours after dosing. Two males and one female showed dyspnoea and coma.

1000 mg/kg bw: Two males showed dyspnoea and coma immediately after dosing. Immediately after dosing until 4 hours after dosing, sluggishness, swollen legs and nose were observed in all males (except one). In addition, the males showed a blue discolouration at 1 hour after dosing. One male showed vocalization at 4 hours after dosing. In females, sluggishness (at 1 hour after dosing), swollen nose (at 1-4 hours after dosing) and piloerection (at 4 hour after dosing) were observed. One female showed endogenous blue discolouration. Four females showed dyspnoea and coma immediately after dosing (and needed reanimation to survive).

all doses: During the remainder of 14-day observation period, no clinical symptoms were observed.
Body weight:
Generally, all surviving animals gained weight during the 14-day observation period.
One male and one female both treated with the 750 mg/kg bw dose level showed a very minor dip in body weight.
Gross pathology:
Macroscopic examination of the animals did not reveal any treatment-related gross alterations at the end of the observation period. The one male that died also did not reveal treatment-related gross alterations.

Any other information on results incl. tables

Table 1: Summary of clinical symptoms and incidences

Observation

500 mg/kg bw

750 mg/kg bw

1000 mg/kg bw

Female

Male

Female

Male

Female

Sluggishness

5/5

5/5

5/5

5/5

5/5

Swollen nose

5/5

5/5

5/5

4/5

5/5

Swollen legs

 -

5/5

 -

4/5

 -

Piloerection

 -

 -

5/5

 

5/5

Blue discolouration

 -

 -

 -

4/5

1/5

Vocalization

 -

 -

 -

1/5

 -

Dyspnoea

 -

2/5

1/5

2/5

4/5

Coma

 -

2/5

1/5

2/5

4/5

Reanimation

 -

2/5

1/5

2/5

4/5

Death

 -

 -

 -

1/5

 -

Applicant's summary and conclusion