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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Oct - 12 Dec 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (non GLP, test substance not characterized in detail).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
non GLP, test substance not characterized in detail
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: yellowbrown, oily liquid
- Purity test date: not specified

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Fasting period before study: 16 h
- Housing: 5 animals per cage in Makrolon 3 cages
- Diet: Altromin-Haltungsdiät 1324, Fa. Altromin, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 45 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% (g/V) for 2000 mg/kg bw and 2% (g/V) for 200 mg/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
200, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for clinical signs and mortality regularly on day of application and 2 x daily thereafter, weighing was carried out one day before application, on day of application and 2, 7 and 14 days following application
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no substance related death at 200 mg/kg bw, but all animals died at the highest dose of 2000 mg/kg bw
Mortality:
Neither female nor male animals died in the 200 mg/kg bw test group. Only one male animal had to be killed after 52 hours, but this was due to mistake during gavage. In the 2000 mg/kg bw test group 4 male animals and all female animals died within the first 30 hours after dosing. The additional male animal died 48 hours after application. Thus, mortality was 100% at 2000 mg/kg bw.
Clinical signs:
Female animals dosed with 200 mg/kg bw did not show any clinical signs. The one male animal that died due to gavage error showed decreased activity, brownish colored nose, vocalization, diarrhoea, severe reduction of body weight and chromodacryorrhoea but this was due to gavage error. The remaining males showed no clinical signs.
All 5 female animals dosed with 2000 mg/kg bw showed slight piloerection 2.5 h after dosing. 4 h post dosing 3 females showed slight piloerection and diarrhoea. 6 to 24 h post dosing all female animals showed strong piloerection, decreased activity, squatting posture and incomplete lid closure. 3 female animals additionally showed diarrhoea. 24 to 28 h post dosing strongly decreased activity, severe diarhoea, decreased temperature, ataxia, belly-side location and difficulty breathing were observed.
Vocalization and slight salivation was observed for 1 male animal 15 minutes after dosing with 2000 mg/kg bw. 2 additional male animals showed slight piloerection and slight to strong salivation. 1.5 to 2.5 h post dosing 1 male animal showed decreased activity, vocalization and slight piloerection. 2 additional animals also showed slight piloerection. 4 hours post dosing, 1 male animals had a brownish clored nose, decreased activiy, and piloerection, the other 4 male animals showed slight to strongly decreased activity and also piloerection. 6 to 24 hours post dosing 1 male animal showed strongly reduced activity, complete lid closure, strong piloerection and squatting posture. Another animal showed severely decreased activity and strong piloerection and a third animal equally showed severely decreased activity but only slight piloerection. Severely decreased activity, piloerection, squatting posture which changed to belly location, difficulty breathing, and slightly to strongly discoloured brown nose and/or snout were observed 24 h post dosing (3 male), 30 h post dosing (2 male) and up to 48 h post dosing (1 male).
Body weight:
All animals in the 200 mg/kg bw group showed normal body weigh gains at the end of the study period. In the 2000 mg/kg bw group body weigth was not assessed since all animals died within 2 days.
Gross pathology:
For the animals dosed with 200 mg/kg bw no abnormal findings at gross necropsy were detected. 2 male animals dosed with 2000 mg/kg bw showed a severe gaseous distention of the small intestine and all 5 female animals showed a slight to severe gaseous distention of the small intestine and the stomach. 1 female animal had a red discolored glandular stomach and the duodenum filled with liquid. 2 male animals and all 5 female animals showed a severe hydrothorax, 2 male animals had redness of the fundus area and moderate ascites. 1 male animal had a filled small intestine, slight ascites and a slight hypothorax.

Any other information on results incl. tables

Table 1. Table for acute oral toxicity. 

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

200

1/1/5

Day 1

---

20

2000

5/5/5

Day 1

24-48 h

100

Females

200

0/0/5

Day 1

---

0

2000

5/5/5

Day 1

24-28 h

100

LD50 = 174 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used         

Applicant's summary and conclusion