Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
other: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From March 29 to May 22, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Source study has reliability 1. Details on the read across are attached in section 13.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Acclimation period: 5 days
- Source: Winkelmann, Borchen
- Age at study initiation: 8 weeks (M), 10 weeks (F)
- Average weight at study initiation: 179 g (M), 178 g (F)
- Housing: Makrolon Cages Type III, with antidust pellet Holgranulat (FIRMASSNIFF, Soest/Westfallen)
- Diet: Altromin®1324 Pellets (Altromin GmbH, Lage)
- Water: drinkable water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 50 ± 10%
- Photoperiod: 12h / 12h (light from 6 to 18)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mg/kg
Doses:
200, 350, 500, 1000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice a day
- Frequency of weighing: before administration, after 1 week to the administration, at the end of observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
Spearmann & Kärber Method

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 395 mg/kg bw
Based on:
test mat.
95% CL:
ca. 164 - ca. 626
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 275 mg/kg bw
Based on:
test mat.
95% CL:
ca. 188 - ca. 738
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 177.8 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 124 mg/kg bw
Based on:
act. ingr.
Mortality:
Male:
200 mg/kg (no animal died, 0 % mortality)
350 mg/kg (3 animals died after 1h from administration, 60 % mortality)
500 mg/kg (3 animals died from 2 to 4 h after administration, 60 % mortality)
1000 mg/kg (5 animals died after 1h from administration, 100 % mortality)

Female:
200 mg/kg (1 animal died after 2h from administration, 20 % mortality)
350 mg/kg (4 animals died from 1 to 4 h after administration, 80 % mortality)
500 mg/kg (5 animals died after 2h from administration, 100 % mortality)
1000 mg/kg (5 animals died after 1h from administration, 100 % mortality)
Clinical signs:
Sedation, abdominal position, cramps, gasping
Body weight:
Growth not influenced
Gross pathology:
Negligible hystological examination
Other findings:
At pathological-anatomical examination of animals dead upon doses of 200 to 1000 mg/kg, the gastric mucosa had passed, the fundus of the stomach and the intestines reddened; in a male and female of dose 350 and in several animals at doses of 500 and 1000 mg/kg, the lung was red.

Any other information on results incl. tables

Males

dose 200 350 500 1000
vol. administered 10 10 10 10
no. died animals 0 3 3 5
no. of animals with symptoms 0 5 5 5
no. used animals 5 5 5 5
beginning of symptoms 30' 15' 15'
end of symptoms 1d 1d 1h
death 1h from 2h to 4h 1h

no. of animals/intensity

(1 = low, 2 = medium, 3 = high)

general condition 3/1
sedation 5/3 5/3 5/3
abdominal position 4/1 4/1 5/1
cramps 1/1
gasping 4/1 5/1

Females

dose 200 350 500 1000
vol. administered 10 10 10 10
no. died animals 1 4 5 5
no. of animals with symptoms 2 5 5 5
no. used animals 5 5 5 5
beginning of symptoms 30' 30' 15' 15'
end of symptoms 2h 4h 2h 1h
death 2h from 1h to 4h 2h 1h

no. of animals/intensity

(1 = low, 2 = medium, 3 = high)

sedation 2/1 4/3 5/3 5/3
abdominal position 2/1 4/1 5/1 5/1
gasping 2/2 4/1 5/1 5/1

Applicant's summary and conclusion

Interpretation of results:
other: cat. 3, according to the CLP Regulation (EC 1272/2008)
Conclusions:
LD50 (male) = 395 mg/kg.
LD50 (female) = 275 mg/kg.
Executive summary:

Method

The substance was tested according to the EU method B.1. Five rats per sex per dose have been used at concentrations of 200, 350, 500, 1000 mg/kg. Effects and mortality were recorded.

Results

Clinical signs and mortality were observed from 15 minute to 1 day after the administration. LD50 of the substance for male rats is 395 mg/kg (177.8 mg/kg a.i.), and for female rats is 275 mg/kg (124 mg/kg a.i.).

Clinical signs in terms of sedation, abdominal position, cramps and gasping were noted. Males dosed at dose of 200 mg/kg (90 mg/kg a.i.) were without symptoms.