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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:
From Aug. 6, 1981 to Sep. 28, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
-No individual data; justification for choice of vehicle was not provided
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Liquid

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Raised on the premises (CIBA-GEIGY Limited, Experimental Toxicology Sisseln GU 2.1)
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 200-214 g for males and 176-181 g for females
- Fasting period before study: Animals fasted overnight before orally treated
- Housing: Housed in groups of 5 in Macrolon cages (type 3)
- Diet: NAFAG No. 890, NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: A minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: polyethylene glycol 400
Details on oral exposure:
VEHICLE:
Polyethyleneglycol 400 (PEG 400), Fluka AG, Buchs, SG
- Amount of vehicle (if gavage): 10 and 20 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

DOSAGE PREPARATION:
The test substance was diluted to achieve a concentration suitable for the dose levels selected for this test.
Doses:
1000, 2500 and 5000 mg/kg body weight.
No. of animals per sex per dose:
10 animals per sex per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately prior to dosing and at 7 and 14 days. Physical condition and rate of deaths were monitored throughout the whole observation period.
- Necropsy of survivors performed: Yes, all animals were submitted to a necropsy, whenever they died, survivors at the end of the observation period.

Toxicity rating was evaluated according to company standards (see Table 1).
Statistics:
The LD50, including the 95% confidence limits were calculated by the logit model.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 230 mg/kg bw
95% CL:
2 615 - 4 247
Mortality:
For one sex (not further specified), no deaths were reported in the 1,000 and 2,500 mg/kg groups, nine deaths were reported in the 5,000 mg/kg group: 1 animal died 3 hours after treatment; 4 animals died 24 hours after treatment; 3 animals died 2 days after treatment; 1 animal died 3 days after treatment.

In the other sex (not specified), 2 deaths were reported in the 2,500 mg/kg group and 10 deaths were reported in 5,000 mg/kg group (sex not specified). In the 2,500 mg/kg group, 2 animals died 2 days after treatment. In the 5,000 mg/kg group, 1 animal died 3 hours after treatment; 2 animals died 5 hours after treatment; 6 animals died 24 hours after treatment; 1 animal died 2 days after treatment.
Clinical signs:
The surviving animals recovered within 5-9 days.
In the 1,000 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 8; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 7; slight diarrhoea was observed at 24 hours and at Day 2; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 4.
In the 2,500 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 3; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 8; slight exophthalmos was observed at Day 2; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 7; slight diarrhoea was observed at 24 hours and at Day 2; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 5.
In the 5,000 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 3; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 5; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 6; slight diarrhoea was observed at 24 hours; ventral body position was observed at 3, 5, and 24 hours; slight lateral body position was observed at 2, 3, 5, and 24 hours; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 4; moderate tremor was observed at 2 hours and slight tremor was observed at 3, 5, and 24 hours; slight convulsions were observed at 24 hours.
These clinical signs are common effects in this type of study.
Body weight:
See Table 2 for body weight changes.
Gross pathology:
No compound related gross organ changes were observed.
Other findings:
Not applicable.

Any other information on results incl. tables

Table 2. Body weights in grams and standard deviation

Dose (mg/kg)

Males

Females

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

1,000

200 ± 9.1

246 ± 9.9

289 ± 7.6

180 ± 5.3

197 ± 6.7

216 ± 6.6

2,500

214 ± 6.7

252 ± 7.3

290 ± 6.9

176 ± 3.8

200 ± 5.2

219 ± 6.0

5,000

207 ± 6.7

-

-

181 ± 2.9

-

-

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is 3230 (2615-4247) mg/kg bw.