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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:
12 Feb - 5 Mar 1980
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:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1981)
GLP compliance:
yes
Remarks:
A statement of the Quality Assurance Unit was added.
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.1%
Physical appearance: solid

Test animals

Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males: 176-204 g; females: 180-197 g
- Fasting period before study: Fasted overnight
- Housing: 5 animals per Makrolon cage (type 3)
- Diet (ad libitum): NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Photoperiod (hrs dark / hrs light): 10 h light day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG400
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg bw


DOSAGE PREPARATION:
Test substance was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Doses:
4000, 5000, 6000, 7000 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
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight (prior to treatment, day 7, day 14)
Statistics:
LD50 including 95% confidence limits are calculated by the logit model.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred.
Clinical signs:
4000 mg/kg bw: dyspnoea (slight, until day 6), exophthalmus (slight, until day 3), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
5000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 3), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
6000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 4), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4)
7000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slight, until day 6), exophthalmus (slight, until day 5), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 5)
Body weight:
see table 1
Gross pathology:
No substance related gross organ changes were seen.

Any other information on results incl. tables

Table 1: Mean body weight of male and female rats [g] at day 1, 7, and 14.

Mean body weight [g] ± sd

4000 mg/kg bw

5000 mg/kg bw

6000 mg/kg bw

7000 mg/kg bw

Day 1 male

204±10

176±11

201±19

186±18

Day 1 female

192±10

180±12

197±21

188±8

Day 7 male

245±9

234±10

248±11

230±9

Day 7 female

219±10

204±16

201±14

202±5

Day 14 male

291±21

284±10

288±9

284±10

Day 14 female

223±20

217±25

224±20

216±4

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 in the rat is greater than 7000 mg/kg body weight.
Executive summary:

In an acute oral toxicity study five male and five female Tif: RAIf (SPF) rats were treated with test substance in PEG at dose levels of 4000, 5000, 6000, and 7000 mg/kg by gavage. Within the observation period of 14 days dyspnoea, exophthalmus, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. No mortality occurred. No substance related gross organ changes were seen. Based on the results of this study, an LD50 of > 7000 mg/kg bodyweight was derived.