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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:
2 December 1982 - 21 December 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Reliability 2 is assigned because the study was used for read-across.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Age at study initiation: No data
- Weight at study initiation: 180-280 grams (after fasting)
- Fasting period before study: 18 hours
- Housing: Individually in stainless steel wire mesh cages
- Diet (e.g. ad libitum): Ad libitum (Wayne Lab Blox)
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Remarks:
0.25% concentration
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2, 0.32, 0.4, 0.5 and 0.64 g/ml

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
Doses:
1000, 1600, 2000, 2500, 3200 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: 1 hour, 4 and 24 hours and twice daily.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs (pharmacotoxic, CNS effects and mortality), body weights (after fasting and on the 14th day of the observation period).
Statistics:
LD50 was determined with the method of Litchfield and Wilcoxon.

Results and discussion

Preliminary study:
None of the rats died at 500 mg/kg bw, one rat died at 1600 mg/kg bw and all rats died at 5000 mg/kg bw. Clinical signs observed were body drop, ptosis, diarrhea, decreased activity, decreased body tone, poor grooming, abnormal stance, hypersensitivity, piloerection, chromodacryorrhea and prostration.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 609.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 399.6 - <= 1 850.4
Mortality:
- 1000 mg/kg bw: no mortality
- 1600 mg/kg bw: 5/10 animals died
- 2000 mg/kg bw: 9/10 animals died
- 2500 and 3200 mg/kg bw: 10/10 animals died
Clinical signs:
Semi-prostration, abnormal gait, body drop, exophthalmus, decreased activity, dyspnea, tremors, ataxia, ptosis, diarrhea, decreased body tone, hypersensitivity, hyperactivity and chromodacryorrhea.
Body weight:
No treatment related changes were recorded during the study period.
Gross pathology:
Distended stomachs with hemorrhages present on the mucosa, distended bladders, red foci on the thymus and discolored adrenals. In the surviving animals no visible lessions were observed via terminal necropsy.

Any other information on results incl. tables

An acute oral LD50 for females was not calculated as the data generated were not suitable to be analysed with the statistical method chosen.

Applicant's summary and conclusion

Interpretation of results:
other: Category 4
Remarks:
According to EU CLP 1272/2008 and its amendments.
Conclusions:
Under the conditons of this study, the acute oral LD50 in male and female rats was determined to be 1609.3 mg/kg bw for Etaphen. Based on these results, the substance needs to be classified as Acute Tox. Category 4 in accordance with the criteria outlined in Annex I of CLP (1272/2008/EC) and its amendments.
Executive summary:

In this study, 5 groups of 10 rats (5 males and 5 females) were administered Etaphen at dose levels of 1000, 1600, 2000, 2500 and 3200 mg/kg bw. Animals were observed for 14 days. None of the 10 test animals died at 1000 mg/kg, 5 out of 10 died at 1600 mg/kg, 9 out of 10 died at 2000 mg/kg, and all rats died at the 2500 and 3200 mg/kg levels. Observed clinical signs included body drop, prostration, exophthalmus, decreased activity, semi-prostration, abnormal gait, dyspnea, tremors, ataxia, ptosis, diarrhea, decreased body tone, hypersensitivity, hyperactivity and chromodacryorrhea. The acute oral LD50 for the substance in male and female rats was determined to be 1609.3 mg/kg bw with a 95% CI of 1399.6 to 1850.4 mg/kg bw and is considered harmful.