Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline, animal experimental study, limitations in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity).
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
colorless liquid
Code No. SG 082367 (17151)
FDRL Identification No. 78-0554

Test animals

Species:
mouse
Strain:
other: BLU: Ha (ICR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Inc., Altamont, NY
- Weight at study initiation: between 15 - 36 grams
- Fasting period before study: The animals were fasted overnight (approximately 18 hours) prior to dosing
- Housing: plastic cages with wood shavings as bedding, in groups of five
- Diet (e.g. ad libitum): Charles River pelleted RMH 3000 supplied ad libitum after dosing
- Water (e.g. ad libitum): supplied ad libitum after dosing
- Acclimation period: at least three days prior to test initiation

ENVIRONMENTAL CONDITIONS
- Temperature: 70 ± 3°F

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test material was administered as a corn oil solution at varying concentrations, at a constant volume of 20 ml/kg.
Doses:
Three preliminary searches were performed before the actual LD50 was set up. The design represented in the table of log dose schedule, as supplied by the client, was used as a tool for dosage selection.
Dose levels: 940, 1346, 1475, 1600, 1902, 2025, 2150, 2225, 2350, 2692 mg/kg
No. of animals per sex per dose:
5 male and 5 females
Control animals:
no
Details on study design:
Animals were observed for 14 days following administration of the test material. Toxic effects and mortality were recorded throughout the duration of the test period.
Statistics:
First the LD50 was calculated by the methos of Knudsen and Curtis; only three to four dose levels were used and the resulting 95% confidence intervals appeared to be smaller than felt the data warranted. Recalculation was done by Finney Probit analysis (December 7, 1979)

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
95% CL:
>= 1 085 - <= 1 806
Remarks on result:
other: based on the recalculation by Finney Probit analysis (December 7, 1979)
Sex:
female
Dose descriptor:
LD50
Effect level:
1 850 mg/kg bw
Remarks on result:
other: 95% CL cannot be calculate from this data; based on the recalculation by Finney Probit analysis (December 7, 1979)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 625 mg/kg bw
95% CL:
>= 1 332 - <= 1 990
Remarks on result:
other: based on the recalculation by Finney Probit analysis (December 7, 1979)
Mortality:
Male;
940 mg/kg bw: 2/5 animals
1346 mg/kg bw: 0/5 animals
1475 mg/kg bw: 2/5 animals
1600 mg/kg bw: 4/5 animals
1902 mg/kg bw: 4/5 animals
2025 mg/kg bw: 4/5 animals
2150 mg/kg bw: 4/5 animals
2225 mg/kg bw: 3/5 animals
2350 mg/kg bw: 4/5 animals
2692 mg/kg bw: 4/5 animals

Female;
940 mg/kg bw: 0/5 animals
1346 mg/kg bw: 0/5 animals
1475 mg/kg bw: 1/5 animals
1600 mg/kg bw :4/5 animals
1902 mg/kg bw: 5/5 animals
2025 mg/kg bw: 5/5 animals
2150 mg/kg bw: 4/5 animals
2225 mg/kg bw: 3/5 animals
2350 mg/kg bw: 5/5 animals
2692 mg/kg bw: 5/5 animals
Clinical signs:
Males;
All animals at all doses showed decrease of activity.
Ataxia at all dose levels, not with all animals. Salivation at dose 1600 with 3 animals. Urinary incontinence at all doses (except 1475 and 2692), not all animals. Tremors at all doses >1600 (except 2692), not all animals. Death at all doses >1346 (except 2692), not all animals.
Females;
All animals at all doses showed decrease of activity.
Ataxia at all dose levels, not with all animals. Salivation at dose 1600 with 3 animals. Urinary incontinence at all doses (except 2692), not all animals. Tremors at all doses >1475 (except 2692), not all animals. Death at all doses >1475 (except 2692), not all animals.
Body weight:
Male;
Dose: 940 mg/kg bw; initial 23.20 ± 1.66, 14 days 31.00 ± 2.00
Dose: 1475 mg/kg bw; initial 22.40 ± 1.69, 14 days 27.67 ± 1.45
Dose: 1600 mg/kg bw; initial 27.20 ± .97, 14 days 37.00
Dose: 1902 mg/kg bw; initial 27.00 ± 1.30, 14 days 35.00
Dose: 2025 mg/kg bw; initial 25.00 ± 1.45, 14 days 35.00
Dose: 2150 mg/kg bw; initial 25.80 ± .97, 14 days 28.00
Dose: 2225 mg/kg bw; initial 28.00 ± 1.95, 14 days 35.00
Dose: 2350 mg/kg bw; initial 25.40 ± .81, 14 days 30.00
Dose: 2692 mg/kg bw; initial 25.60 ± 1.63, 14 days 31.00

Female;
Dose: 940 mg/kg bw; initial 23.00 ± 1.14, 14 days 34.80 ± 1,53
Dose: 1475 mg/kg bw; initial 21.20 ± 0.58, 14 days 23.00 ± 1.22
Dose: 1600 mg/kg bw; initial 27.40 ± 1.03, 14 days 30.00
Dose: 1902 mg/kg bw; initial 25.20 ± .37
Dose: 2025 mg/kg bw; initial 25.40 ± .68
Dose: 2150 mg/kg bw; initial 23.60 ± .68, 14 days 30.00
Dose: 2225 mg/kg bw; initial 24.80 ± .92, 14 days 32.00 ± 2.00
Dose: 2350 mg/kg bw; initial 23.40 ± 1.36
Dose: 2692 mg/kg bw; initial 25.40 ± 1.50
Gross pathology:
Summary of Necropsy Findings (Combined Data Males and Females):
Dose 940 mg/kg: Intestines: vascularized.
Dose 1346 mg/kg: No deaths.
Dose 1475 mg/kg: Lungs: dark. Liver: pale. Spleen: pale, pale and granular; appears large. Kidneys: pale. G.I. Tract: filled with brown fluid. Intestines: white. Stomach: fluid filled.
Dose 1600 mg/kg : Lungs: pale. Liver: pale. Kidneys: pale. Spleen: dark. G.I. Tract: containing yellow like substance. Stomach: full.
Dose 1902 mg/kg: Lungs: dark. Liver: pale. Kidneys: pale and mottled. Spleen: dark.
Dose 2025 mg/kg: Lungs: dark. Liver: pale. Kidneys: pale and mottled. Spleen: pale.
Doses 2150 mg/kg: Lungs: pinkish gray. Liver: pale. Kidney: pale and mottled. Spleen: dark.
Other findings:
no data

Applicant's summary and conclusion