[1α(E),2β]-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

Acute Toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

1-(2,6,6-trimethyl-3-cyclohexen-1-yl)-2-buten-1-one

EC Number:

260-709-8

EC Name:

1-(2,6,6-trimethyl-3-cyclohexen-1-yl)-2-buten-1-one

Cas Number:

57378-68-4

IUPAC Name:

1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

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 or test system 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 levels

Effect levels 1

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)

Effect levels 2

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)

Effect levels 3

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:

other: 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

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