Reaction mass of 3,5,6,6-tetramethyl-4-methyleneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 September 1980 to 22 September 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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:

Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one

EC Number:

946-245-5

Molecular formula:

C12H22O

IUPAC Name:

Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one

Test material form:

liquid

Details on test material:

According to ECHA communication with reference to Annotation number: SUB-C-2114629169-42-01/F, the substance ID for Koavone has been changed with EC# from 939-627-8 to 946-245-5, and the IUPAC name from Reaction mass of (3R,5R)-3,5,6,6-tetramethyl-4-methylideneheptan-2-one and (3R,5S)-3,5,6,6-tetramethyl-4-methylideneheptan-2-one and (E)-3,4,5,6,6-pentamethylhept-3-en-2-one to Reaction mass of (E)-3,4,5,6,6-pentamethylhept-3-en-2-one and 3,5,6,6-tetramethyl-4-methyleneheptan-2-one.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Inc
- Age at study initiation: Approximately 6 weeks
- Weight at study initiation: The male rats was 155 to 200 g and for the female rats was 123 to 150 g
- Fasting period before study: Yes, approximately 19-20 hours overnight prior to dosage
- Housing: The rats were housed in groups (4-5 of like sex) in stainless steel wire mesh cages suspended above the droppings
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 9 days


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

IN-LIFE DATES: 5 September 1980 to 19 September 1980

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: alcohol SD39C

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 0.7 mL/ 100 g bw

Doses:

0.59, 1.00, 1.69, 2.88, and 5.0 g/kg of bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Closely observations for gross signs of systemic toxicity and mortality: At approximately 1-2, 3-4, 4-6 and 21-23 hours after treatment during the day of dosing, and twice daily thereafter for a total of 14 days.
- Necropsy of survivors performed: yes
- The protocol specified observations at 1, 3, 5 and 24 hours on the day of treatment.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

6.1 other: g/kg bw

Based on:

test mat.

95% CL:

> 3.51 - < 10.6

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2.35 other: g/kg bw

Based on:

test mat.

95% CL:

>= 1.31 - <= 4.21

Mortality:

The following deaths occurred within the first six days after the animals were treated with all but one occurring within the first three days:
0.59 g/kg bw: 2 females
1.00 g/kg bw: 3 females,
1.69 g/kg bw: 1 male and 4 females
2.88 g/kg bw: 2 males and 5 females
5.00 g/kg bw: 4 males and 7 females

Clinical signs:

other: Clinical changes included central nervous system depression (accompanied by changes such as loss of righting reflex, uncoordinated movement, partially closed eyelids, altered breathing and salivation) in all animals and bloating in males. At dosage of 0.5

Gross pathology:

Most of the animals that died during the course of the study exhibited staining about the mouth and nose externally. Internally, gas in the intestines and morphologic changes in the kidneys and liver were frequently present. Gross necropsies performed at the termination of the study were uneventful except for the presence of gas in the intestines and stomach of a few rats. No other gross pathology was seen.

Any other information on results incl. tables

Table 1. Mortality during the 14- day observation period.

Dosage	Sex	Hours		Days
g/kg		1	3	5	1	2	3	4	5	6	7-14
0.59	M	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10
0.59	F	0/10	0/10	1/10	1/10	2/10	2/10	2/10	2/10	2/10	2/10
1.00	M	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10	0/10
1.00	F	2/10	2/10	2/10	2/10	3/10	3/10	3/10	3/10	3/10	3/10
1.69	M	0/10	0/10	0/10	0/10	1/10	1/10	1/10	1/10	1/10	1/10
1.69	F	1/10	1/10	1/10	1/10	3/10	4/10	4/10	4/10	4/10	4/10
2.88	M	0/10	0/10	0/10	0/10	0/10	2/10	2/10	2/10	2/10	2/10
2.88	F	0/10	0/10	0/10	0/10	4/10	4/10	4/10	4/10	5/10	5/10
5.00*	M	0/10	0/10	0/10	0/10	2/10	3/10	4/10	4/10	4/10	4/10
5.00	F	0/10	0/10	0/10	1/10	3/10	7/10	7/10	7/10	7/10	7/10

* Data on all 10 rats included

- Values are number of animals dead/number of animals tested, cumulative.

Applicant's summary and conclusion

Interpretation of results:

other: not harmful

Remarks:

in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

Not harmful. In an acute oral toxicity study which was performed according to a method similar to OECD TG 401, the acute oral LD50 was found to be 6.10 g/kg bw for males with a 95% confidence limit of 3.51 - 10.6 g/kg, and 2.35 g/kg bw for females with a 95% confidence limit of 1.31 - 4.21 g/kg.

Executive summary:

The acute oral toxicity of the substance was evaluated in male and female Sprague-Dawley derived albino rats (10 animals per sex per dose), using a method similar to OECD TG 401. The animals were treated with the following dosages: 0.59, 1.00, 1.69, 2.88, and 5.0 g/kg bw by gavage. Gross signs of systemic toxicity, mortality, bodyweight was determined. Gross necropsy was performed after the 14- day observation period.

Deaths occurred within six days after treatment. Central nervous system depression was present in all groups after treatment. All animals which survived the observation period gained weight. Necropsies of animals which died revealed staining around the mouth, gas in the intestinal tract and changes in the kidneys and livers in most animals while necropsies of animals at the end of the observation period were generally uneventful. The acute oral LD50 was found to be 6.10 g/kg bw for male Sprague-Dawley derived albino rats with a 95% confidence limit of 3.51 - 10.6 g/kg. The LD50 for female Sprague-Dawley derived albino rats was found to be 2.35 g/kg bw with a 95% confidence limit of 1.31 - 4.21 g/kg.

Based on these results, the test substance is not harmful in accordance with EU CLP (EC no 1272/2008 and its amendments).