5-methyl-2-(1-methylbutyl)-5-propyl-1,3-dioxane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study was non conducted under GLP as well as no citation of a guideline was presented. However, the study followed in main points the OECD TG 420 with the exception of the dose design and the use of male mice as test organisms.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

OECD TG 401 (adopted May 1981, deleted December 2002) and OECD TG 420 (originally adopted 1992) were not available at the conduct of the study, deviations to OECD TG 420: no fixed dose design, male mice as test organisms

Principles of method if other than guideline:

test doses determined for the calculation of a LD50 (no pre-experiment reported), administration of the test item by stomach tube , male mice as test organisms, 14 days of observation, determination of surviving animals, dead animals, animals with symptoms (general activity, tonic convulsions, delirium, lateral position, piloerection (i.e. occurrence of goose bumps))

GLP compliance:

no

Remarks:

GLP in the EU since 1981

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Troenan

IUPAC Name:

Troenan

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Troenan

Test animals

Species:

mouse

Strain:

CF-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann
- Age at study initiation: no data
- Weight at study initiation: average of 23 g
- Fasting period before study: no data
- Housing: no data
- Diet: deat not specified, presented in pressed form
- Water: water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22 °C
- Humidity (%): aapox. 50 %
- Air changes (per hr): not reported
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: dates not specified, during November 1980

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: dissolved in olive oil, but concentration of olice oil not specified
- Amount of vehicle (if gavage): 20 cm3/kg
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): not reported
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED:20 cm3/kg

DOSAGE PREPARATION: test substance dissolved in solvent

CLASS METHOD: not applicable
- Rationale for the selection of the starting dose: not reported

Doses:

501, 1000. 1990, 5010 and 6310 mg/kg, corresponding to 25.05, 50.00, 99.50, 250.00 and 316.00 g/L

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 3 hours, 28 hours, 7 days, 14 days after application
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

data from the treatments with 1000, 1990 and 5000 mg/kg used for statistics
test for log-normal distribution of data: chi2-test
determination of LD50, LD84 and LD16
determination of slope function S
calculation of confidence limits f using the formula f (LD50) = S ^ (2.77/sqroot N)
upper confidence limit: LD50 * f (LD50)
lower confidence limit: LD50 / f(LD50)

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

2 100 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 340 - <= 3 290

Mortality:

see Table 1

Clinical signs:

see Table 2

Body weight:

see Table 3

Gross pathology:

see Table 4

Other findings:

- Organ weights: not applicable
- Histopathology: not applicable
- Potential target organs: not applicable
- Other observations: not applicable

Any other information on results incl. tables

Table 1 Mortality and symptoms of toxicity

Dosis (mg/kg)	Conc. (g/L)	No. test organisms introduced	No. test organisms with symptoms	No. test organisms dead	% test organisms dead
501	25.05	10	10	0	0
1000	50.00	10	10	2	20
1990	99.50	10	10	5	50
5010	250.00	10	10	8	80
6310	316.00	10	10	10	100

Table 2 Symptoms of toxicity after 3 hours of exposure

Observed symptom	Rating (-4 as maximum decrease, 0 as normal, +4 as maximum increase)
General reactivity	-2
Tonic convulsions	+2
Delirium	+2
Lateral position	+1
Piloerection	+2

Table 3 Body weight

Dosis	Mean body weight (g)
(mg/kg)	before application	48 hours after application	7 days after application	14 days after application
501	22.10	23.31	24.79	26.87
1000	23.64	26.18	28.43	31.10
1990	22.90	25.68	28.90	30.43
2510	21.76	23.76	25.53	28.96
5010	26.07	27.24	29.75	32.75
6310	20.31	22.67	26.00	/

Table 4 Histopathology

Dosis (mg/kg)	Number of test organisms examined	Finding
501	3	no specific findings
1000	2	biting wounds at the lateral body areas
1990	5	no specific findings
2510	7	liver reduced in size, stoamch content bloddy in all examined test organisms
5010	9	no specific findings
6310	10	no specific findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a valid and reliable study, the oral acute toxicity of the test substance Troenan on male mice was determined. The LD50 was 2100 mg/kg body weight. Therefore, the test substance Troenan was considered to be slightly toxic.

Executive summary:

In a valid and reliable study, the oral acute toxicity of the test substance Troenan on male mice was determined. The LD50 was 2100 mg/kg body weight. The following symptoms of toxicity were observed: piloerection, tonic convulsions, lateral position, delirium and reduction of general health. The test item Troenan was considered to be slightly toxic.