2-butyl-4,4,6-trimethyl-1,3-dioxane

Endpoint summary

Description of key information

A study was performed assessing the acute oral toxicity of the test substance in rats. The acute oral LD50 of the test substance was determined to be > 5.0 g/kg bodyweight. 
The test substance was examined for acute dermal toxicity in albino rabbits. The acute dermal LD50 of the test substance was found to be approximately 5.0 mL/kg body weight, equivalent to 4420 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

The study was conducted in 1977.

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Abstract only.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test substance was administered orally to 10 rats at 5 g/kg.

GLP compliance:

no

Test type:

other: No data

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

5 g/kg

No. of animals per sex per dose:

Ten, sex not specified.

Control animals:

no

Details on study design:

No data

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

not specified

Mortality:

There was no mortality during the study.

Clinical signs:

Piloerection, slight lethargy and ataxia.

Gross pathology:

Observations at necropsy included a large spleen in one animal and hernia (probably not related to the test substance) in one rat.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test substance was > 5.0 g/kg bodyweight.

Executive summary:

The test substance was administered orally to 10 rats at 5 g/kg. The acute oral LD50 of the test substance was > 5.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted in 1980.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards with acceptable restrictions.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Part of the trunk of the animals was freed from hair the day before the start of the experiment using electric clippers. The shaved area constituted approximately 10 % of the total body surface.
The test material was put into contact with the shaved skin. Dose levels were 0, 3.0, 5.0, and 9.0 mL/kg body weight. All dose levels were applied in the same volume of 9 mL/kg body weight by appropriate diluting with soya-bean oil.
Half of the animals received the material on the intact skin, the other half on the abraded skin The treated area was covered with a thin layer of cellulose sheet wrapped in polyethylene foil.
After an exposure period of 24 hours, the test substance was removed from the skin with water and the and the animals were wiped dry with towels. Subsequently they were caged individually in a room of constant temperature (approximately 18°C) and provided wiht the standard laboratory diet and tap water ad libitum.
After treatment the rabbits were observed for two weeks with regard to general appearance and behaviour, mortality, local skin reactions, growth and food and water intake.
At the end of the experimental period, examinations were carried out for possible changes in blood composition and several organs were investigated macroscopically. Sampes of the heart, liver, kidneys, spleen, stomach and of the treated and untreated skin were collected and kixed in 4 % neutral, phosphate-buffered formaldehyde solution for histological examination.

GLP compliance:

no

Remarks:

Study pre-dates GLP.

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: 2.40 to 2.97 kg

Type of coverage:

occlusive

Vehicle:

soya oil

Details on dermal exposure:

Part of the trunk of the animals was freed from hair the day before the start of the experiment using electric clippers. The shaved area constituted approximately 10 % of the total body surface.
The test material was put into contact with the shaved skin. All dose levels were applied in the same volume of 9 mL/kg body weight by appropriate diluting with soya-bean oil.
Half of the animals received the material on the intact skin, the other half on the abraded skin The treated area was covered with a thin layer of cellulose sheet wrapped in polyethylene foil.
After an exposure period of 24 hours, the test substance was removed from the skin with water and the and the animals were wiped dry with towels. Subsequently they were caged individually in a room of constant temperature (approximately 18°C) and provided wiht the standard laboratory diet and tap water ad libitum.

Duration of exposure:

24 hours

Doses:

0, 3.0, 5.0, and 9.0 mL/kg body weight.

No. of animals per sex per dose:

Two/sex/group

Control animals:

yes, concurrent vehicle

Details on study design:

After treatment the rabbits were observed for two weeks with regard to general appearance and behaviour, mortality, local skin reactions, growth and food and water intake.
At the end of the experimental period, examinations were carried out for possible changes in blood composition and several organs were investigated macroscopically. Sampes of the heart, liver, kidneys, spleen, stomach and of the treated and untreated skin were collected and kixed in 4 % neutral, phosphate-buffered formaldehyde solution for histological examination.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 mL/kg bw

Based on:

test mat.

Mortality:

At the end of the observation period, one rabbit of the low-dose group (no. 8534) was found dead. This rabbit had suffered from diarrhoea. Since no further mortality occurred, the dermal LD50 of the test substance appears to be about 5.0 mL /kg body weight.

Clinical signs:

During or at the end of the 24-hour exposure period, the following dermal effects and clinical symptoms were observed.
The control showed no abnormalities.
At 3.0 mL/kg: Slight to moderate erythema and slight edema.
At 5.0 mL/kg: Slight to moderate erythema and slight edema and apathy.
At 9.0 mL/kg: Moderate erythema and edema, apathy, salivation, dyspnoea, paresis and / or paralysis.
In the course of the 24-hour exposure period or the first days of the subsequent two-week observation period two rabbits of the mid-dose group (nos 8527 and 8541) and all rabbits of the high dose group were in poor condition and died or were killed when moribund.

In the course and at the end of the observation period, the surviving rabbits showed the following dermal effects:
At 3.0 mL/kg: No abnormalities.
At 5.0 mL/kg: Slight scaliness.
There were no distinct differences in reactions between rabbits treated on intact skin and those treated on the abraded skin.

Two animals that died during treatment (nos 8527 and 8541 of the mid-dose group) showed signs of diarrhoea.

Body weight:

Figures of growth and food and water intake showed some variation, but significant differences between test groups and controls did not occur.

Gross pathology:

At autopsy, the treated skin of the test animals was found to be only slightly affected by the compound under study. Five animals that died during the experiment (no. 8527 of the mid-dose group and all animals of the high dose group) showed slight haemorrhagic erosions in the stomach.
No other changes that could be ascribed to treatment were observed.
One animal of the low dose group (no 8524) and three animals of the mid-dose group (nos 8539, 8526 and 8527) showed slight redness and edema of the treated skin.

One animal that died during the experiment (no 8534 of the low-dose group) showed enlargement of the gall bladder and another animal that died (no 8527 of the mid-dose group) showed signs of haemorrhage in the urinary bladder).
At microscopic examinations, treatment-related histopathological changes were found in the treated skin of animals of the mid- and high-dose group.
One animal of the mid-dose group (no 8541) did not show any skin lesion, probably as a result of the very short survival time (the animal died within one day after application of the test substance), which allowed insufficient time for the lesion to develop.
The skin lesions were mainly characterised by necrosis, acanthosis, infiltration of polymorphonuclear granulocytes (leucocytes) in the dermis and slight fibroblastic repair activity.
Microscopy of the liver, kidneys, heart and spleen did not disclose any abnormalities that could be related to treatment. Gross and microscopic pathology did not provide any information to establish the cause of death of the animals that died during the experiment.
The observed microscopical changes were about equally distributed amongst control and test groups of occurred in a single animal only. Moreover, these lesions are common findings in the strain of rabbit used.

Other findings:

Haematological data of the surviving rabbits of the test groups were comparable with those of the controls.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

From the results of the acute dermal toxicity study, it is concluded that the dermal LD50 of the test substance is 5.0 mL/kg body weight.

Executive summary:

The test substance was examined for acute dermal toxicity in albino rabbits. The dermal LD50 of the test substance was found to be approximately 5.0 mL/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 420 mg/kg bw

Additional information

The test substance was assessed for acute oral toxicity of the test substance in 10 rats. Clinical signs, consisting of piloerection, slight lethargy and ataxia, were noted but there was no mortality during the study. The acute oral LD50 was determined to be > 5 g/kg bw.

The test substance was assessed for acute dermal toxicity of the test substance in albino rabbits. Erythema and edema were observed in all dose groups. Clinical signs, including apathy, salivation, dyspnoea, paresis and paralysis were observed. In the course of the 24-hour exposure period or the first days of the subsequent two-week observation period two rabbits of the mid-dose group and all rabbits of the high dose group were in poor condition and died or were killed when moribund. The acute dermal LD50 of the test substance was found to be approximately 5.0 mL/kg body weight.

Justification for selection of acute toxicity – oral endpoint
The study was conducted on the target substance in vivo, in an appropriate test species.

Justification for selection of acute toxicity – dermal endpoint
The study was conducted on the target substance in vivo, in an appropriate test species.

Justification for classification or non-classification

Acute toxicity is defined as the adverse effects occurring following a single administration of a substance, or multiple doses given within 24 hours by the oral or dermal routes, or an inhalation exposure of 4 hours.

Substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the Globally Harmonized Classification System and Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. Acute toxicity values are expressed as approximate LD50 or LC50 (inhalation) values.

A test substance is classified according to one of these four toxicity categories when the acute LD50 value is ≤ 2000 mg/kg for exposure via the oral or dermal route.

 

The acute oral LD50 of the test substance was 5000 mg/kg and is therefore not classified for acute oral toxicity.

The acute dermal LD50 of the test substance was 4420 mg/kg and is therefore not classified for acute dermal toxicity.