1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 2nd March 1988 and 23rd March 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA FIFRA 81-3

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

EC Number:

402-950-5

EC Name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

Cas Number:

87826-41-3

Molecular formula:

C22 H26 O6

IUPAC Name:

(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-methylphenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Details on test material:

Substance: Geniset MD
Subsatnce identity: White solid powder
Batch number: 4140626
Date recieved: 18th Februray 1988
storage conditions: Stored in the dark at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Limited, Manston Road, Margate, Kent, England
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: ca 200 g
- Fasting period before study: not stated
- Housing: The cages were made of polypropylene (size 38cm x 56 cm x 18cm)
- Diet: free acess to food (Labsure LAD 1)
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20 and 22 deg C
- Humidity (%): mean of 41%

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Dust generator:
The test substance was placed into a concentric groove milled into the turntable and was continually added to the groove by hand, because the substance was not sufifciently free flowing to fill the groove by gravity feed from the hopper. As the turntable rotated, the dust passed under the air ejector and was aspirated into the chamber air supply.

Aerosol conditioning:
The test atmosphere produced by the generator was passed through a horizontal glass elutriation column to remove large non-respirable particles by sedimentation.

Exposure chambers:
The snout only exposure chambers were of cylindrical form (35.5 cm i.d., 38.5 cm in height) and made of perspex. The chambers were fitted with a hemispherical perspex top giving an enclosed volume of approximately 50 litres. The rats were held during exposure in perspex restraining tubes (22 cm x 6 cm i.d.) which were attached at evenly spaced ports around the cylindrical section of the chamber, and were designed to allow only the animals snouts to project into the chamber. Each rat was restrained in a forward position by an adjustable plastic stopper, which also provided a seal for the tube.

The conditioned test atmosphere entered the chamber through a port in the top section and passed out through small holes in the lower edge of the square section.

The exposure chamber and dust generator were positioned in a large cabinet equipped with an extract fan exhausting to the external atmosphere through a collection filter.

Exposure Procedure:
A supply of clean dried air was connected to the generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute. The turntable control was set to a speed of 0.7 revs per minute. The speed was selected in preliminary experiments and was the maximum practical.

The rats were placed into restraining tubes and the tubes were connected to the exposure chamber. The turntable motor was switched on and the exposure was timed for 4 hours following a 5 minute equilibration period. Following the required exposure period, the turntable was stopped and the exposure chamber was allowed to clear before the rats were removed for examination.

Chamber atmosphere analysis:
Five samples were taken from the chamber during the exposure and analysed gravimetrically to determine the achieved concentration of the test material in the chamber atmosphere.

Particle size distribution: 60% of the dust collected was 5.5 µm or less in aerodynamic diameter and therefore of respirable size.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The analysed mean concentration of test material was 0.67 mg/l, the highest attainable concentration.

The nominal concentration of test materila in the chamber atmosphere was 12.6 mg/l.

No. of animals per sex per dose:

5 males and 5 females per dose level

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days - The rats were observed continuously during exposure for clinical signs indicative of toxicity and at least twice daily throughout the 14 day observation period.
- Frequency of observations and weighing: Each rat was weighed daily until the end of the observation period.
- Necropsy of survivors performed: yes - the rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissues and weighed in order to calculate the lung weight to bodyweight ratio.
- Other examinations performed: Food and water consumption.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.67 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Analysed mean concentration

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 12.6 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: During exposure: All rats were normal in appearance and behaviour apart from soiling of the body fur due to restraint. During the observation period: When the rats were removed from the exposure chamber all rats were soiled with urine and faeces due to

Body weight:

Small losses in bodyweight or a reduced rate of bodyweight gain obsevred in a proportion of control rats and also in a proportion of the rats exposed to the test material. This was considered due to the restraint. There were no affects on bodyweight associated with exposure to the test substance.

Gross pathology:

There were no macroscopic abnormalities in any of the rats.

Other findings:

Food and water consumption: Food and water consumption were slightly reduced for 1 day following exposure in Groups 1 (control) and 2 (Test). This was considered to be due to restraint. There was no effect of exposure to the test material.

Lung weight to bodyweight ratio: The ratio was considered to be within normal limits for all rats.

Any other information on results incl. tables

Estimation of the LC₅₀ (4 -hour):

There were no deaths following a 4 hour exposure to the test material at an analysed concentartion of 0.67 mg/l of air. This was the highest attainable concentration with the equipment used. The LC₅₀ (4 hour) for the test material is therefore in excess of 0.67 mg/L of air.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute inhalation LC50 (4 hour) of the test material to rats, using a snout only exposure system was in excess of 0.67 mg/l, the maximum attainable concentration.

Executive summary:

The study was conducted in compliance to the OECD Guideline 403 and EPA FIFRA 81 -3.

5 male and 5 female rats were used in one test group and in one control group. The route of administration was by snout-only inhalation of a test atmosphere containing dust generated from the test substance. The duration of exposure (snout only) was 4 hours and the subsequent observation period was 14 days.

The analysed mean concentration of test substance was 0.67 mg/l, which was the highest obtainable concentration.. Approximately 60% by weight of particles were less than 5.5 µm in aerodynamic diameter and therefore of respirable size.

There were no deaths, no treatment related effects (clinical signs), no effect on bodyweight, no effect on food and water consumption. The lung weight to bodyweight ratio for all rats was within normal limits. There were no macroscopic abnormalities in any of the rats.

The acute inhalation LC50 (4 hour) of the test material to rats, using a snout only exposure system was in excess of 0.67 mg/l, the maximum attainable concentration.

The nominal concentration was 12.6 mg/l.