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

Endpoint summary

Description of key information

Acute oral LD50: > 12 g/kg bw
Acute dermal LD50: > 2100 mg/kg bw
Acute inhalation LD50: > 0.67 mg/l air (>670 mg/m3)

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:

key study

Study period:

Study conducted between Januray 1982 and April 1982.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

The rats were divided into four groups, each composed of 10 males and 10 females. Three dose levels of the analyte were administered (3, 6 or 12 g/kg), based on the maximum physical intake capacity of rats as determined by previous experimentation. As a control , one group was given 4 ml/100 g (weight) of 5% gum arabic, the same quantity as the group that received the maximum analyte dosage.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: SLo Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Shizuoka Prefecture Experimental Animal Agricultural Cooperative Association (Nokyo)
- Age at study initiation: 7 weeks
- Weight at study initiation: 240 grams for males and 180 grams for females
- Fasting period before study: 15 to 17 hours
- Housing: Plastic cages (Aircon B from Clea Japan, Inc) with wood shavings on the floor of the cages
- Diet (e.g. ad libitum): The rats were provided unlimited quantities of feed ("MF Rat Feed" from Oriental Yeast Co. Ltd)
- Water (e.g. ad libitum): The rats were provided unlimited quantities of water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 + 1°C
- Humidity (%): 60 + 10%
- Air changes (per hr): 12 changes of air per hour

Route of administration:

oral: gavage

Vehicle:

other: Suspension in 5 % gum arabic

Doses:

Three dose levels of the analyte were administered (3, 6 or 12 g/kg), based on the maximum physical intake capacity of rats as determined by previous experimentation. As a control group , one group was given 4 mL/100 g (weight) of 5 % gum arabic, the same quantity as the group that received the maximum analyte dosage.

No. of animals per sex per dose:

10 males and 10 female per dose group.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: The general condition and health condition of the rats were observed for 7 days after administration. The animals weight was measured every day for 7 daya after administration.
- Necropsy of survivors performed: yes - all the animals were dissected after the end of the 7 days, and observations were made of their various organs.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 12 other: g/kg bw

Based on:

test mat.

Mortality:

No cases of deaths occurred in any of the test groups.

Clinical signs:

other: Males: No noteworthy toxic effects were observed in any of the test groups, although there was a temporary decrease in spontaneous exercise and a slight pilometer reflex after administration of the analyte. Females: As was true with the male rats, there

Gross pathology:

No abnormalities were observed during dissection.

Other findings:

Males:
There were no observations of unusual appearance or behavior in any of the test groups throughout the observation period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The analyte test material was administered suspended in 5 % gum arabic by gavage to SLo Wistar rats at the following dose levels:

3, 6 or 12 g/kg

The LD50 was determined to be >12 g/kg.

Executive summary:

After one week of acclimatisation, experiments were carried out on 7-week old rats with average bodyweights of 240 grams for males and 180 grams for females.

The rats were divided into four groups, each composed of 10 males and 10 females.

Three dose levels of the analyte were administered (3, 6 or 12 g/kg), based on the maximum physical intake capacity of rats as determined by previous experimentation. As a control group , one group was given 4 ml/100 g (weight) of 5% gum arabic, the same quantity as the group that received the maximum analyte dosage.

All of the animals were dissected after the end of the 7 days and observations were made of their various organs.

No cases of deaths occurred in any of the test groups.

Males:

No noteworthy toxic effects were observed in any of the test groups, although there was a temporary decrease in spontaneous exercise and a slight pilometer reflex after administration of the analyte.

Females:

As was true with the male rats, there were no toxic effects observed in any of the test groups, although there was the same temporary decrease in spontaneous exercise and slight pilometer reflex.

Weight gain trends were normal.

No abnormalities were observed during dissection.

There were no observations of unusual appearance or behavior in any of the test groups throughout the observation period.

The LD50 was determined to be >12 g/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

12 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

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

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%

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.

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

670 mg/m³ air

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:

Study conducted between April 1988 and June 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.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

other: modified procedure described by Noakes and Sanderson (similar to standard acute method)

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Ltd, Manston Road, Margate, Kent
- Age at study initiation: Males were between 48 to 50 days old and females were between 56 to 65 days old
- Weight at study initiation: 278 g to 342 g for Males and 211 g to 267 g for Females
- Fasting period before study: not stated in report
- Housing: Rats were housed in pairs by sex and in steel mesh cages
- Diet (e.g. ad libitum): Free acess to Modified Expanded S.Q.C Rat and Mouse Diet No. 1
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 22 deg C
- Humidity (%): 44 to 54%
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours light followed by 12 hours of darkness

IN-LIFE DATES: From: Day of dosing (day 1) To: Day of sacrifice (day 14)

Type of coverage:

occlusive

Vehicle:

other: moistened with 0.5% sodium carboxymethyl in distilled water.

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 cm by 10 cm
- Type of wrap if used: aluminium foil (held in place by an encircling band of waterproof plaster).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin was washed with soap and water to remove residual test material and then rinsed with water and dried.
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes, test material was moistened with 0.5% w/v solution sodium carboxymethylcellulose in distilled water and applied to the shaved area at a dose level of 2100 mg/kg.

Duration of exposure:

24 hours

Doses:

0 (control) and 2100 mg/kg

No. of animals per sex per dose:

5 males and 5 females were tested at both the 0 and 2100 mg/kg dose range (e.g. 20 animals in total)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical signs and behaviour frequently on the day of treatment, at least once each morning and afternoon on working days thereafter and at leaast once each other day. Bodyweights were recorded immediately prior to treatment on Day 1, on Day 8 and immediately prior to termination on Day 15.

- Necropsy of survivors performed: yes - all animals were killed by CO2 asphyxiation on Day 15 and subjected to gross post-mortem examination for external abnormalities and for abnormalities of the thoracic and abdominal viscera.
- Other examinations performed: skin irritation - after removal of the plaster, skin treatment sites were examined daily for evidence of skin irritation.

Statistics:

The significance of difference between bodyweight change of control and test groups was estimated by the two sample test of Dunnett.

Preliminary study:

Range finding with 1 male and 1 female: no evidence of toxicity or skin irritation

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 100 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no treatment related clinical signs during the study.

Gross pathology:

There were no abnormal findings

Other findings:

Skin irritation: There was no evidence of skin irritation.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In both sexes, the acute dermal LD50 was greater than 2100 mg/kg bw.

Executive summary:

The purpose of the study is to determine the acute dermal toxicity of techncial GEL-ALL-MD to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg Technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 100 mg/kg bw

Additional information

Acute oral:

After one week of acclimatisation, experiments were carried out on 7-week old rats with average bodyweights of 240 grams for males and 180 grams for females.

The rats were divided into four groups, each composed of 10 males and 10 females.

Three dose levels of the analyte were administered (3, 6 or 12 g/kg), based on the maximum physical intake capacity of rats as determined by previous experimentation. As a control group , one group was given 4 ml/100 g (weight) of 5% gum arabic, the same quantity as the group that received the maximum analyte dosage.

All of the animals were dissected after the end of the 7 days and observations were made of their various organs.

No cases of deaths occurred in any of the test groups.

Males:

No noteworthy toxic effects were observed in any of the test groups, although there was a temporary decrease in spontaneous exercise and a slight pilometer reflex after administration of the analyte.

Females:

As was true with the male rats, there were no toxic effects observed in any of the test groups, although there was the same temporary decrease in spontaneous exercise and slight pilometer reflex.

Weight gain trends were normal in all groups (male and female).

No abnormalities were observed during dissection in all groups (male and female).

There were no observations of unusual appearance or behavior in any of the test groups throughout the observation period.

The LD50 in rats was determined to be >12 g/kg.

Acute inhalation:

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 bodyweights, 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.

Acute Dermal:

The purpose of the study is to determine the acute dermal toxicity of techncial GEL-ALL-MD to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 mg/kg bw.

Justification for classification or non-classification

The substance does not meet the criteria for classification, under the CLP regulations, for acute toxicity via the oral, inhalation or dermal routes based on the results of an acute oral toxicity study, an acute inhalation study and an acute dermal toxicity study.

No adverse toxic effects were seen at the highest doses tested in any of the acute toxicity studies.

The LD₅₀ result of the acute oral toxicity study (>12 g/kw bw) and acute dermal toxicity study (>2100 mg/kg bw) are above the threshold LD₅₀ values for classification (<2000 mg/kg bw).

The LD₅₀ result in the acute inhalation study (>0.67 mg/l air) was greater than the maximum attainable concentration used in the study.

The substance is therefore not classified for acute toxicity.