6-glycidyloxynapht-1-yl oxymethyloxirane

Endpoint summary

Description of key information

The Acute oral toxicity to rats of EPICLON EXA 4032 was performed to assess the toxicity following a single oral dose and to determined the LD50.
The Dermal toxicity to rats of EPICLON EXA 4032 was performed to assess the toxicity following a single dermal dose and to determined the LD50.

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:

05.06.1986 to 19.06.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna UK Ltd., (fromely Hacking and Churchill Ltd.), Cambridgeshire, England.

They were in a weight range of 109 to 150 g prior to dosing (Day 1) in the main study and approximately four to six weeks of age. All rats were acclimated to the experimental environment for a period of 7 days prior to the start of the main study.

The rats were allocated to cages within the treatment group. They were housed in groups by sex in metal cages with wire mesh floors. A standard laboratory rodent diet (labsure LAD 1) and water were provided ad Libitum. The batch of diet used for the study was analysed for certain chemical and microbiological contaminants. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.

The mean daily minimum and maximum temperatures of the animal room were 22°C and 25°C respectively and the mean daily relative humidity value was 54%. The rate of air exchange was maintained at approximately 15 air changes/hour. lighting was controlled by means of a time switch to 12 hours artificial in each 24 hour period.

Each animal was identified by cage number and ear punching.
Each cage was identified by a coloured label displaying the dose level, study schedule number and the initials of the study Director.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Preliminary study:
-A trial test was carried out to establish a dosing regimen using groups of two male and two female rats at two dose levels of 1.0 and 5.0 g/kg bodyweight.

Main study:
-A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.

Doses:

-Preliminary study: 1.0 and 5.0 g/kg bodyweight
-Main study: 2.0 g/kg bodyweight.

No. of animals per sex per dose:

-Preliminary study: 2 males and 2 females rats.
-Main study: ten rats (5 males and 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing; then at frequent intervals fot the remainder of Day1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observations was at approximately 16.30 hours on weekdays or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation.
The animals on the preliminary study were observed for 5 days (dose 1.0 g/kg) or 7 days (dose 5.0 g/kg). Those on the main study were observed for 14 days after dosing.
Individual bodyweights of rats on Day 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Preliminary study:

A trial test was carried out to establish a dosing regimen using groups of two male and two female rats at two dose levels of 1.0 and 5.0 g/kg bodyweight. Losses of bodyweight were recorded on Day 8 for each of the three rats surviving administration of Epiclon EXA-4032 at 5.0 g/kg. Autopsyof these animals on Day 8 revealed gross thickening of the gatsric epithelium and adhesions of the stomach to the abdominal wall and adjacent viscera. Thus, although the preliminary study indicated the acute median lethal oral dose of Epiclon EXA-4032 was in the region of 5.0 g/kg, it was inappropriate to establish the LD50with greater precision on humane grounds. The study was completed by demonstrating that the lethal threshold dose (acute lethal dose) of Epiclon EXA-4032 was greater than 2.0 g/kg bodyweight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral dose of EPICLON EXA-4032 at 2.0 g/kg bodyweight.

Clinical signs:

other: Signs of reaction to treatment seen in all rats during the first three days of the observation period were pilo-erection and abnormal body carriage (hunched posture). All rats showed pallor of the extremities between days 8 and 11. Recovery, as judged by

Gross pathology:

Terminal autopsy revealed thickening or ulceration of the epithelium of the non-glandular zone of the stomach and adhesions of the stomach to the diaphragm, adjacent viscera and or the abdominal wall.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

In conclusion, the acute lethal oral dose to rats of EPICLON EXA-4032 was found to be greater than 2.0g/kg bodyweight.
LD50>2.0 g/kg bodyweight.

Executive summary:

This study was designed to assess the toxicity following a single oral dose and to determined the LD50.

The LD50 of EPICLON EXA-4032 was determined and the experimental procedure was based on the Testing Guidelines as given in Federal Register Vol.50 N°. 188, PartII dated 27 September 1985.Section 798.1175 -Acute Oral Toxicity.

For this experiment, a preliminary study was done to establish a dosing regimen using groups of 2 male and 2 female rats at 2 doses levels of 1.0 and 5.0 g/kg.

For the main study, a group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight..

The dose volume of the etst substance was administred to each rat using a syringue and plastic catheter and te viscosity of the test substance prevented it's administartion in the undiluted state.

In conclusion, the acute lethal oral dose to rats of EPICLON EXA-4032 was found to be greater than 2.0g/kg bodyweight.

LD50>2.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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:

06.02.1986 to 08.02.1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline performed under GLP

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of male and female CFY (Sprague-Dawley origin) rats were obtained from Interfauna U.K. Ltd., Huntingdon, Cambridgeshire, England. They were in a weight range of 208 to 251 g prior to dosing (Day1) and approximately six to eight weeks of age. All the rats were acclimated to the experimental environment for a period of not less than 5 days prior to the start of the study.
The rats were allocatex to ages within the treatment groups. They were housed individually in metal cages with wire mesh floors. A standard laboratory rodent diet (Labsure LAD1) and water were provided ad libitum. The batch of diet used for the study was analysed for certain chemical and microbiological contaminants.
Results of routine chemical examination of water at source (Grafham Final Water) as conducted by the Anglian Water Authority, are made available toHuntingdon Research Centre.
The mean daily minimum and maximum temperatures of the animal room were 22°C and 26°C respectively and the mean daily relative humidity value was 56%. The rate of air exchange was maintained at approximately 15 air changes/hour. Lighting was controlled by means of a time switch to 12 hours artificial light in each 24 hour period.
Each animal was identified by cage number and ear punching.
Each cage was identified by a coloured label dispalying the dose level, study schedule number and the initials of the study Director.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used.
The test substance was applied by spreading it evenly over the prepared skin. The treated area was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.
At the end of the 24-hours exposure period, the dressings were carefully removed and the treated area of skin decontamined by washing in alcohol and/or warm (30°-40°) water and blotting dry with absorbent paper.

Duration of exposure:

The duration of exposure is 24 hours.

Doses:

2.0 g/kg in an attempt to demonstrate the low toxicity of this treatment regime.
Study was completed by establishing the lethal threshold dose (Acute lethal dose) of the test substance.Rta were treated at dose of 0.4 and 1.0 g/kg.

No. of animals per sex per dose:

-One group of ten rats (5 males and 5 females) was dosed at 2.0 g/kg.
-Two groups of ten rats (5males and 5 females)were treated at doses of 0.4 g/kg and 1.0 g/kg.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 or 22 days.
- Frequency of observations and weighing:
Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1.
On subsequent days the animals were observed at least once in the morning and again at the end of the experimentalday. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation.
- Necropsy of survivors performed: yes
Surviving animals in the study were killed on Day 15 or 22 by cervical dislocation. All animals that died during the study and those killed on Days 15 or 22 were subjected to a macroscopic post mortem examination wich consisted of opening appearance of abnormal organs when present was recorded.
- Other examinations performed: clinical signs,Mortality,Dermal reactions body weight,Terminal autopsy.

Sex:

female

Dose descriptor:

LD50

Effect level:

< 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Three of the female rats dosed at 2.0 g/kg were found dead on days 8, 10 and 16. There were no deaths among the males rats at any dose level or among female rats dosed at 0.4 or 1.0 g/kg.

Clinical signs:

other: There were no clinical signs of a reaction to treatment until Day 5 or, at the lowest dose-level, until Day 9. The most common responses were: -Abnormal body carriage ( hunched posture) among rats dosed at 0.4 g/kg and in all rats given higher doses. -Pil

Gross pathology:

Autopsy of rats that died revealed geseous distension of the small and large intestines of 2 animals and single cases of abnormal fluid in the stomach and large intestine, abnormal fluid in the stomach, presence of white, raised areas on the non-glandular zone of the stomach and a small spleen.
Each of the rats that died lost more than 30% of bodyweight between tha day of dosing and death.

Other findings:

Slight or well-defined erythma was observed at the sites of application of Epiclon EXA 4032 upon removal of the occlusive dressing on Day 2.
Signs of dermal irritation became more marked until by Day 6 the majority of ratsshowed well-defined or moderate-to-severe erythema in association with slight, well-defined or moderate oedema.
Dermal inflammation resolved completely by Day 15.
A slight discolouration of the treated skin of all rats dosed at 0.4 or 1.0 g/kg was observed from Day 2 but had disappeared by Day 5.
Areas of herdening, a dry appearance of the treated skin, cracking or sloughing were observed in many animals from Day 7 but resolved before termination.

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

In conclusion, the acute lethal dermal dose to rats of Epiclon EXA 4032 was found to be between 1.0 g/kg bodyweight and 2.0 g/kg body weight.

Executive summary:

This study was designed to assess the toxicity following a single dermal dose and to determined the LD50.

The LD50 of EPICLON EXA-4032 was determined and the experimental procedure was based on the Testing Guidelines as given in Federal Register Vol.50 N°. 188, PartII dated 27 September 1985.Section 798.1100 -Acute Dermal Toxicity.

For this experiment, a preliminary study was done to establish a dosing regimen using groups of 5 male and female rats at 1 dose levels of 2.0 g/kg bodyweight.

For the main study, a group of ten rats (five males and five females) was treated at 0.4 or 1.0 g/kg bodyweight..

The dose of the etst substance was administred to each rat by spreading (type of coverage:occlusive)

In conclusion, the acute lethal dermal dose to rats of EPICLON EXA-4032 was found to be 1.0>LD50>2.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Additional information

This study was designed to assess the toxicity following a single oral dose and to determined the LD50.

The LD50 of EPICLON EXA-4032 was determined and the experimental procedure was based on the Testing Guidelines as given in Federal Register Vol.50 N°. 188, PartII dated 27 September 1985.Section 798.1175 -Acute Oral Toxicity.

For this experiment, a preliminary study was done to establish a dosing regimen using groups of 2 males and 2 females rats at 2 doses levels of 1.0 and 5.0 g/kg.

For the main study, a group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight..

The dose volume of the etst substance was administred to each rat using a syringue and plastic catheter and te viscosity of the test substance prevented it's administartion in the undiluted state.

In conclusion, the acute lethal oral dose to rats of EPICLON EXA-4032 was found to be greater than 2.0g/kg bodyweight.

LD50>2.0 g/kg bodyweight.

Then a study was designed to assess the toxicity following a single dermal dose and to determined the LD50.

The LD50 of EPICLON EXA-4032 was determined and the experimental procedure was based on the Testing Guidelines as given in Federal Register Vol.50 N°. 188, PartII dated 27 September 1985.Section 798.1100 -Acute Dermal Toxicity.

For this experiment, a preliminary study was done to establish a dosing regimen using groups of 5 male and female rats at 1 dose levels of 2.0 g/kg bodyweight.

For the main study, a group of ten rats (five males and five females) was treated at 0.4 or 1.0 g/kg bodyweight..

The dose of the etst substance was administred to each rat by spreading (type of coverage:occlusive)

In conclusion, the acute lethal dermal dose to rats of EPICLON EXA-4032 was found to be 1.0>LD50>2.0 g/kg bodyweight.

Justification for classification or non-classification

- oral toxicity:

Based on the above stated assessment of the acute oral toxicity of 1,6-Dihydroxynaphthalene diglycidyl ether-

, the substance does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according toCLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.

- dermal toxicity:

Based on the above stated assessment of the acute dermal toxicity of 1,6-Dihydroxynaphthalene diglycidyl ether-

the substance does need to be classified R21: Harmful in contact with skin according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and Acute Toxicity - Dermal Cat 4, H312 Harmful in contact with skin accordingCLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.