7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Endpoint summary

Description of key information

Two acute oral toxicity study reports are available.  The studies were conducted using male and female Crl:CD(SD)IGS BR and Sprague Dawley rats.  One of the studies conformed to the OECD guideline 401 (Acute Oral Toxicity).  In both instances, Celloxide 2021 was not classified as the LD50 values were at least 5000mg/kg.  
An acute inhalation study is available.  The rat was the test species. Based on the study results the test substance does not require classification. In an acute dermal toxicity study conforming to OECD Guideline 402,  rats were used as the test species.  The study indicated that the test substance should not be classified.

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:

21 May 1999 - 9 September 1999.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline study conforming to the relevant guidelines.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Cycloaliphatic Epoxy Resin ERL-4221

- Substance type: Not documented
- Physical state: Clear, colorless, viscous liquid
- Analytical purity: Not documented
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Certificate of Analysis dated 2 October 1999
- Lot/batch No.: 87068
- Expiration date of the lot/batch: Not documented

- Stability under test conditions: Test article stability data are being monitored as part of the test program and will be reported separately.
- Storage condition of test material: Original container at room temperature

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: Eight to nine weeks old (males) and nine to 10 weeks old (females)
- Weight at study initiation: 264 to 299 g (males) and 200 to 228 g (females)
- Fasting period before study: Food was withheld during the 18- to 20-hour period immediately prior to dosing and returned three to four hours after dosing.
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 ad libitum
- Water (e.g. ad libitum): Reverse osmosis treated municipal water
- Acclimation period: Minimum of seven days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8 - 22.3°C
- Humidity (%): 43.3-62.4%
- Air changes (per hr): Not documented
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: May 21, 1999 To: June 11, 1999

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Not applicable
- Amount of vehicle (if gavage): Not applicable
- Justification for choice of vehicle: Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

MAXIMUM DOSE VOLUME APPLIED: The dose volume was determined by dividing the dose levels of 2959 and 5000 mg/kg, by the specific gravity (1180 mg/mL). Individual doses of the test article were calculated based on body weights obtained just prior to dosing and dose levels of 2.51 and 4.24 ml/kg for the 2959 and 5000 mg/kg groups, respectively.

DOSAGE PREPARATION (if unusual):
A sufficient amount of test article, agitated prior to use, was transferred from the original container to a labelled storage container. A stir bar was added, and the test article was stirred continuously throughout use.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not applicable

Doses:

2959 and 5000 mg/kg

No. of animals per sex per dose:

20 animals (10 male and 10 female)
Groups of five male and five female were administered either 2959 or 5000 mg/kg dose levels.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed at approximately 1, 3 and 4 hours post-dosing on day 0 and once daily thereafter for 14 days. Body weights were obtained and recorded on study days -1, 0 (initiation), 7 and 14 (termination). In addition, decedents were weighed as soon as they were found.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; other: The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.

Statistics:

No information provided.

Preliminary study:

Not applicable.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 959 - < 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Three males and two females died within six days of dosing. Mortality was 0/10 and 5/10 for the 2959 and 5000 mg/kg groups, respectively. Single deaths occurred on days 2, 3, 4, 5 and 6.

Clinical signs:

other: other: Clinical findings were noted in both dose groups during the first week of the study. Four animals in the 2959 mg/kg group and all animals in the 5000 mg/kg group were noted with various discolored areas due to discharges/excretions [described as w

Gross pathology:

Three animals (one male and two females) that died were noted with dark red contents in the stomach and/or a distended stomach. Various red and/or yellow matting around the eyes, nose, anogenital and/or urogenital area was noted for these animals that died. There were no other necropsy findings for animals found dead. One male from the 5000 mg/kg group was noted with capsular scarring of the spleen at the scheduled necropsy. There were no other findings for any examined tissues at the scheduled necropsy.

Other findings:

No additional information

No additional information

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results of this study indicate that the LD50 of Cycloaliphatic Epoxy Resin ERL-4221 was found to be approximately 5000 mg/kg in fasted male and female albino rats when administered once orally via gavage. Based on these results, it was not necessary to classify the test substance according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Executive summary:

In a study conducted by Kern (1999), the acute oral toxicity of Cycloaliphatic Epoxy Resin ERL-4221 was evaluated in a single-dose study in rats. The test article was administered once orally via gavage to groups of five male and five female fasted albino rats at dose levels of 2959 and 5000 mg/kg. The animals were observed at regular intervals for up to 14 days following administration to ascertain any changes in body weight or clinical behaviour. At termination of the study after 14 days, the animals were necropsied and any changes in the major organs was recorded.

3 males and 2 females in the 5000 mg/kg group died within six days of dosing. Mortality was 0/10 and 5/10 for the 2959 and 5000 mg/kg groups, respectively. Clinical findings were noted in both dose groups during the first week of the study with observations including various discolored areas due to discharges/excretions, hypoactivity and/or impaired muscle coordination. Animals in the higher dose group were noted with decreased defecation, decreased urination, labored respiration and/or convulsions. All animals appeared normal by day 6 and throughout the remainder of the study. Three animals that died were noted with gastric abnormalities. There were no other internal gross necropsy findings for animals found dead.

The LD₅₀ of Cycloaliphatic Epoxy Resin ERL-4221 was found to be approximately 5000 mg/kg in fasted male and female albino rats

when administered once orally via gavage. Since the median lethal dose estimate was much higher than the test guideline limit, it was not necessary to classify the test substance according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Reliable

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:

18 May 2010 to 9 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary Guideline Study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

yes

Remarks:

Body weight was not recorded on Day 7, however additional measurements were made. This will not affect the validity of the study.

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

-Name of test material (as cited in study report): Celloxide 2021P
- Physical state: Yellow liquid
- Analytical purity: 96.48%
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: 6th April 2010
- Lot/batch No.: CELP-AD-038
- Expiration date of the lot/batch: 7th July 2010
- Stability under test conditions: Not documented
- Storage condition of test material: When not in use, the test article was stored in a sealed container, at 15-25ºC.

Species:

rat

Strain:

other: HsdHanTM:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Bicester, UK
- Age at study initiation: approximately 11 weeks old
- Weight at study initiation: males weighed between 238 and 244 g, females weighed between 203 and 217 g
- Fasting period before study: Not documented
- Housing: The animals were housed in groups of three/sex. European softwood bedding was provided weekly to each cage. The animals were provided with wooden aspen chew blocks and rodent retreats.
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No 1, Expanded ad libitum
- Water (e.g. ad libitum): Mains water was provided ad libitum via water bottles.
- Acclimation period: 8 days. Animals were acclimatised to the restraint procedures for 3 consecutive days prior to the exposure, for successive periods of 1, 2 and 4 hours.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): minimum of 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark.

IN-LIFE DATES: From: 18 May 2010 To: 9 June 2010

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Restraint tubes
- Exposure chamber volume: 40L
- Method of holding animals in test chamber: Not documented
- Source and rate of air: 25L/min
- Method of conditioning air: An aerosol of the test article, Celloxide 2021P, was generated using a Jet atomiser into a flow-through (nose-only) exposure chamber (volume approximately 40 L) continuously for four hours.
- System of generating particulates/aerosols:
- Method of particle size determination: The particle size distribution of the aerosol was measured gravimetrically using a Marple Series 290 cascade impactor by sampling the aerosol from inside the chamber at a flow rate of 2L/min. The weight of test article collected on each substrate was used to calculate the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD).
- Treatment of exhaust air: No information provided
- Temperature, humidity, pressure in air chamber: Temperature: 20.2°C
Humidity: 21.9%
Oxygen Concentration: 19% (v/v)

TEST ATMOSPHERE
- Brief description of analytical method used: The chamber aerosol concentration was sampled at a flow rate of 1 L/minute on to weighed glass fibre filters. Using the collected weight and volume of air sampled, the gravimetric chamber aerosol concentration was calculated. Filter samples were collected from a sampling port representative of the animals breathing zone.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): Not documented
- Concentration of test material in vehicle (if applicable): Not documented
- Justification of choice of vehicle: Not documented
- Lot/batch no. (if required): Not documented
- Purity: Not documented

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Mean MMAD: 3.09 μm and GSD: 2.54

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

>= 4 h

Concentrations:

4.56 to 5.50 mg/L

No. of animals per sex per dose:

3 per sex per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed at the beginning and the end of the working day to ensure the animals were in good health. All animals were observed daily for signs of ill health or overt toxicity. In addition, each animal was given a weekly detailed physical examination as part of the daily dosing observations. The animals were observed pre-exposure and during dosing at hourly intervals, commencing 30 minutes after the start of exposure, until the end of the working day. An observation was performed when the animals were returned to the cage (approximately 10 minutes after the end of exposure), then once daily during the remainder of the study. Individual body weights were recorded for all animals before and after exposure on Day 1 and on Days 2, 3, 4, 8, 14 and 15. As one female had not returned to the pre-exposure body weight, all females were weighed on Day 5.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No additional observations

Statistics:

No information provided

Preliminary study:

Not relevant

Sex:

male/female

Dose descriptor:

other:

Effect level:

>= 5.19 mg/L air

Based on:

not specified

Exp. duration:

4 h

Remarks on result:

other: Inhalation exposure to Celloxide 2021P at 5.19 mg/L was well tolerated. No animals died or showed any persistent clinical signs attributable to the test article, and there were no major effects on body weight.

Mortality:

There were no premature decedents during this study. No rats died as a result of exposure to Celloxide 2021P at dose range of 4.56 - 5.50 (mean 5.19 mg/L)

Clinical signs:

other: There were no clinical observations for any animal during the 4-hour exposure or up to 4.5 hours post dose. At the end of the working day (approximately 6 hours post exposure), 2 female animals were lethargic, and the 3rd female was ataxic with tachypnoea

Body weight:

All animals lost body weight during exposure. Males regained their pre-exposure body weights by Day 3 or 4. The females returned to their pre-exposure body weight by Day 4 or 5.

Gross pathology:

There were no findings following macroscopic examination at necropsy.

Other findings:

No additional information

No additional information

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, inhalation exposure to Celloxide 2021P at 5.19 mg/L was well tolerated as there were no mortalities observed and no abnormal clinical signs attributable to the test substance. Based on these results, classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC was not warranted.

Executive summary:

In a study conducted by Leighton (2010), the test substance Celloxide 2021P, was evaluated for its ability to induce toxicity when tested in male and female Wistar rats via nose only inhalation for a period of 4 hours. The concentration of doses was in the range 4.56 - 5.50mg/L (mean of 5.19mg/L).

Following administration of the test substance, there were no mortalities observed. Some initial weight loss was evident in both males and females post dosing, however, all animals had returned to their pre-exposure body weight by day 5 post-exposure. Approximately 6 hours post exposure), 2 female animals were lethargic, and the 3rd female was ataxic with tachypnoea, exophthalmus and trance like behaviour. On Day 2, all females were unkempt and the 3rd female had exopthalmus. There were no other clinical signs considered to be related to treatment.

Inhalation exposure to Celloxide 2021P at dose range of 4.56 - 5.50 (mean 5.19 mg/L) was well tolerated.

Under the conditions of the study, inhalation exposure to Celloxide 2021P at 5.19 mg/L was well tolerated as there were no mortalities observed and no abnormal clinical signs attributable to the test substance. Based on these results, classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC was not warranted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 000 mg/m³ air

Quality of whole database:

reliable

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:

17 May 2010 to 8 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline compliant study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Celloxide 2021P
- Substance type: Not documented
- Physical state: Yellow liquid
- Analytical purity: 96.48%
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: CELP-AD-038
- Expiration date of the lot/batch: 7th July 2010
- Stability under test conditions: Not documented
- Storage condition of test material: Stored in a sealed container, at room temperature and in the dark.

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK. Ltd., Bicester.
- Age at study initiation: 8 - 9weeks old
- Weight at study initiation: Males: 242 - 277g
Females: 175 - 204g
- Fasting period before study:
- Housing: During the acclimatisation period, up to five rats of the same sex were accommodated in cages. From the day prior to dosing, each rat was housed individually in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing. Bedding was provided on a weekly basis to each cage by use of clean Aspen wood chips.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1 available freely to animals at all times.
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 45 - 65%
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: From: 17 May 2010 To: 8 June 2010

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsum of the rat
- % coverage: 10% The total surface area (cm2) for each animal was calculated according to the largest animal in each group using the following formula:
Surface area (cm2) = K x body weight (g)2/3 (where K = 9) {Spector, W.S., Handbook of Biological Data, W.B. Sanders Co., 1956; 175.}

- Type of wrap if used: A dense gauze patch was placed over the treated skin and retained in place by an elasticated, open-weave, adhesive compression bandage. This was wrapped securely around the torso of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: Approximately 24 hours after the start of exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg Dose volume 1.693 mL/kg bw adjusted for specific gravity of 1.1816 g/mL to achieve 2000 mg/kg bw dose level
- Concentration (if solution): applied as supplied without dilution
- Constant volume or concentration used: Constant volume
- For solids, paste formed: Not relevant

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

In the preliminary test, 2 test animals (1 per sex) were used.
In the definitive test, 8 animals were used (4 per sex), meaning a total of 10 animals (5 per sex) were treated in the study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on the day prior to dosing and on days 1, 4, 8 and 15. Clinical observations were made once within half an hour of dosing, four times within four hours of dosing, twice daily on Days 2, 3 and 4 and once daily from the fifth day of the observation period. The condition of the dermal test site was recorded following removal of the dressing on Day 2 and once daily thereafter for the duration of the study period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology. Dermal reactions assessed using standard modified Draize evaluation schema.

Statistics:

Not relevant - median lethal dose determined directly from mortality incidence.

Preliminary study:

Not relevant

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study

Clinical signs:

other: other: There were no clinical signs of reaction to treatment. No dermal reactions were observed.

Gross pathology:

No macroscopic changes were noted at necropsy.

Other findings:

No additional information provided.

No additional information

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute median lethal dose of Celloxide 2021P to rats was found to exceed 2000 mg/kg. Based on the result of this study, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Executive summary:

In a study conducted by Dreher (2010), the test substance, Celloxide 2021P, was investigated to determine its ability to induce dermal toxicity following a single semi-occluded topical application to the test species, male and female Wistar rats. The dorsum of a group of 5 male and 5 female rats was clipped and 2000mg/kg of the test substance was applied, undiluted, to this test area. The treated area of the dorsum was covered by a semi-occlusive dressing for 24 hours. The animals were observed for a 14 day observation period. At sacrifice on Day 15, a full necropsy was performed.

No animal died and there were no clinical signs of reaction to treatment. No abnormal dermal changes were noted at the test sites. All rats gained weight during the first and second weeks of the study, except for two females which lost weight during the second week of the study but showed an overall increase in body weight over the observation period. There were no macroscopic changes apparent at necropsy.

Under the conditions of this study, the acute median lethal dose of Celloxide 2021P to rats was found to exceed 2000mg/kg. Based on the result of this study, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Reliable

Additional information

Acute Oral Toxicity:

In the study conducted by Buch (1981), the acute oral toxicity of Celloxide 2021 was investigated in groups of fasted male and female rats of the Charles River CD strain at dosages within the range 3500 - 5500 mg/kg. The test compound was administered at a variable volume-dosage in maize oil on Day 1. Mortality and signs of reaction to treatment were recorded during a 14 -day period of observation.

Under the conditions of this study the acute oral median lethal dosage (LD50) was greater than 5000 mg/kg.

In the key study conducted by Kern (1999), the acute oral toxicity of Cycloaliphatic Epoxy Resin ERL-4221 was evaluated in a single-dose study in rats. The test article was administered once orally via gavage to groups of five male and five female fasted albino rats at dose levels of 2959 and 5000 mg/kg.The animals were observed at regular intervals for up to 14 days following administration to ascertain any changes in body weight or clinical behaviour. At termination of the study after 14 days, the animals were necropsied and any changes in the major organs were recorded.

3 males and 2 females in the 5000 mg/kg group died within six days of dosing. Mortality was 0/10 and 5/10 for the 2959 and 5000 mg/kg groups, respectively. Clinical findings were noted in both dose groups during the first week of the study with observations including various discoloured areas due to discharges/excretions, hypoactivity and/or impaired muscle coordination. Animals in the higher dose group were noted with decreased defecation, decreased urination, laboured respiration and/or convulsions. All animals appeared normal by day 6 and throughout the remainder of the study. Three animals that died were noted with gastric abnormalities. There were no other internal gross necropsy findings for animals found dead.

The LD₅₀ of Cycloaliphatic Epoxy Resin ERL-4221 was found to be approximately 5000 mg/kg in fasted male and female albino rats when administered once orally via gavage.

The study conducted by Kern (1999) was considered to be the key study as it was a proprietary guideline study which conformed to OECD Guideline 401 and was conducted in accordance to GLP.

Acute Inhalation Toxicity:

In a study conducted by Leighton (2010), the test substance Celloxide 2021P, was evaluated for its ability to induce toxicity when tested in male and female Wistar rats via nose only inhalation for a period of 4 hours. The concentration of doses was in the range 4.56 - 5.50mg/L (mean of 5.19mg/L).

Following administration of the test substance, there were no mortalities observed. Some weight loss was evident in both males and females post dosing, however, all animals had returned to their pre-exposure body weight by day 5 post-exposure. Approximately 6 hours post exposure), 2 female animals were lethargic, and the 3rd female was ataxic with tachypnoea, exophthalmus and trance like behaviour. On Day 2, all females were unkempt and the 3rd female had exopthalmus. There were no other clinical signs considered to be related to treatment.

Inhalation exposure to Celloxide 2021P at dose range of 4.56 - 5.50 (mean 5.19 mg/L) was well tolerated.

Under the conditions of the study, inhalation exposure to Celloxide 2021P at 5.19 mg/L was well tolerated as there were no mortalities observed and no abnormal clinical signs attributable to the test substance. Based on these results, classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC was not warranted.

Acute Dermal Toxicity:

In a study conducted by Dreher (2010), the test substance, Celloxide 2021P, was investigated to determine its ability to induce dermal toxicity following a single semi-occluded topical application to the test species, male and female Wistar rats. The dorsum of a group of 5 male and 5 female rats was clipped and 2000mg/kg of the test substance was applied, undiluted, to this test area. The treated area of the dorsum was covered by a semi-occlusive dressing for 24 hours. The animals were observed for a 14 day observation period. At sacrifice on Day 15, a full necropsy was performed.

No animal died and there were no clinical signs of reaction to treatment. No abnormal dermal changes were noted at the test sites.All rats gained weight during the first and second weeks of the study, except for two females which lost weight during the second week of the study but showed an overall increase in body weight over the observation period. There were no macroscopic changes apparent at necropsy.

Under the conditions of this study, the acute median lethal dose of Celloxide 2021P to rats was found to exceed 2000mg/kg. Based on the result of this study, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Justification for selection of acute toxicity – oral endpoint
Limit test showing no indication of acute oral toxicity

Justification for selection of acute toxicity – inhalation endpoint
Limit test showing no indication of acute inhalation toxicity

Justification for selection of acute toxicity – dermal endpoint
Limit test showing no indication of acute dermal toxicity

Justification for classification or non-classification

Based on the results of the oral study outlined above, the test substance, Cycloaliphatic Epoxy Resin ERL-4221 did not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Based on the results of the dermal study outlined above, the test substance, Celloxide 2021P did not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Based on the results of the inhalation study outlined above, the test substance, Celloxide 2021P did not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.