Reaction mass of (1RS,2RS,7SR,8RS,9E)-9-Ethylidene-3-oxatricyclo [6.2.1.0(2,7)] undecane and (1RS,2RS,7SR,8RS,9Z)-9-Ethylidene-3-oxatricyclo [6.2.1.0(2,7)] undecane and (1RS,2SR,7SR,8SR,10E)-10-Ethylidene-3-oxatricyclo[6.2.1.0(2,7)] undecane and (1RS,2SR,7SR,8SR,10Z)-10-Ethylidene-3-oxatricyclo [6.2.1.0(2,7)] undecane

Endpoint summary

Description of key information

Oral: LD50= 5000 mg/kg bw, male rat, equiv. to OECD 401, Corven 1981
Dermal: LD50= > 5000 mg/kg bw, male/female rabbit, equiv. to OECD 402, Corven 1981

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Performed under GLP following a method similar to a recognised guideline; limited test material characeterisation.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised animal supplier.
- Age at study initiation: Not reported
- Weight at study initiation: 241 - 267 g
- Fasting period before study: 16-20 hours prior to doing.
- Housing: Test animals were housed 5/cage in suspended wire mesh cages.
- Diet (e.g. ad libitum): ad libitum except for 16-20 hours prior to doing.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article was administered orally, one time, by syringe and dosing needle on a g/kg basis.

Doses:

5.0 g/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 3-4 hours post dosing and once daily thereafter for 14 days for mortality, toxicity and pharmacological effects.
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

A total of 5 animals died (3 on day 1 and 2 on day 2).

Clinical signs:

other: Principal toxic manifestations included lethargy, ataxia, piloerection, ptosis and coma. Except for isolated instances of chromodacryorrhea and chromorhinorrhea, the survivors were normal from Day 3 to Day 14.

Gross pathology:

Necropsy of the deaths revealed abnormalities of the heart, lungs, gastrointestinal tract, kidneys and urinary bladder. Necropsies of the survivors
were normal.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The acute oral median lethal dose (LD50) of the test material in male Wistar rats was considered to be 5000 mg/kg body weight.

Executive summary:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain of rat. The study was performed under GLP and followed a method equivalent to OECD guideline 401. The test material was administered orally, after fasting for 16 -20 hours, once only by gavage. 10 male test animals were dosed at 5000 mg/kg body weight. Mortality and clinical signs were monitored during the study. All animals were subjected to gross necropsy after an observation period of 14 days.

Mortality occurred on Days 1 and 2 of the study. Principal toxic manifestations included lethargy, ataxia, piloerection, ptosis and coma. Except for isolated instances of chromodacryorrhea and chromorhinorrhea, the survivors were normal from Day 3 to Day 14. Necropsy of the deaths revealed abnormalities of the heart, lungs, gastrointestinal tract, kidneys and urinary bladder. Necropsies of the survivors VJere normal. The acute oral median lethal dose (LD50) of the test material in the male Wistar strain rat is 5000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information as a whole meets the tonnage driven information requirements of REACH.

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:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An acute dermal study performed under GLP and follows a method similar to an OECD guideline; limited test material characeterisation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: recognised animal source
- Age at study initiation: not reported
- Weight at study initiation: 2.1 - 2.8 kg
- Housing: The animals were housed 2/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet: Certified rabbit feed ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS: not reported

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdomen
- Type of wrap if used: The test article was covered with a gauze patch and gentle pressure was applied to the gauze to aid the distribution of the test article over the prepared site. The torso was wrapped with plastic which was secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): site wiped.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg

Duration of exposure:

24h

Doses:

5000 mg/kg

No. of animals per sex per dose:

2 males and 3 females.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test sites were scored for dermal irritation at 24 hours post dose and on Days 7 and 14 using the numerical Draize scale. Additional signs were described. The animals were observed daily for 14 days for mortality, toxicity and pharmacological effect. Body weights were recorded pretest and at termination in the survivors.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One test animal died on day 1.

Clinical signs:

other: Yellow nasal discharge, few feces, lethargy, piloerection and ptosis were noted in 2/4 survivors and 2/4 were generally normal throughout the study. Dermal reactions, generally slight on Day 1 and severe on Day 7, cleared in 3/4 animals by Day 14.

Gross pathology:

Necropsy was normal for 1/4 survivors. The other 3/4 animals had lung, intestinal or treated skin abnormalities.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the LD50 was determined to be > 5000 mg/kg and so the test material is not considerd to be toxic to New Zealand rabbits via the dermal route.

Executive summary:

The study was performed to assess the dermal toxcity of the test material to New Zealand White rabbit. The study was performed under GLP and followed a method similar to OECD 402 guideline. The test substance was evaluated in 5 New Zealand white rabbits. A dose of 5000 mg/kg test substance (undiluted), was applied to intact and abraded clipped skin site under a occlusive dressing for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. One rabbit died on Day 1. There were no predeath toxic signs or abnormalities at necropsy. Yellow nasal discharge, few feces, lethargy, piloerection and ptosis were noted in 2/4 survivors and 2/4 were generally normal throughout the study. Dermal reactions, generally slight on Day 1 and severe on Day 7, cleared in 3/4 animals by Day 14. Body weight changes were normal for 2/4 animals. One rabbit failed to gain and one animal lost weight. Necropsy was normal for 1/4 survivors. The other 3/4 animals had lung, intestinal or treated skin abnormalities. Under the conditions of this study the LD50 is considered to be greater than 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information as a whole meets the tonnage driven information requirements of REACH.

Additional information

Acute Oral:

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain of rat. The study was performed under GLP and followed a method equivalent to OECD guideline 401. The test material was administered orally, after fasting for 16 -20 hours, once only by gavage. 10 male test animals were dosed at 5000 mg/kg body weight. Mortality and clinical signs were monitored during the study. All animals were subjected to gross necropsy after an observation period of 14 days. Mortality occurred on Days 1 and 2 of the study. Principal toxic manifestations included lethargy, ataxia, piloerection, ptosis and coma. Except for isolated instances of chromodacryorrhea and chromorhinorrhea, the survivors were normal from Day 3 to Day 14. Necropsy of the deaths revealed abnormalities of the heart, lungs, gastrointestinal tract, kidneys and urinary bladder. Necropsies of the survivors were normal. The acute oral median lethal dose (LD50) of the test material in the male Wistar strain rat is 5000 mg/kg bodyweight.

Acute Dermal:

The study was performed to assess the dermal toxcity of the test material to New Zealand White rabbit. The study was performed under GLP and followed a method similar to OECD 402 guideline. The test substance was evaluated in 5 New Zealand white rabbits. A dose of 5000 mg/kg test substance (undiluted), was applied to intact and abraded clipped skin site under a occlusive dressing for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. One rabbit died on Day 1. There were no predeath toxic signs or abnormalities at necropsy. Yellow nasal discharge, few feces, lethargy, piloerection and ptosis were noted in 2/4 survivors and 2/4 were generally normal throughout the study. Dermal reactions, generally slight on Day 1 and severe on Day 7, cleared in 3/4 animals by Day 14. Body weight changes were normal for 2/4 animals. One rabbit failed to gain and one animal lost weight. Necropsy was normal for 1/4 survivors. The other 3/4 animals had lung, intestinal or treated skin abnormalities. Under the conditions of this study the LD50 is considered to be greater than 5000 mg/kg.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

The substance does not meet classification criteria under EU Directive 67/548/EEC for acute toxicity.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.