4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane

Endpoint summary

Description of key information

Study conducted according to OECD test guideline 401,male and female rats (5/sex/group) were treated with 2000 mg/kg bw of the test item by oral gavage, result: not classified

Study conducted according to OECD test guideline 402,groups of young adult Wistar rats (3/sex) were dermally exposed to Trioxabicyclooctan (100 % a.i) in 0.9% NaCl (750 mg/mL) for 24 hours at dose of 2000 mg/kg bw, result: not 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:

June 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Mol:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mollegaard Breeding Centre Ltd, Ejby, DK-4623 Ll. Skensved.
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 144-151 g
- Fasting period before study: 18 h
- Housing: The rats were individually ear-tagged and kept in Macrolone cages Type III (42 x 26 x 15 cm) 2 or 3 to a cage,· males and females separated. The bedding was softwood sawdust "Spanvall' Special White 11 from Spanvall Ltd, Jorlose, DK-4490 Jerslev.
- Diet (e.g. ad libitum): ad libitum, complete rodent diet ."Altromin 1314" from Chr. Petersen Ltd, DK-4100 Ringsted
- Water (e.g. ad libitum): tap water acidified with hydrochloric acid to pH 2.5, ad libitum
- Acclimation period: None

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/- 2
- Humidity (%): 55+/-15
- Air changes (per hr): 6
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: 1, 3 and 6 hours after administration and thereafter daily; weighing on day 0, 7, 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Since no rats died of the treatment the oral LD50 must exceed 2000 mg ",4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane"/kg b. wt.. According to Regulation (EU) No. 1727/2008 (CLP) the substance does not need to be classified with respect to acute oral toxicity.

Executive summary:

In an acute oral toxicity study according to OECD test guideline 401 (1987), groups of fasted, Wistar rats (5/sex) were given a single oral dose of 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane in water at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Females/Males > 2000 mg/kg bw

 

After single oral administration of 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane at 2000 mg/kg bw to male and female rats (5/sex/group) sedation and piloerection were found as clinical signs. At autopsy, no gross pathological organ changes were observed.

4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane is of LOW Toxicity based on the LD50 in female and male Wistar rats, thus, 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane is not classified for acute oral toxicity according to Regulation (EU) No. 1272/2008 (CLP).                                                                          

 

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:

2002-02-18 to 2002-06-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Shoe: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: not specified
- Weight at study initiation: males: 262-265 g; females: 198-209 g
- Housing: individually in conventional cages
- Diet (e.g. ad libitum): pell. Ssniff M-H ad libitum 24 hours per day
- Water (e.g. ad libitum): demineralized, acidified water, pH 2-3 ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 52-62
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Type of wrap if used: patches

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dermal administration of the substance solution at a dose of 2000 mg/kg using an administration volume of 0.53 - 0.72 mL.
- Concentration (if solution): 750 mg/mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed 30 min, 1 hour, 3 hours and after > 6 hours after administration and then once daily until day 14. On day 14 a complete post mortem examination was performed. The application sites were evaluated 1, 24, 48 and 72 hours after removal of the patches. Additionally, in the three male animals the application site was also evaluated on day 6 of the study.
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Interpretation of results:

GHS criteria not met

Conclusions:

According to the system of evaluation recommended for EU, the mean values of findings relevant for classification at the time-points 1, 24, 48 and 72 hours after administration were 0 for swelling, reddening and scab formation.

Executive summary:

In an acute dermal toxicity study according to OECD test guideline 402, groups of young adult Wistar rats (3/sex) were dermally exposed to Trioxabicyclooctan (100 % a.i) in 0.9% NaCl (750 mg/mL) for 24 hours at dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Females/Males > 2000 mg/kg bw

Trioxabicyclooctan is of low to moderate Toxicity based on LD50 values in males and females. Based on these results the test item does not need to be classified according to Regulation (EU) No. 1272/2008 (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Acute oral toxicity:

In an acute oral toxicity study according to OECD test guideline 401 (1987), groups of fasted, Wistar rats (5/sex) were given a single oral dose of 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane in water at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50 Females/Males > 2000 mg/kg bw

After single oral administration of 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane at 2000 mg/kg bw to male and female rats (5/sex/group) sedation and piloerection were found as clinical signs. At autopsy, no gross pathological organ changes were observed.

4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane is of LOW Toxicity based on the LD50 in female and male Wistar rats.

 

Acute dermal toxicity:

In an acute dermal toxicity study according to OECD test guideline 402, groups of young adult Wistar rats (3/sex) were dermally exposed to Trioxabicyclooctan (100 % a.i) in 0.9% NaCl (750 mg/mL) for 24 hours at dose of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Females/Males > 2000 mg/kg bw

Trioxabicyclooctan is of low to moderate Toxicity based on LD50 values in males and females.

Justification for classification or non-classification

Based on the available information 4,4-dimethyl-3,5;8-trioxabicyclo(5.1.0)octane does not need to be classified for acute oral and dermal toxicity according to Regulation (EU) No. 1272/2008.