4-(1,4-dioxa-spiro[4.5]dec-8-yl)-cyclohexanone

Endpoint summary

Description of key information

The acute oral LD50 was greater than 2000 mg/kg bw according to an OECD 401 compliant study in the rat (reference 7.2.1 -1).

The acute dermal LD50 was greater than 2000 mg/kg bw according to an OECD 402 compliant study in the rat (reference 7.2.3 -1).

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:

26 September 1996 - 27 November 1996

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

HsdCpb: WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: males: 184 - 208 g, females: 158 - 166 g
- Fasting period before study: from about 17 hours before dosing up to 4 hours after treatment
- Housing: individual
- Diet: ad libitum, except for fasting period
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23°C
- Humidity (%): 40 - 63%
- Air changes (per hr): not specified
- Photoperiod: 12 hours light / 12 hours dark

IN-LIFE DATES: From: To: 10 October 1996 - 24 October 1996

Route of administration:

oral: gavage

Vehicle:

other: aqu. methocel K4M Premium solution

Remarks:

hydroxypropyl methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle: 20 mL/kg
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

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: behaviour and general condition were monitored for at least 6 hours after administration and the daily, body weight was determined before treatment and on days 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Males: number of deaths: 0
Females: number of deaths: 0

Clinical signs:

other: 1 - 15 min post application: retention of feces, abdominal position, disturbed movements and dyspnoae were observed, which persisted up to 2 days.

Gross pathology:

no organ alterations

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 in rats was determined to be > 2000 mg/kg bw.

Executive summary:

The test item was tested for acute toxicity in rats after oral administration of 2000 mg/kg bw to 5 male and 5 female animals.

Signs of intoxication (retention of feces, abdominal position, locomotor disturbance and dyspnea) were seen 1 - 15 minutes after treatment and lasted up to day 2.

The gross pathological examination revealed no organ alterations.

The median lethal dose (LD50) after an observation period of 15 days is > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

OECD TG 401, GLP

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:

10 December 1997 - 24 December 1997

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 296 - 312 g, females: 203 - 218 g
- Fasting period before study: not specified
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 50%
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: To: 10 December 1997 - 24 December 1997

Type of coverage:

semiocclusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: males: 25 cm², females: 18 cm²
- % coverage: 10
- Type of wrap: aluminium foil, Coban elastic bandage (with drops of petrolatum), for females also micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: tissue with tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 10 mL/kg
- Concentration: 200 mg/mL

Duration of exposure:

24 h

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: twice daily, body weights were recorded on Day 1 pre-administration, 8 and 15
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Males: number of deaths: 0
Females: number of deaths: 0

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

No organ abnormalities were found in the animals at macroscopic post mortem examination.

Other findings:

Local skin effects:
Brown staining, scales and focal erythema were seen in the treated skin-areas of the animals during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 in rats was determined to be > 2000 mg/kg bw.

Executive summary:

The test item was tested for acute toxicity in rats after dermal administration of 2000 mg/kg bw to 5 male and 5 female animals.

No mortality was observed. Brown staining, scales and focal erythema were seen in the treated skin-areas of the animals during the observation period. Body weight gain was within the expected range.

No abnormalities were found in the animals at necropsy.

The dermal LD50 value in rats was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

OECD TG 402, GLP

Additional information

Acute oral toxicity study

The test item was tested for acute toxicity in rats after oral administration of 2000 mg/kg bw to 5 male and 5 female animals.

Signs of intoxication (retention of feces, abdominal position, locomotor disturbance and dyspnea) were seen 1 - 15 minutes after treatment and lasted up to day 2.

The gross pathological examination revealed no organ alterations.

The median lethal dose (LD50) after an observation period of 15 days is > 2000 mg/kg bw (reference 7.2.1 -1).

Acute dermal toxicity study

The test item was tested for acute toxicity in rats after dermal administration of 2000 mg/kg bw to 5 male and 5 female animals.

No mortality was observed. Brown staining, scales and focal erythema were seen in the treated skin-areas of the animals during the observation period. Body weight gain was within the expected range.

No abnormalities were found in the animals at necropsy.

The dermal LD50 value in rats was determined to be > 2000 mg/kg bw (reference 7.2.3 -1).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral or dermal route according to Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.