cyclohexadecanone

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50: > 2000 mg/kg bw (limit test)

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:

12 - 28 Feb 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(Commission Directive 96/54/EC)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

MINISTERIUM FÜR RAUMORDNUNG UND UMWELT DES LANDES SACHSEN-ANHALT, Germany

Test type:

acute toxic class 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
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: 233.7 ± 10.0 g (males), 193.7 ± 17.9 g (females)
- Fasting period before study: overnight, and until 3 h after administration
- Housing: individually in Makrolon Type 3 cages, granulated soft wood bedding
- Diet: ALTROMIN 1324, pelleted standard diet (ALTROMIN, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 - 23.5
- Humidity (%): 30 - 40, with a shortly falling below to 23%
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 g/10 mL
- Amount of vehicle: 1 mL/100 g bw

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g bw

CLASS METHOD
- Rationale for the selection of the starting dose: The study was performed as limit test.

Doses:

2000 mg/kg bw (step 1 and 2)

No. of animals per sex per dose:

3 males (step 1) and 3 females (step 2)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality, morbidity and general clinical condition continuously on the day of administration and subsequently once daily for 14 days. The following signs were given predominant consideration: changes in skin, fur, eyes and mucous membranes; gait and posture; respiratory, circulatory, autonomic and central nervous system; occurrence of secretions and excretions; presence of clonic or tonic movements and stereotypies or bizarre behaviour. Body weights were recorded 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations, body weight

Statistics:

Body weights and body weight gain: Calculation of group mean values and standard deviations.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the course of the study.

Clinical signs:

Not any alterations of the general state of well-being were observed during the course of the study.

Body weight:

The body weight gain was not affected by the administration of the test item, it was in the range of the historical control data in the testing facility. The body weight gain of one female animal was retarded in comparison to the historical control data in the testing facility but it can be assumed that this is not caused by the administration of the test item and seems to be accidental.

Gross pathology:

There were no macroscopic pathological findings in the animals.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute oral toxicity study in rats a LD50 value of > 2000 mg/kg bw was found.

Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423, EU Method B.1 tris and in compliance with GLP (2001). A total dose of 2000 mg/kg bw (limit test) test substance was administered to 3 male (1st step) and 3 female rats (2nd step). Animals were observed for mortality and general clinical condition on the day of administration and once daily thereafter for 14 days. Body weights were recorded on the day of administration and on days 7 and 14 thereafter. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. None of the animals died and no clinical symptoms were observed during the study. The body weight gain was not affected by the administration of the test substance. The body weight gain of one female animal was retarded in comparison to the historical control data in the testing facility but it can be assumed that this is not caused by the administration of the test substance and seems to be accidental. No pathological findings were observed at necropsy. Based on the results of this study, the oral LD50 value was determined to be > 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch Score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:

12 - 27 Feb 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

occlusive instead of semi-occlusive dressing

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

yes

Remarks:

occlusive instead of semi-occlusive dressing

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(Commission Directive 92/69/EEC)

Deviations:

yes

Remarks:

occlusive instead of semi-occlusive dressing

GLP compliance:

yes (incl. QA statement)

Remarks:

MINISTERIUM FÜR RAUMORDNUNG UND UMWELT DES LANDES SACHSEN-ANHALT, Germany

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
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: 263.8 ± 7.9 g (males), 204.8 ± 8.6 g (females)
- Fasting period before study: no
- Housing: individually in Makrolon Type 3 cages, granulated soft wood bedding
- Diet: ALTROMIN 1324, pelleted standard diet (ALTROMIN, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 - 23.5
- Humidity (%): 30 -40, with a shortly falling below to 23
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 6 cm shaved skin from the dorsal area of the trunk
- Type of wrap if used: two layers of gaze patch covered with aluminium foil, which was held in contact with the skin by occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: yes, rinsed with corn oil
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1 mL/100 g bw
- Concentration: 20% (w/v)

VEHICLE
- Amount applied: 1 mL /100 g bw

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: The animals were observed for mortality, morbidity and general clinical condition continuously on the day of administration and once daily thereafter (in the morning). The following signs were given predominant consideration: changes in skin, fur, eyes and mucous membranes; gait and posture; respiratory, circulatory, autonomic and central nervous system; occurrence of secretions and excretions; presence of clonic or tonic movements and stereotypies or bizarre behaviour. Body weights were recorded on the day of administration and on days 7 and 14 thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight; Skin of administration area was observed for erythema and/or edema one hour after patch removal and once daily thereafter.

Statistics:

Body weights and body weight gain: Calculation of group mean values and standard deviations.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the course of the study.

Clinical signs:

None of the animals showed alterations of the general state of well-being during the course of
the study.

Body weight:

The body weight gain was not affected by the administration of the test item, it was in the range of the historical control data in the testing facility. The body weight gain of one female animal stagnated in the first week but it can be assumed that this is not caused by the administration of the test item and seems to be accidental.

Gross pathology:

There were no macroscopic pathological findings in the animals.

Other findings:

None of the animals showed alterations of the skin on the administration area.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

In this acute dermal toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.

Executive summary:

The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female Wistar rats according to OECD Guideline 402, EU Method B.3 and in compliance with GLP (2001). The test substance was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then held in contact with the skin with an occlusive dressing for 24 hours. Animals were observed for mortality, general clinical condition and alterations of the administration area (erythema and/or oedema) for a 14-day period. Body weights were recorded on the day of administration and on days 7 and 14 thereafter. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. None of the animals died and no clinical signs or skin alterations on the administration area were observed. The body weight gain was not affected by the administration of the test item. The body weight gain of one female animal stagnated in the first week but it can be assumed that this is not caused by the administration of the test item and seems to be accidental. No pathological findings were observed at necropsy. Based on the results of this study, the LD50 value for acute dermal toxicity was determined to be > 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch Score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423, EU Method B.1 tris and in compliance with GLP (2001). A total dose of 2000 mg/kg bw (limit test) test substance was administered to 3 male (1st step) and 3 female rats (2nd step). Animals were observed for mortality and general clinical condition on the day of administration and once daily thereafter for 14 days. Body weights were recorded on the day of administration and on days 7 and 14 thereafter. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. None of the animals died and no clinical symptoms were observed during the study. The body weight gain was not affected by the administration of the test substance. The body weight gain of one female animal was retarded in comparison to the historical control data in the testing facility but it can be assumed that this is not caused by the administration of the test substance and seems to be accidental. No pathological findings were observed at necropsy. Based on the results of this study, the oral LD50 value was determined to be > 2000 mg/kg bw in rats.

Dermal

The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female Wistar rats according to OECD Guideline 402, EU Method B.3 and in compliance with GLP (2001). The test substance was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then held in contact with the skin with an occlusive dressing for 24 hours. Animals were observed for mortality, general clinical condition and alterations of the administration area (erythema and/or oedema) for a 14-day period. Body weights were recorded on the day of administration and on days 7 and 14 thereafter. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. None of the animals died and no clinical signs or skin alterations on the administration area were observed. The body weight gain was not affected by the administration of the test item. The body weight gain of one female animal stagnated in the first week but it can be assumed that this is not caused by the administration of the test item and seems to be accidental. No pathological findings were observed at necropsy. Based on the results of this study, the LD50 value for acute dermal toxicity was determined to be > 2000 mg/kg bw in rats.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.