4-pentylcyclohexanone

Endpoint summary

Description of key information

oral: A study according to OECD TG 401 was performed to determine the acute toxicity of the test item after oral administration to rats. The median lethal dose (LD50 ) for males and females, after an observation period of 15 days, was > 2000 mg/kg bw (reference 7.2.1 -1).

dermal:

A study according to OECD TG 402 was performed to determine the acute toxicity in rats after epicutaneous administration. The median lethal dose (LD50) for males and females, after an observation period of 15 days, was > 2000 mg/kg (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:

March 14 until April 24, 1990

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:

adopted February 24, 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Chbb: THOM

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach
- Age at study initiation: about 5 to 9 weeks
- Weight at study initiation: mean 186 (172 - 205) g
- Fasting period before study: The rats did not receive any food from 17 hours before up to 4 hours after treatment.
- Housing: separately in Makrolon cages type III
- Diet: ad libitum, Altromin Strandard Diet Total Pathogen Free TFF N1324
- Water: ad libitum, tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25-27
- Humidity (%): 36-46
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.79 mL/kg

Doses:

1500, 2000, 2500 mg/kg bw

No. of animals per sex per dose:

5
A further 10 animals (5 males and 5 females) from another study (T 13319) served as controls for body weight development.

Control animals:

yes

Remarks:

The control rats were treated with 10 mL/kg of a common carrier medium (0.25 % aqueous Methoce1 K 4M Premium solution).

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behavior and general condition of all rats were monitored for 4-6 hours after administration and then checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study.
- Necropsy of survivors performed: yes
All the rats which died and which were sacrificed at the end of the study by CO2-asphyxia were subjected to gross pathological investigation.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two female rats, dosed with 2000 mg/kg, died 6 hours or 2 days after treatment, respectively. Only one rat dosed with 2500 mg/kg died on day 2. All the other rats survived the observation period.

Clinical signs:

Intoxication symptoms started directly after treatment and lasted up to day 3. The symptoms were: Dyspnea, locomotor disturbance, abdominal position, piloerection, pale faeces, retention of faeces, increased lacrimation, and wet anal region.

Body weight:

Inhibition of body weight development and decreased body weight were observed on day 2 mainly.

Gross pathology:

One rat that died showed inspissation of faeces in the cecum. The second rat showed focal hemorrhage in the left adrenal. The third one was without special findings.
In all rats which were sacrificed at the end of the observation period no organ alterations were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw after oral treatment in rats.

Executive summary:

A study according OECD TG 401 was performed to determine the acute toxicity of the test item after oral administration of 1500, 2000 and 2500 mg/kg bw to rats (5 animals/sex/dose). The animals were observed for 14 days. Behavior and general condition of all rats were monitored for 4-6 hours after administration and then checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study. Necropsy was performed. Intoxication symptoms started directly after treatment and lasted up to day 3. The symptoms were: Dyspnea, locomotor disturbance, abdominal position, piloerection, pale faeces, and retention of faeces, increased lacrimation, and wet anal region. Two female rats, dosed with 2000 mg/kg bw, died 6 hours or 2 days after treatment, respectively. Only one rat dosed with 2500 mg/kg bw died on day 2. All the other rats survived the observation period. Inhibition of body weight development and decreased body weight were observed on day 2 mainly. One rat that died showed inspissation of faeces in the cecum. The second rat showed focal hemorrhage in the left adrenal. The third one was without special findings. In all rats which were sacrificed at the end of the observation period no organ alterations were seen. The median lethal dose (LD50 ) for males and females, after an observation period of 15 days, was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

OECD TG 401

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:

September 18 until October 02, 1990

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:

adopted February 24, 1987

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Chbb: THOM

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach
- Age at study initiation: about 7 to 9 weeks
- Weight at study initiation: mean 201 (188 - 220) g
- Housing: kept separately in Makrolon cages type III
- Diet: ad libitum, Altromin Strandard Diet Total Pathogen Free TFF N1324
- Water: ad libitum, tap water
- Acclimation period: 7days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-31
- Humidity (%): 43-56
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

.

Details on dermal exposure:

TEST SITE
- Area of exposure: The backs and abdomens of the rats were shaved with an electric hair clipper approximately one hour before treatment.
- Type of wrap if used: The test material was applied to the shaven, unscarified skin in an area of 6 x 6 cm and covered with tin foil which was kept in place and sealed by a rubber sleeve.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h
After exposure rubber sleeve and tin foil were removed and any remaining test material was wiped off carefully.

TEST MATERIAL
- Amount(s) applied: 2.23 mL/kg
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Remarks:

The control rats were treated with 20 mL/kg 0.25 % aqueous Methocel K 4M Premium solution.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Behavior and general condition of all rats were checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study.
- Necropsy of survivors performed: yes
All the rats were sacrificed at the end of the study by CO2-asphyxia and subjected to gross pathological investigation.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All the rats survived the observation period.

Clinical signs:

After removal of the rubber sleeve the rats showed neither intoxication nor local symptoms.

Body weight:

Body weight development of treated and control rats was normal.

Gross pathology:

In the rats which were all sacrificed at the end of the observation period no organ alterations were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, it is concluded that the test material has no acute toxic potential and that the LD50 value is higher than 2000 mg/kg bw after dermal application to rats.

Executive summary:

A study according OECD TG 402 was performed to determine the acute toxicity in rats after epicutaneous administration. The test material was applied undiluted to shaved backs and abdomens of the rats for 24 hours under occlusive conditions. Behavior and general condition of all rats were checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study. All the rats were sacrificed at the end of the study by CO2-asphyxia and subjected to gross pathological investigation. In this limit test with 2000 mg/kg bw no animal died and no gross pathology changes were detected. The median lethal dose (LD50) for males and females, after an observation period of 15 days, was > 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

Additional information

oral

A study according to OECD TG 401 was performed to determine the acute toxicity of the test item after oral administration of 1500, 2000 and 2500 mg/kg bw to rats (5 animals/sex/dose). The animals were observed for 14 days. Behavior and general condition of all rats were monitored for 4-6 hours after administration and then checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study. Necropsy was performed. Intoxication symptoms started directly after treatment and lasted up to day 3. The symptoms were: Dyspnea, locomotor disturbance, abdominal position, piloerection, pale faeces, and retention of faeces, increased lacrimation, and wet anal region. Two female rats, dosed with 2000 mg/kg bw, died 6 hours or 2 days after treatment, respectively. Only one rat dosed with 2500 mg/kg bw died on day 2. All the other rats survived the observation period. Inhibition of body weight development and decreased body weight were observed on day 2 mainly. One rat that died showed inspissation of faeces in the cecum. The second rat showed focal hemorrhage in the left adrenal. The third one was without special findings. In all rats which were sacrificed at the end of the observation period no organ alterations were seen. The median lethal dose (LD50 ) for males and females, after an observation period of 15 days, was > 2000 mg/kg bw (reference 7.2.1 -1).

dermal:

A study according to OECD TG 402 was performed to determine the acute toxicity in rats after epicutaneous administration. The test material was applied undiluted to shaved backs and abdomens of the rats for 24 hours under occlusive conditions. Behavior and general condition of all rats were checked daily. All rats were weighed before treatment, as well as on days 2, 4, 6, 8, 11, 13 and 15 of the study. All the rats were sacrificed at the end of the study by CO2-asphyxia and subjected to gross pathological investigation. In this limit test with 2000 mg/kg bw no animal died and no gross pathology changes were detected. The median lethal dose (LD50) for males and females, after an observation period of 15 days, was > 2000 mg/kg bw (reference 7.2.3-1).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for acute oral and dermal toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) No 2019/521.