4-propylcyclohexanone

Endpoint summary

Description of key information

Acute oral toxicity: 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)

Acute dermal toxicity: 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:

1990-03-04 to 1990-05-08

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

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): 185 (169-207) g
- Fasting period before study: The rats did no receive any food from 17 hours before up to 4 hours after treatment.
- Housing: They were housed under conventional conditions in a 60 m² room with daylight and artificial fluorescent ligth (6 a.m. - 6 p.m.). The treated rats were kept separately in Makrolon cages type III (floor area: 37.5 x 21 cm = 787.5 cm², height: 15 cm) on mobile racks. During the acclimatization phase and on the day of treatment, the animals were kept on metal grids (placed above the softwood granulate) and then on conventional softwood granulate as bedding. The cages and the metal grids had been machine-cleaned before the beginning of the study. The bedding was changed three times a week.
- Diet: ad libitum, Altromin Strandard Diet Total Pathogen Free TPF N1324
- Water: ad libitum, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 - 29 °C
- Humidity (%): 33 - 46%
- Photoperiod: light phase from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 3.31 mL/kg

Doses:

1500, 2000, 2500 and 3000 mg/kg

No. of animals per sex per dose:

1500, 2500 and 3000 mg/kg: 5 females;
2000 mg/kg: 5 males and 10 females;
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:

control rats were treated with 10 mL/kg of 0.25% aqueous Methocel K 4M Premium solution)

Details on study design:

- Duration of observation period following administration: 15 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 weighted 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.

Statistics:

The body weight data were processed by means of the program TOX 511 A, developed by the Department of Technical and Scientific Data Processing of E. Merck, Darmstadt.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Only one female rat dosed with 2000 mg/kg died 6 hours after treatment. All the other rats survived the observation period.

Body weight:

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

Gross pathology:

In the female rat that died and all the rats that 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. The LD50 for males and females, after an observation period of 15 days was >2000 mg/kg.

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, 2500 and 3000 mg/kg bw to rats. The animals were observed for 15 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 2. The symptoms were: Dyspnea, locomotor disturbance, lateral and abdominal position, piloerection, salivation, pale faeces, retention of faeces, increased lacrimation, and wet anal region. Only one female rat dosed with 2000 mg/kg died 6 hours after treatment. All the other rats survived the observation period. Inhibition of body weight development and decreased body weight were observed on day 2 mainly. In the female rat that died and all the rats that 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:

no adverse effect observed

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:

1990-09-18 to 1990-01-01

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

GLP compliance:

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 (187-220) g
- Housing: They were housed under conventional conditions in a 60 m² room with daylight and artificial fluorescent light (light phase: 6 a.m. - 6 p.m.). The treated rats were kept separately in Makrolon cages type III (floor area: 37.5 x 21 cm - 787.5 cm2, height: 15 cm) on mobile racks. During the acclimatization phase and then for the first 28 hours after start of the treatment, the animals were kept on metal grids (placed above the softwood granulate) and then on conventional softwood granulate as bedding. The cages and the metal grids had been machine-cleaned before the beginning of the study. The bedding was changed three times a week.
- Diet: ad libitum, Altromin Strandard Diet Total Pathogen Free TFF N1324
- Water: tpa water; ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 31 °C
- Humidity (%): 43 to 56%
- Photoperiod: light phase from 6 a.m. - 6 p.m.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

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: 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 applied: 2.21 mL/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg

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: 15 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.

Statistics:

The body weight data were processed by means of the program TOX 511 A, developed by the Department of Technical and Scientific Data Processing of E. Merck, Darmstadt.

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.

On the day of administration general condition and motility of the rats were obviously affected by the method of administration. It was difficult to distinguish between reactions due to fixation by the rubber sleeve and symptoms possibly due to the administration of the test material. Therefore, certain reactions may have been masked.

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. The median lethal dose (LD50) for males and females, after an observation period of 15 days, was >2000 mg/kg.

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

Additional information

Acute oral toxicity:

A study according OECD TG 401 was performed to determine the acute toxicity of the test item after oral administration of 1500, 2000, 2500 and 3000 mg/kg bw to rats. The animals were observed for 15 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 2. The symptoms were: Dyspnea, locomotor disturbance, lateral and abdominal position, piloerection, salivation, pale faeces, retention of faeces, increased lacrimation, and wet anal region. Only one female rat dosed with 2000 mg/kg died 6 hours after treatment. All the other rats survived the observation period. Inhibition of body weight development and decreased body weight were observed on day 2 mainly. In the female rat that died and all the rats that 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).

Acute dermal toxcity:

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 (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 classified for acute toxicity under Regulation (EC) No 1272/2008 (CLP), as amended for the twelfth time in Regulation (EU) 2019/521.