1-chloro-4-(n-propoxy)-5-thioxanthen-10-one

Endpoint summary

Description of key information

Acute toxicity studies were performed on 1-chlor-4-(n-propoxy)-5-thioxanthen-10-one with oral and dermal routes. Based on the results of both studies, the oral and dermal LD0 are greater than 2000 mg/kg of body weight in rats or rabbits respectively.

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:

September 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

no data

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 7 weeks
- Weight at study initiation: 117-138 g
- Fasting period before study: yes
- Housing: in groups of 5 rats of the same sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 59%
- Air changes (per hr): 10-15%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

CPTX was prepared at a concentration of 50% w/v in corn oil

Details on oral exposure:

volume :10 ml/kg
Administration using a syringe and plastic catheter

Doses:

5000 mg/kg

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 for mortality, one daily for clinical signs. bodyweight recorded on Days 1, 8 and 15.
- Necropsy of survivors performed: yes (macroscopic examination)

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: Pilo-erection within 5 minutes of dosing which remainder for Day 1 in all animals but recovery completed by Day 2

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day
15.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal oral dose to rats of the test item was found to be greater than 5000 mg/kg body weight.

Executive summary:

A study was performed to assess the acute oral toxicity of CPTX to the rat. A group of ten fasted rats (5 males and 5 females) was given a single dose by gavage of the test substance, formulated in corn oil, at a dose level of 5000 mg/kg bw. All animals were killed and examined macroscopically on Day 15 (the end of the observation period). There were no deaths. Clinical signs of reaction to treatment were limited to piloerection and recovery was complete by Day 2. A slightly low bodyweight gain was recorded for one male rat on Days 8 and 15. All other rats achieved anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic exmination on Day 15. The acute lethal oral dose of CPTX was found to be greated than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 5 000 mg/kg bw

Quality of whole database:

The study is considered to be reliable with a klimisch score of 1.

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:

January - March 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

Version / remarks:

1985

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield UK
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 2.3 - 2.9 kg
- Fasting period before study:
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

corn oil

Remarks:

CPTX was prepared at a maximum practical concentration of 80% w/v in corn oil

Details on dermal exposure:

Test substance was prepared on the day of dosing.
One day prior to treatment hair was removed from the dorso-lumbar region of each rabbit with electric clippers exposing an area equivalent to approx. 10% of the total body surface.

TEST SITE
- Area of exposure: 50 mm x 50 mm
- The treated area was promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing : At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm water and blotted with absorbent paper.
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 ml/kg bw

Duration of exposure:

24h

Doses:

2000 mg/kg/ bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily for any mortality. once daily for clinical signs. Bodyweight on day 1, 8 and 15.
- Necropsy of survivors performed: yes (macroscopic examination)

Statistics:

no

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No death

Clinical signs:

other: No systemic reaction to treatment. A residual staining from the test substance was noted at all treatment sites following removal of the dressings. Transient slight to well-defined irritation (erythema with or without oedema) was observed at the majority

Gross pathology:

Macroscopic examination at study termination revealed a greasy whitish film on the surface of the spleen in three animals and in two of these animals the spleen was also considered to be slightly enlarged. Among remaining animals terminal autopsy revealed no macroscopic abnormalities with the exception of a unilateral hydronephrosis of the kidneys apparent in one female. As a low incidence of this abnormality occurs spontaneously this finding was not considered to be related to treatment. 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute lethal dermal dose to rabbits of CPTX was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute dermal toxicity of CPTX to the rabbit. A group of ten rabbits (5 males and 5 females) was given a single dermal application to the test substance, formulated in corn oil at a maximum practical concentration of 80% and administered at a dose level of 2000 mg/kg bw. All animals were killed and examined macroscopically on Day 15 (the end of the observation period). There were no deaths and no sign of systemic reaction to treatment. Transient slight to well-defined irritation (erythema with or without oedema) was observed at the majority of treatment sites following removal of the dressings and persisting in the occasional animal through to Day 7. In addition, desquamation at the treatment site , observed in five animals, was first noted in one animal on Day 5 and last seen on Day 13. There were no other dermal changes and reactions had resolved in all instances by Day 14.

A slight bodyweight loss was recorded for one female on Day 8. All other rabbits showed satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination revealed a greasy whitish film on the surface of the spleen in three animals and in two of these animals the spleen was also considered to be slightly enlarged. Among remaining animals terminal autopsy revealed no macroscopic abnormalities with the exception of a unilateral hydronephrosis of the kidneys apparent in one female. As a low incidence of this abnormality occurs spontaneously this finding was not considered to be related to treatment. 

The acute lethal dermal dose to rabbits of CPTX was found to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD0

Value:

> 2 000 mg/kg bw

Quality of whole database:

The study is considered to be reliable with a klimisch score of 1.

Additional information

Acute oral toxicity study (Huntingdon 1991)

A study was performed to assess the acute oral toxicity of CPTX to the rat. A group of ten fasted rats (5 males and 5 females) was given a single dose by gavage of the test substance, formulated in corn oil, at a dose level of 5000 mg/kg bw. All animals were killed and examined macroscopically on Day 15 (the end of the observation period). There were no deaths. Clinical signs of reaction to treatment were limited to piloerection and recovery was complete by Day 2. A slightly low bodyweight gain was recorded for one male rat on Days 8 and 15. All other rats achieved anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic exmination on Day 15. The acute lethal oral dose of CPTX was found to be greated than 5000 mg/kg bw.

 

Acute dermal toxicity study (Hundingdon 1995)

A study was performed to assess the acute dermal toxicity of CPTX to the rabbit. A group of ten rabbits (5 males and 5 females) was given a single dermal application to the test substance, formulated in corn oil at a maximum practical concentration of 80% and administered at a dose level of 2000 mg/kg bw. All animals were killed and examined macroscopically on Day 15 (the end of the observation period). There were no deaths and no sign of systemic reaction to treatment. Transient slight to well-defined irritation (erythema with or without oedema) was observed at the majority of treatment sites following removal of the dressings and persisting in the occasional animal through to Day 7. In addition, desquamation at the treatment site, observed in five animals, was first noted in one animal on Day 5 and last seen on Day 13. There were no other dermal changes and reactions had resolved in all instances by Day 14.

A slight bodyweight loss was recorded for one female on Day 8. All other rabbits showed satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination revealed a greasy whitish film on the surface of the spleen in three animals and in two of these animals the spleen was also considered to be slightly enlarged. 

The acute lethal dermal dose to rabbits of CPTX was found to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, no classification on acute toxicity is required to 1-chlor-4-(n-propoxy)-5-thioxanthen-10-one according to the Regulation EC n°1272/2008.