2-Thiophenecarboxylic acid, 5-chloro-

Endpoint summary

Description of key information

Study conducted according to OECD test guideline 423; 9 female, fasted, 10-12 weeks old Wistar strain rats were given a single oral dose of 5-Chlorthiophen-2-carbonsäure in demineralized water containing 2% Cremophor by gavage at a dose of 2000 and 300 mg/kg bw and observed for 14 days, result: LD50 ≥ 300 mg/kg bw ≤ 2000 mg/kg bw.

Study conducted according to OECD test guideline 402; one young adult male and female Wistar rats (1/sex) were dermally exposed to 5-Chlorthiophen-2-carbonsäure (100 % a.i) for 24 hours to 10 % of body surface area at a doses of 2000 mg/kg bw, result: LD50 > 2000 mg/kg bw.

 

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

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:

17 Decmber 2001

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/Winkelmann G1nbH, 5960 AD Horst, Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Fasting period before study: 16-24 h
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 161 g - 177 g
- Housing:The animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding (J. Rettenmaier & Söhne, 73494 Rosenberg, Germany).
- Diet (e.g. ad libitum): The animals received the standard diet “Provimi Kliba 3883.0.15 Maus/Ratte Haltung, Kaiseraugst Switzerland” ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups: The random list was based on evenly distributed chance numbers by a software application.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22±2
- Humidity (%): 55±5
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

with the aid of 2% Cremophor EL

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200, 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


CLASS METHOD (if applicable) acute toxic class
- Rationale for the selection of the starting dose: The starting dose level should be that which is most likely to produce mortality in some of the dosed animals. Absence or presence of compound-related mortality of the animals dosed at one step will determine the next step, i.e.:
- no further testing is needed,
- dosing ofthree additional animals, with the same dose,
- dosing of three additional animals at the next higher or the next lower dose level
The substance is tested using a stepwise procedure, each step using three animals of a single sex (normally females). The procedure is described in the flow charts of Annex 2, OECD guideline 423.

Doses:

2000 and 300 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: weekly; Observations: at least once per day
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight

Statistics:

The LD50 value was estimated according to OECD - Guideline for Testing of Chemicals No. 423 -"Acute Oral Toxicity - Acute Toxic Class Method"; adopted:
December 17, 2001.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the high dose group died within 5h to 2d.

Clinical signs:

other:

Gross pathology:

All animals treated with 2000 mg/kg bw. died during the observation period. The following changes were observed:
liver, discoloration, spotted, spleen, discoloration, pale; diminished in size, kidneys, discoloration, pale.
The necropsies performed at the end ofthe study revealed no particular findings in animals treated with 300 mg/kg bw.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to OECD guideline 423 the LD50 of 5-Chlorthiophen-2-carbonsäure is ≥ 300 mg/kg bw ≤ 2000 mg/kg bw (Category 4 ofthe Globally Harmonized Classification System).

Executive summary:

In an acute oral toxicity study according to OECD guideline 423, adopted 17 December 2001, 9 female, fasted, 10-12 weeks old Wistar strain rats were given a single oral dose of 5-Chlorthiophen-2-carbonsäure in demineralized water containing 2% Cremophor by gavage at a dose of 2000 and 300 mg/kg bw and observed for 14 days.

3 animals of the 2000 mg/kg bw group died between 5h and 2d after dosing. Clinical signs shown by the animals that suvived, i.e. the 300 mg/kg bw dose group, was only increased water intake.

No other signs were recorded.

The body weight and the body weight development of the animals were not affected by the treatment.

In animals that died during the observation period the following changes were detected:

liver, discoloration, spotted, spleen, discoloration, pale; diminished in size, kidneys, discoloration, pale.

 

No gross pathologic changes were observed in animals sacrificed at the end of the study period.

Oral LD50 ≥ 300 mg/kg bw ≤ 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

>= 300 - <= 2 000 mg/kg bw

Quality of whole database:

Guideline study, reliability high

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

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 24 February, 1987

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/Winkelmann GmbH, 33178 Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: 9-13 weeks
- Weight at study initiation: males: 237-253 g; females: 202-222 g
- Housing: The animals were caged individually in polycarbonate cages on low dust wood
granulate bedding (J. Rettenmaier & Söhne, 73494 Rosenberg, Germany)
- Historical data:
- Diet (e.g. ad libitum): The animals received the standard diet “Provimi Kliba 3883.0. 1 5 Maus/Ratte Haltung, Kaiseraugst Switzerland” ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 d
- Method of randomisation in assigning animals to test and control groups: The animals were assigned to their groups by randomization. The random list was based on evenly distributed chance numbers especially generated for the study by a software application.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±5
- Air changes (per hr):10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 30.0 cm²
- % coverage: 10%
- Type of wrap if used: wet gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a
,,Cutiplast® steril“ coated with air-tight ,,Leukoflex®“. The gauze strip was placed on the rat’s back and secured in place using ,,Peha®-Haft“ cohesive stretch tape and additionally covered with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the area was rinsed with tepid water using soap and gently patting the area dry.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 15.8 - 16.9 mg/cm² (male) 13.5 - 14.8 mg/cm² (female)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

1

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: at least once daily, weighing weekly
- Necropsy of survivors performed: yes
- Clinical signs including body weight
- Other examinations performed: clinical signs, body weight

Statistics:

An assessment ofthe LD50 was made based on the applied dose and dose-response curve, respectively.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present investigations, 5-Chlorthiophen-2-carbonsäure is to be regarded to have the following LD50 values:
LD50 rat, male : > 2000 mg/kg body weight
rat, female : > 2000 mg/kg body weight
So it is regarded as non-toxic after dermal application.

Executive summary:

In an acute dermal toxicity study according to OECD test guideline 402 (1987), one young adult male and female Wistar rats (1/sex) were dermally exposed to 5-Chlorthiophen-2-carbonsäure (100 % a.i) for 24 hours to 10 % of body surface area at a doses of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Males/Females => 2000 mg/kg bw

5-Chlorthiophen-2-carbonsäure is of low Toxicity based on the LD50 value for male and female Wistar rats. Each animal of the high dose groups (2000 mg/kg bw) survived 14 days.

 Based on the results the substance does not need to be classified according to Regulation (EU) 1272/2008 (CLP) and the Globally Harmonized System for Calssification and Labelling of Chemicals (GHS) as acute toxic via the dermal route.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Guideline study, reliability high

Additional information

In an acute oral toxicity study according to OECD guideline 423, adopted 17 December 2001, 9 female, fasted, 10-12 weeks old Wistar strain rats were given a single oral dose of 5-Chlorthiophen-2-carbonsäure in demineralized water containing 2% Cremophor by gavage at a dose of 2000 and 300 mg/kg bw and observed for 14 days.

3 animals of the 2000 mg/kg bw group died between 5h and 2d after dosing. Clinical signs shown by the animals that suvived, i.e. the 300 mg/kg bw dose group, was only increased water intake.

No other signs were recorded.

The body weight and the body weight development of the animals were not affected by the treatment.

In animals that died during the observation period the following changes were detected:

liver, discoloration, spotted, spleen, discoloration, pale; diminished in size, kidneys, discoloration, pale.

 

No gross pathologic changes were observed in animals sacrificed at the end of the study period.

Oral LD50 ≥ 300 mg/kg bw ≤ 2000 mg/kg bw

 

In an acute dermal toxicity study according to OECD test guideline 402 (1987), one young adult male and female Wistar rats (1/sex) were dermally exposed to 5-Chlorthiophen-2-carbonsäure (100 % a.i) for 24 hours to 10 % of body surface area at a doses of 2000 mg/kg bw.  Animals then were observed for 14 days.

Dermal LD50 Males/Females => 2000 mg/kg bw

5-Chlorthiophen-2-carbonsäure is of low Toxicity based on the LD50 value for male and female Wistar rats. Each animal of the high dose groups (2000 mg/kg bw) survived 14 days.

 Based on the results the substance does not need to be classified according to Regulation (EU) 1272/2008 (CLP) and the Globally Harmonized System for Calssification and Labelling of Chemicals (GHS) as acute toxic via the dermal route.

 

Justification for classification or non-classification

Based on the results the substance does not need to be classified according to Regulation (EU) 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) as acute toxic via the dermal route. The substance is classified according to the Globally Harmonised System for Classification and Labelling of Chemicals (GHS) as acutely toxic via the oral route Category 4 "harmful if swallowed".