Lithium 4-[(5-amino-3-methyl-1-phenyl-1H-pyrazol-4-yl)azo]-2,5-dichlorobenzenesulphonate

Endpoint summary

Description of key information

Non harmful/toxic if swallowed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Experimental study performed on the non-salified form of the substance under registration. The difference in counter-ion does not impact the study outcomes because the ecotoxicological properties are determined by the base of the substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: s.p. Valez, Prague.
- Weight at study initiation: females 160 - 170 g; males 150 - 156 g.
- Fasting period before study: day before application.
- Housing: plastic polypropylene cages T4.
- Diet: commercial produced granulated feed mixture Altromin 1320. ca 15 g/item/day
- Water: ad libitum.
- Acclimation period: one week.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 50 ± 15 %
- Photoperiod: 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Appropriate amount of sample needed to prepare a 20 % aqueous suspension was weight, for the selected dose level of logarithmic. The sample was added to a calculated volume of water and thorough stirring with a glass rod.
- Log. dose level: 15.85 g/kg
- Sample weight: 36.00 g
- Added to the volume of water: 180 ml

Doses:

15000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: immediately after application, i.e. within 30 minutes, 3 hours after application, the following morning and afternoon and the next day at least once a day, for 14 days. Clinical diagnosis was focused on observing the appearance of skin, hair, visible mucous and nutritional status, mental activity, somatomotor activity, responses to stimuli, focusing on sensibility and reactivity, lacrimation, functional assessment of the respiratory, digestive, urogenital and circulation system.
- Necropsy of survivors performed: yes. Animals that died during the experiment are weighed and dissected; the surviving animals were weighed after 14 days, killed and dissected. Organs and muscle examined macroscopically. After exenterations internal organs were judged according to their color, size, consistency and structure. If the post mortem bladder resulted to be filled with urine, the urine biochemical tests were carried out focusing on finding proteins, blood sugar, ketone, bilirubin, urobilinoqenu and pH.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Clinical signs:

Throughout the experiment no clinical symptoms of intoxication were observed. Visual check revealed that coat the skin and visible mucous membranes appeared without abnormalities. Good nutritional status, normal mental and motor activity, reactivity and sensibility were recorded. Function circulation, respiratory, digestive and urogenital apparatus were physiologically normal.

Body weight:

Normal weight gain.

Gross pathology:

Hair, skin and visible mucous membranes: a normal appearance. The subcutaneous tissue and muscle did not show macroscopic patomorphological changes.
Nutritional status: good. Lungs pinkish color, spongy, airy without macroscopic patomorphological changes. Heart: maroon, stiffer consistency, without macroscopic patomorphological changes. Liver: dark reddish-brown color, smooth surface, stiffer consistency. Spleen: reddish-brown color, stiffer consistency, without macroscopic patomorphological changes. Kidney: maroon on a smooth surface, stiffer consistency, without macroscopic patomorphological changes.
Head, neck, stomac, gut and bladder did not show macroscopic patomorphological changes.

Interpretation of results:

other: not classified, according to the CLP Regulation (EC 1272/2008)

Conclusions:

LD50 is greater than 15000 mg/kg

Executive summary:

Method

The acute oral toxicity potential of the substance has been assayed following the testing procedures outlined into the OECD guideline 401. The substance was administered, as water solution, by gavage to 10 rats, i.e. 5 males and 5 females; a single dose of 15000 mg/kg was given. Animals were observed for the successive 14 days. Clinical diagnosis was focused on observing the appearance of skin, hair, visible mucous and nutritional status, mental activity, somatomotor activity, responses to stimuli, focusing on sensibility and reactivity, lacrimation, functional assessment of the respiratory, digestive, urogenital and circulation system. At hte end of the observation period, the surviving animals were killed and dissected.

Results

Throughout the experiment no clinical symptoms of intoxication were observed. Lungs pinkish color, spongy, airy without macroscopic patomorphological changes was observed. Heart appeared maroon, stiffer consistency, without macroscopic patomorphological changes. Liver: dark reddish-brown color, smooth surface, stiffer consistency. Spleen: reddish-brown color, stiffer consistency, without macroscopic patomorphological changes. Kidney: maroon on a smooth surface, stiffer consistency, without macroscopic patomorphological changes. Head, neck, stomac, gut and bladder did not show macroscopic patomorphological changes.

The LD50 resulted to be greater than 15000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

15 000 mg/kg bw

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:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Experimental study performed on the non-salified form of the substance under registration. The difference in counter-ion does not impact the study outcomes because the ecotoxicological properties are determined by the base of the substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: s.p. Valez, Prague.
- Weight at study initiation: 220 - 248 g.
- Housing: plastic polypropylene cages T3.
- Diet: commercial produced granulated feed mixture Altromin 1320. ca 20 g/item/day
- Water: ad libitum.
- Acclimation period: one week.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative humidity: 50 ± 15 %
- Photoperiod: 12 hrs dark / 12 hrs light

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: animals were twice depilated in back coat, involving an area of 6 x 6 cm.
- Type of wrap if used: the sample was covered with gauze, aluminum foil, technical tape around the perimeter of the hull. The dressing was covered with technical tape and clamped so that the test substance is maintained in contact with the skin so as to avoid ingestion.

TEST MATERIAL
- Application: in paste form.

Duration of exposure:

24 hours

Doses:

5.020 g/kg

No. of animals per sex per dose:

6 animals

Control animals:

yes

Remarks:

gauze soaked in acetone butyl alcohol in ratio 1: 1, then with gauze soaked in saline

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: immediately after application, i.e. within 30 minutes, 3 hours after application, the following morning and afternoon and the next day at least once a day, for 14 days. Clinical diagnosis was focused on observing the appearance of skin, hair, visible mucous and nutritional status, mental activity, somatomotor activity, responses to stimuli, focusing on sensibility and reactivity, lacrimation, functional assessment of the respiratory, digestive, urogenital and circulation system.
- Necropsy of survivors performed: yes. Animals that died during the experiment are weighed and dissected; the surviving animals were weighed after 14 days, killed and dissected. Organs and muscle examined macroscopically. After exenterations internal organs were judged according to their color, size, consistency and structure. If the post mortem bladder resulted to be filled with urine, the urine biochemical tests were carried out focusing on finding proteins, blood sugar, ketone, bilirubin, urobilinoqenu and pH.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Clinical signs:

Throughout the experiment no clinical symptoms of intoxication were observed. Visual check revealed that coat the skin and visible mucous membranes appeared without abnormalities. It was also found good nutritional status, normal mental and motor activity, reactivity and sensibility. Functionality of the circulatory, respiratory, digestive and urogenital apparatus resulted to be normal.

Body weight:

Normal weight gain.

Gross pathology:

Subcutaneous tissue and muscle, head, neck, stomac and intestine did not show macoscopic patomorfological changes.
Lung: pinkish color, spongy, airy, without macoscopic patomorfological changes.
Heart: maroon, stiffer consistency, without macoscopic patomorfological changes.
Liver: dark-brown-red color, a stiffer consistency, without macroscopic patomorphological changes.
Spleen: reddish-brown color, stiffer consistency, without macroscopic patomorphological changes.
Kidney: reddish-brown color, smooth surface, stiffer consistency, without macroscopic patomorphological changes.

Interpretation of results:

other: not classified, according to the CLP Regulation (EC 1272/2008)

Conclusions:

LD50 is greater than 5000 mg/kg

Executive summary:

Method

The acute dermal toxicity potential of the substance has been assayed following the testing procedures outlined into the OECD guideline 402. The substance was administered, as paste, by occlusive application on 6 rats; a single dose of 5000 mg/kg was given. Animals were observed for the successive 14 days. Clinical diagnosis was focused on observing the appearance of skin, hair, visible mucous and nutritional status, mental activity, somatomotor activity, responses to stimuli, focusing on sensibility and reactivity, lacrimation, functional assessment of the respiratory, digestive, urogenital and circulation system. At hte end of the observation period, the surviving animals were killed and dissected.

Results

Throughout the experiment no clinical symptoms of intoxication were observed. Visual check revealed that coat the skin and visible mucous membranes appeared without abnormalities. It was also found good nutritional status, normal mental and motor activity, reactivity and sensibility. Functionality of the circulatory, respiratory, digestive and urogenital apparatus resulted to be normal. Subcutaneous tissue and muscle, head, neck, stomac and intestine did not show macoscopic patomorfological changes.

The LD50 resulted to be greater than 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to the numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

The oral LD50 value was established to be greater than any classification limit for acute oral toxicity (oral acute toxicity category 4: 300 < ATE ≤ 2000 mg/kg bw).

The dermal LD50 value was established to exceed the highest CLP classification limit (dermal acute toxicity category 4: 1000 < ATE ≤ 2000 mg/kg bw).

In conclusion, the substance does not meet the criteria to be classified for oral and dermal acute toxicity, according to the CLP Regulation (EC 1272/2008).