Calcium 4-chloro-2-(5-hydroxy-3-methyl-1-(3-sulfonatophenyl)pyrazol-4-ylazo)-5-methylbenzenesulfonate

Endpoint summary

Description of key information

Acute oral toxicity:
The test item did not cause any mortality or clinical signs or necropsy findings after single oral gavage administration to male and

female rats at 2000 mg/kg bw in a OECD guideline and GLP compliant study. The LD50 (male/female rat) was greater than 2000 mg/kg body weight.
Acute dermal toxicity:
The test item did not cause any mortality or clinical signs or necropsy findings after single dermal administration to male and female

rats at 2000 mg/kg bw in a OECD guideline and GLP compliant study.
Acute inhalation toxicity:
Study was waived and classification for this endpoint is considered unwarranted. When aerosolized in respirable form, the substance is considered likely to behave like an inert dust.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

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

Remarks:

Well performed GLP and OECD guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG breeding colony
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: male 186 g - 196 g (mean 193 g), female 180 g - 195 g (mean 184 g) on day 1 (treatment)
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Altromin 1324), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: approx. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 % (w/v)
- Amount of vehicle (if gavage): 20 mL/kg body weight
- Purity: Oleum Sesami Ph. Eur. III, Mainland Pharmazeutische Fabrik GmbH, Frankfurt

Because of the large application volume the prepared test substance was divided into two portions, which were adminisetered by gavage to fasted animals at the stated dosage with a time preiod of 30 min in between.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days starting with treatment day 1
- Frequency of observations and weighing:
mortality/viability: during the first 30 minutes, hourly until 6 h after administration on day 1 and daily on days 2-15
clinical signs: during the first 30 minutes, hourly until 6 h after administration on day 1 and daily on days 2-15
body weights: on days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination

Statistics:

None

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were recorded.

Clinical signs:

other: No clinical symptoms occured in male and female animals. The faeces of both sexes was yellow coloured from day one to day three.

Gross pathology:

No macroscopic findings at scheduled necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Single application of 2000 mg test item per kg bw did not cause lethality in male and female rats during the 14 days observation period, resulting in a LD50 > 2000 mg/kg bw.

Executive summary:

One group of five male HoeWISK (SPF71) rats and one group of five female HoeWISK (SPF71) rats were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. A 10 % (w/v) solution of the test item in sesam oil was administered in two portions.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, hourly until 6 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 4 and 6 hours after administration on test day 1 (with the clinical signs) and daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No clinical symptoms occured in male and female animals and development of body weight was not impaired.

No macroscopic findings were observed for the animals at scheduled necropsy.

The LD₅₀of the test item after single oral administration to male and female rats, observed over a period of 14 days is: > 2000 mg/kg bw.

Therefore, the test item has not to be classified for acute oral toxicity or specific target organ toxicity – single exposure according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

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

Remarks:

well performed GLP and OECD guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Directive 84/449/EEC

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG breeding colony
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: male 184 g - 190 g (mean 187 g), female 192 g - 200 g (mean 195 g) on day 1 (treatment)
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 3 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Altromin 1324), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair.
Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
1.0 g test item was mixed with 2.0 mL PEG 400. The appropriate amount was spread over a 6 x 8 cm aluminium foil and applied to an area of shorn skin. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

Before treatment the back of each animal were clipped free of hair (approx. 30 cm2)

Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.

The test item was mixed with PEG 400. The appropriate amount was spread over a 6 x 8 cm aluminium foil and applied to an area of shorn skin. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.


After the 24 hour contact period the bandage was carefully removed and the treated skin was washed with lukewarm water to remove any residual test item.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2, 4 and 6 hours after dosing and subsequently once daily for fourteen days.

Statistics:

No statistical analysis was performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity. Treated skin was yellow discoloured one day after administration.

Gross pathology:

No abnormalities were noted at scheduled necropsy.

Other findings:

Yellow coloured staining was noted at the test sites one day after administration.
There were no signs of dermal irritation noted.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

Male and female rats were subjected to test acute dermal toxicity according to OECD 402 (limit test). The test item was administered at one dose level of 2000 mg/kg bw to 5 male and 5 female rats by dermal application of the test item to intact skin. During the 14 days observation period no animals died and there were no abnormalities found in necropsy. There were no signs of systemic toxicity and animals showed expected gains in body weight over the study period except one male with 4 % body weight loss.

LD50 > 2000 mg/kg bw.

Therefore, the test item has not to be classified for acute dermal toxicity or specific target organ toxicity – single exposure, according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

reliable without restriction

Additional information

Justification for selection of acute toxicity – oral endpoint
only one study available

Justification for selection of acute toxicity – dermal endpoint
only one study available

Justification for classification or non-classification

Due to the findings described above (LD50 oral in rats > 2000 mg/kg bw, LD50 dermal in rats > 2000 mg/kg bw) Pigment Yellow 191 has not to be classified as acute orally or dermally toxic according to the criteria laid down in Directive 67/548/EEC and in Regulation (EC) No 1272/2008.

It can reasonably be deduced that Pigment Yellow 191 does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified according to the criteria laid down in Directive 67/548/EEC and in Regluation (EC) No 1272/2008, because

- Pigment Yellow 191 did not cause lethal effects after administration of a single oral dose of 2.000 mg/kg bw in male and female rats

- Pigment Yellow 191 did not cause lethal effects after administration of a single dermal dose of 2.000 mg/kg bw in male and female rats

- Pigment Yellow 191 does not have to be classified as skin or eye irritating

- it is unlikely that Pigment Yellow 191 becomes systemically bioavailable after inhalation

Therefore, it is concluded that Pigment Yellow 191, when aerosolized in respirable form, is a chemically inert dust and that testing is not necessary to reach the scientific conclusion that classification is not warrantable.

Further more Pigment Yellow 191 does not have to be classified for specific target organ toxicity - single exposure according to the criteria laid down in Regulation (EC) No 1272/2008, as no specific toxic effects were observed after single exposure.