Reaction mass of copper complex of [(2,6-difluoroheterocycl-4-yl)amino]hydroxy{[2-hydroxy-3-sulfonato-5-(vinylsulfonyl)phenyl]diazenyl}naphthalene sulfonic acid, dialkali salt and copper complex of [(2,6-difluoroheterocycl-4-yl)amino]-hydroxy{[2-hydroxy-3-sulfonato-5-{[2-(sulfonatooxy)ethyl]sulfonyl}phenyl]diazenyl}naphthalene sulfonic acid, trialkali salt

Endpoint summary

Description of key information

The available data for test substance indicates a low potential for acute oral (LD50 >2,000 mg/kg bw) and dermal toxicity (LD50 >2,000 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

Study period:

2003-Feb-18 to 2003-Mar-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted in accordance with OECD 423 Acute oral toxicity under GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstr. 27, D-33178 Borchen
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 180 ± 6.8 g
- Housing: MacroIon cages (type 4) on soft wood granulate in groups of 3 animals per cage
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): Tap water in plastic bottles, ad libitum
- Acclimation period: At least 5 d

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

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE:
- concentration in vehicle: 20% suspension
- Amount of vehicle (if gavage): 10 mL/kg body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends
and public holidays only once. The animals were weighed weekly.
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Female: 2000 mg/kg body weight; Number of animals: 6; Number of deaths: 0

Clinical signs:

10-30 minutes after administration: stilted and uncoordinated gait, squatting posture, irregular respiration, diarrhea and feces, anal region and tray bedding were discolored (reddish).
From day 4 until end of the study no symptoms were observed.

Body weight:

Development of body weight was not impaired

Gross pathology:

No gross pathology changes

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median LD50 of Reactive Red F00-0124 for female HSD Sprague Dawley rats is >2000mg/kg body weight.

Executive summary:

In an acute oral toxicity study, a group of 6 female Hsd:Sprague Dawley Rats aged 6-10 weeks, were given a single oral dose of Reactive Red F00-0124 in deionized water at a dose of 2000 mg/kg body weight and observed for 14 days.

 

Oral LD50

Female = >2000 mg/body weight

 

Reactive Red F00-0124 is of Low toxicity based on the LD50 in female rats.

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:

2002-Nov-05 to 2002-Dec-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

GLP compliance:

yes

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: Harlan Winkelmann GmbH, Gartenstrasse 27, D-33178 Borchen
- Age at study initiation: 6-10 weeks
- Weight at study initiation: M=257g; F=207g
- Housing: transparent macrolon cages (type III) on soft wood granulate in an air-conditioned room, 1 animal per cage
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534), ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least five days

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

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 30 cm²
- Type of wrap if used: the test substance was moistened on a two-ply gauze and an aluminum foil (6 x 8 ern) and distributed as uniformly as possible. The foil was held in place with an elastic plaster bandage fixed around the animal's body.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g Reaktiv Rot F00-0124 was moistened with 0.4 mL deionized water
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and public holidays only once. During this time the animals were weighed weekly.
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg body weight; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg body weight; Number of animals: 5; Number of deaths: 0

Clinical signs:

No symptoms were observed after administration of 2000 mg/kg body weight.

Body weight:

1 female animal showed a slight loss of body weight during the first week of the study, which returned to normal until the end of the study.
In all other animals development of body weight was not impaired.

Gross pathology:

No gross patholgoy changes

Other findings:

The skin of the animals showed violett discolorations from day 2 up to day 6 of the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median LD50 of Reactive Red F00-0124 for male and female Sprague Dawley rats is > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study, groups of Hsd Sprague Dawley rats, 5/sex, were dermally exposed to Reactive Red F00-0124 in deionized water for 24 hours to 30 cm² of body surface area at a dose of 2000 mg/kg body weight. Animals then were observed for 14 days.

Dermal LD50:

Males = >2000 mg/kg body weight

Females = >2000  mg/kg body weight

Combined = >2000 mg/kg body weight 

Reactive Red F00-0124 is of low Toxicity based on LD50 is >2000 mg/kg body weight.  

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Two acute oral toxicity tests in Sprague-Dawley CD rats according to OECD guideline 423 in compliance with GLP were conducted. Animals were observed over 14 days and subjected to gross pathological examination. In one test (test 1), 6 fasted rats were given a single oral dose at a dose level of 2000 mg/kg and a further 6 animals were given a dose of 300 mg/kg. In test 2, 6 fasted rats were given a single oral dose of 2000 mg/kg. In test 1, two mortalities occurred during the study, both in the 2000 mg/kg dosage groups, which was related to an gavage error. Hence, the study was considered to be not reliable and therefore was disregarded. One occurred 2-4 hours after application and the other on day 2 of the study. Clinical signs were observed in the 2000 mg/kg. No clinical signs were observed in the 300 mg/kg group. No changes to body weight occurred for the animals killed at the end of the exposure. Macroscopic changes were observed in the two animals that died during the exposure, including to the lungs, stomach and intestines (plus additional changes in the kidneys, stomach and intestinal tract in animal Number 6 that died on day 2). No macroscopic changes were observed in the animals killed at the end of the exposure. In test 2, no deaths occurred, clinical signs were observed up to day 4 and then not observed for the remaining duration of the test. No pathological signs were recorded at the end of the test. In test 1, the test compound was classified as Class 4 of the global harmonised classification system with an LD50 of between 300 and 2000 mg/kg body weight because of a high lethality rate (2 of 3 animals in one group of the 2000 mg/kg dosage groups). However, discoloration of the lung in the dead animals indicate an application failure (aspiration during gavage). Together with the mean lethality rate in both the 2000 mg/kg groups of 33.3% and a lack of severe symptoms in the surviving animals the LD50 is considered to be above 2000 mg/kg. In test 2, the LD50 was calculated to >2000 mg/kg.

In an acute dermal toxicity study, groups of 5 Hsd:Sprague Dawley rats per sex were given a single dose of Reactive Red F00-0124 formulated in deionized water at a dose of 2000 mg/kg body weight. Animals were then observed for 14 days. No mortality of clinical signs were observed after administration; violet discoloration was visible from day 2 to day 6. The dermal LD50 is >2000 mg/kg body weight, therefore Reactive Red F00-0124 is of low dermal toxicity.

Justification for selection of acute toxicity – oral endpoint
An acute oral toxicity study in rats was performed according to OECD guidelines 423 and following GLP.

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study

Justification for classification or non-classification

No adverse effects relevant for classification and labelling have been concluded based on acute oral and dermal toxicity studies, performed according to OECD 423 and 402.