Cuprate(4-), [2-[[[[2-hydroxy-3-sulfo-5-[[2-(sulfooxy)ethyl]sulfonyl]phenyl]azo]phenylmethyl]azo]-4-sulfobenzoato(6-)]-, sodium

Endpoint summary

Description of key information

Substance is practically not toxic

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:

June 22,1983 to July 06,1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant with international guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

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
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: male 179 g , female 187 g
- Housing: 5 rats/cage in Macrolon cages type IV
- Fasting period before study: 16 hrs before the treatment and 2 hrs after
- Diet : Rattendiät Altromin 1324 , ad libitum
- Water : ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%):55 ± 10 %
- Photoperiod : 12 hrs cycle dark/light

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

demineralized

Details on oral exposure:

Concentration 25% (w/v) in water
Dose: 5000 mg/kg bw
Apllication volume: 20 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: yes , once a week
- Frequency of clinical observations: multiple times on Day 1, twice daily thereafter
- Necropsy of survivors performed: yes

Statistics:

NA

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mL/kg bw

Based on:

test mat.

Mortality:

One female died within 3 hours after dosing. As the lung was bluish discolored, it may be that part of the test substance was aspirated during gavage.

Clinical signs:

other: Day 1: Males + females: Reduced activity, pale skin; from 2 hours onwards bluish discolored skin; bluish discolored feces on Day 1 and 2 Females: From 2 hours until end of Day 1 hunched posture; one animal showed narrowed eyelids

Gross pathology:

death female: blue liquid in GIT; lung patrially bluish discolored; skin light bluish discolored
One male: lung reddish discolored
All other rats were without abnormal findings

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance Remazol Brilliantblau is considered non toxic by oral administration.

Executive summary:

Remazol Brilliant Blue BB has been tested in male and female Wistar rats at a limit dose of 5000 mg/kg bw. The results shows a medium lethal dose (LD₅₀) of above 5000 mg/kg body weight in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

15 February 1995 to 01 March 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to recent EU and OECD test guidance in compliance with GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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
- Source: Harlan Winklemann GmbH
- Age at study initiation: Males 8 - 10 weeks, Females 12 - 14 weeks
- Weight at study initiation: Inital mean weight: Males - 224g, Females - 199g
- Fasting period before study: No data
- Housing: Conventional conditions, Makrolon Type-II cages, invidually
- Diet (e.g. ad libitum): Altronim 1324 pellets, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 55
- Air changes (per hr): 10 - 15 per hours
- Photoperiod (hrs dark / hrs light): 12 hours light/dark (artifical light from 6am to 6 pm)

Type of coverage:

occlusive

Vehicle:

castor oil

Remarks:

polyethoxylated (Cremophor EL)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back & flanks
- % coverage: 10
- Type of wrap if used: non-irritant skin plaster (Fermoflexband)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Luke warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): No data

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Males - 5
Females - 5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: Several times on the day of application then twice daily (once at weekends & bank holidays). Weighing: Directly before administration, after one week and at the end of the 14 day observation period.
- Necropsy of survivors performed: yes

Statistics:

Taking into consideration available data, the dosages are selected in such a way that graded lethality rates are obtained, which allow calculation or at least an estimate of the LD50.

Sufficient characterisation of acute dermal toxicity is reached as a rule, even if no substance-related lethality occurs at a dosage of 2000 mg/kg body weight.

The dosages are given in mg/kg body weight.

The following dosage was administered:

2000 mg/kg body weight

The calculation of the amount of test substance to be administrated was done taking into account a content of 65%.

Calculation of the Median Lethal Dose (LD50)

If calculation of the median lethal dose (LD50) is possible, it is done according to Spearman-Karher. The algorithm was adopted from SACHS, L. (Angewandte Statistik, 6.Auf1. 1984 , 178).

Should there be value pairs with a mortality of 0% and 100%, the geometric mean of the corresponding dosages is regarded as the "approximate LD50 value".

If only one dose group is used, the LD50 is estimated.

Preliminary study:

Not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died during the 14-day observation period.

Clinical signs:

other: No signs of systemic poisoning were observed after single application of 2000 mg/kg body weight. After the 21-hour exposure the skin in the area of the application site showed a blue discoloration in all rats. This coloration persisted until the 9th day

Gross pathology:

None of the animals sacrificed at the end of the 14-day observation period showed any noticeable gross pathological findings.

Other findings:

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the present investigations, the test substance is therefore to be regarded as relatively non-toxic after acute dermal exposure.

LD50 > 2000 mg/kg body weight

Executive summary:

Study conducted to recent EU test guidance 92/69/EEC part B3 and OECD test guideline 402 in compliance with GLP.

Based on the study the test substance is to be regarded as relatively non-toxic after acute dermal exposure. The test substance is not classified.

LD50 > 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Reactive Blue 220 has been tested in male and female Wistar rats at a limit dose of 5000 mg/kg bw. The results shows a medium lethal dose (LD₅₀) of above 5000 mg/kg body weight in male and female rats.

A structural analogue of Reactive Blue 220 has been tested at a limit dose of 2000 mg/kg bw for dermal toxicity and did not show any adverse effects at this dose level.

Justification for classification or non-classification

No adverse effects or mortality has been observed at limit doses of 5000 and 2000 mg/kg bw in oral or dermal toxicity studies, respectively. Hence the test substance is not classified.