2-(3-(4-amino-9,10-dihydro-3-sulpho-9,10-dioxoanthracen-4-yl)aminobenzenesulphonyl)vinyl) disodium sulphate

Endpoint summary

Description of key information

The oral and dermal LD50 is higher than 2000 mg/kg bw in rats.

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:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: NA
- Weight at study initiation: 82 - 108 g (mean: 95 g)
- Fasting period before study: 16 hours prior and 2 hours after gavage
- Housing: in groups
- Diet (e.g. ad libitum): ALTROMlN 1324 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: NA (own breeding)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

25 g/mL in deionized water

Doses:

6300, 8000, 10000, 12500 mg/kg bw

No. of animals per sex per dose:

10 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequently on day 1, twice daily thereafter
- Frequency of weighing: weekly
- Necropsy of died animals performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Probit analysis according to LINDER and WEBER

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

10 135 mg/kg bw

Based on:

test mat.

95% CL:

9 355 - 10 979

Remarks on result:

other: p = 0.05

Mortality:

6300 mg/kg: 0/10
8000 mg/kg: 1/10
10000 mg/kg: 3/10
12500 mg/kg:10/10

Deaths occurred between 30 minutes and 12 hours after gavage

Clinical signs:

other: Died animals showed the following signs prior to death: ataxia, prone position, lateral position Visible skin was bluish discolored in all treated animals After 24 hours: all surviving rats: NAD

Gross pathology:

died animals: bluish discolored inner organs

Other findings:

The dye was excreted via urine and feces.

Dose [mg/kg bw]	Mortality
6300	0/10
8000	1/10
10000	3/10
12500	10/10

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50: 10135 mg/kg bw

Executive summary:

The dye, which is present as a dark blue powder, was administered as an aqueous solution in different doses once by gavage to female SPF Wistar rats of own breeding weighing 82 - 108 g (average weight 95 g). The test was performed in female rats, as sex-related differences could not be determined in preliminary tests. Ten rats were used per dose. The rats were deprived of food 16 hours before application. 2 hours after administration of the dye, the rats were given food again. The observation period after application was 14 days. During this period, in which the animals were weighed weekly, the animals were fed the husbandry diet ALTROMIN 1324 from the company Altrogge in Lage/Lippe and tap water. Feed and water were offered ad libitum. The animals were kept in plastic cages on wood shavings. Lethally poisoned animals were dissected and macroscopically assessed.

The LD50 was determined by means of a probit analysis (method according to LINDER and WEBER); the confidence limits were calculated according to  CAVALLI-SFORZA (Dept. of Practical Mathematics of Hoechst Aktiengesellschaft).

Fatally poisoned animals died, after showing ataxia, in prone or lateral position. The hairless parts of the body were coloured blue. The dye was excreted with the faeces and urine. The body weight development of individual animals in the 10000 mg/kg bw group was delayed. The necropsy of the dead animals showed macroscopically a blue colouration of the internal organs.

Acute oral toxicity testing revealed an LD50 of 10135 mg/kg body weight. According to the usual classification based on acute toxicity (W.S. SPECTOR in the "Handbook of Toxicology"), the present dye would be considered practically non-toxic after a single oral administration.

Endpoint conclusion

Dose descriptor:

LD50

Value:

10 135 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

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Se Read Across Justification in section 13

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: males: ca 7 weeks; females: ca 8 weeks
- Weight at study initiation: mean: males: 178 g; females: 184 g
- Fasting period before study: NA
- Housing: single
- Diet: Altromin 1324 ad libitum
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): -
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25.11.1987 To: 9.12.1987

Type of coverage:

occlusive

Vehicle:

physiological saline

Remarks:

0.9% NaCl solution in the proportion of 1 g + 1 ml to form a paste

Details on dermal exposure:

Area: 30 cm²

Duration of exposure:

24 h

Doses:

2000 mg/kg BW

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight: weekly; clinical signsand mortality: frequently first day; twice daily thereafter
- Necropsy of survivors performed: yes

Statistics:

NA

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

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

Clinical signs:

other: no sytemic clinical signs were observed

Gross pathology:

No effects observed

Other findings:

Blue or red to purple discolored skin up to 6 days after test substance application

Interpretation of results:

GHS criteria not met

Conclusions:

Acute dermal LD50 male/female is greater than 2000 mg/kg.

Executive summary:

The acute dermal toxicity test in the Wistar rat was tested at a limit dose of 2000 mg/kg body weight in male and female animals. No deaths occurred after application of 2000 mg/kg bw. No signs of toxicity occurred during the entire test period. The treated skin area was blue or red to purple in colour until day 6 p.a.. The body weight development was not affected.

The necropsy of the animals killed after the end of the experiment did not reveal any macroscopically visible peculiarities.

Based on the acute dermal toxicity test in the male and female Wistar rat, the test substance has a dermal LD50 of above 2000 mg/kg body weight.

Reference 2

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:

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

Version / remarks:

84/449/EWG, B.3; OECD 402

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

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
- Age at study initiation: males: ca 7 weeks; females: ca 8 weeks
- Weight at study initiation: mean: males: 178 g; females: 184 g
- Fasting period before study: NA
- Housing: single
- Diet: Altromin 1324 ad libitum
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): -
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25.11.1987 To: 9.12.1987

Type of coverage:

occlusive

Vehicle:

physiological saline

Remarks:

0.9% NaCl solution in the proportion of 1 g + 1 ml to form a paste

Details on dermal exposure:

Area: 30 cm²

Duration of exposure:

24 h

Doses:

2000 mg/kg BW

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight: weekly; clinical signsand mortality: frequently first day; twice daily thereafter
- Necropsy of survivors performed: yes

Statistics:

NA

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

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

Clinical signs:

other: no sytemic clinical signs were observed

Gross pathology:

No effects observed

Other findings:

Blue or red to purple discolored skin up to 6 days after test substance application

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acute dermal LD50 male/female is greater than 2000 mg/kg.

Executive summary:

Die Prüfung der akuten dermalen Toxizität von Reaktiv Blau F-64 357 FW an der Wistar-Ratte ergab bei männlichen und weiblichen Tieren eine Dosis letalis media (LD50) über 2000 mg/kg Körpergewicht. Nach Applikation von 2000 mg/kg Kgw. traten

keine Todesfälle auf.

Während der gesamten Versuchszeit traten keinerlei Vergiftungssymptome auf. Die behandelte Hautfläche war bis zum 6. Tag p.a. blau bzw. rot bis lila verfärbt.

Die Sektion der nach Versuchsende getöteten Tiere ergab keine makroskopisch sichtbaren Besonderheiten.

Die Körpergewichtsentwicklung war nicht beeinträchtigt.

Aufgrund der akuten dermalen Toxizitätsprüfung an der männlichen und weiblichen Wistar-Ratte ist Reaktiv Blau F-64 357 FW nach den Einstufungskriterien der Richtlinie 83/467/EWG und der Gefahrstoffverordnung nicht kennzeichnungspflichtig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The dye, which is present as a dark blue powder, was administered as an aqueous solution in different doses once by gavage to female SPF Wistar rats of own breeding weighing 82 - 108 g (average weight 95 g). The test was performed in female rats, as sex-related differences could not be determined in preliminary tests. Ten rats were used per dose. The rats were deprived of food 16 hours before application. 2 hours after administration of the dye, the rats were given food again. The observation period after application was 14 days. During this period, in which the animals were weighed weekly, the animals were fed the husbandry diet ALTROMIN 1324 from the company Altrogge in Lage/Lippe and tap water. Feed and water were offered ad libitum. The animals were kept in plastic cages on wood shavings. Lethally poisoned animals were dissected and macroscopically assessed.

The LD50 was determined by means of a probit analysis (method according to LINDER and WEBER); the confidence limits were calculated according to  CAVALLI-SFORZA (Dept. of Practical Mathematics of Hoechst Aktiengesellschaft).

Fatally poisoned animals died, after showing ataxia, in prone or lateral position. The hairless parts of the body were coloured blue. The dye was excreted with the faeces and urine. The body weight development of individual animals in the 10000 mg/kg bw group was delayed. The necropsy of the dead animals showed macroscopically a blue colouration of the internal organs.

Acute oral toxicity testing revealed an LD50 of 10135 mg/kg body weight. According to the usual classification based on acute toxicity (W.S. SPECTOR in the "Handbook of Toxicology"), the present dye would be considered practically non-toxic after a single oral administration.

 

The acute dermal toxicity test in the Wistar rat was tested at a limit dose of 2000 mg/kg body weight in male and female animals. No deaths occurred after application of 2000 mg/kg bw. No signs of toxicity occurred during the entire test period. The treated skin area was blue or red to purple in colour until day 6 p.a.. The body weight development was not affected.

The necropsy of the animals killed after the end of the experiment did not reveal any macroscopically visible peculiarities.

Based on the acute dermal toxicity test in the male and female Wistar rat, the test substance has a dermal LD50 of above 2000 mg/kg body weight.

Justification for classification or non-classification

Substance is practically non-toxic; no clasification necessary