Reaction products of 4-amino-5-hydroxynaphthalene-2,7-disulfonic acid, coupled twice with diazotized 2-[(4-aminophenyl)sulfonyl]ethyl hydrogen sulfate, sodium salts

Endpoint summary

Description of key information

Based on the available data it can be concluded that the test substance is not toxic by oral route. 

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

Study period:

06 to 20 March 1980

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)

Principles of method if other than guideline:

Internal Guideline Hoechst AG

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: -
- Weight at study initiation: 208 to 222 g
- Fasting period before study: 16 hours before to 2 hours after dosing
- Housing: groups caging
- Diet: Altromin 1324 ad libitum
- Water: tap ad libitum
- Acclimation period: -


IN-LIFE DATES: From: 06. Mar To: 20. Mar 1980

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 %
- Amount of vehicle (if gavage): 20 mL/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality/clinical signs: al least daily; body weight: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

-

Preliminary study:

NA

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: drowsiness, piloerection, diarrhea within 1 to 3 hours after dosing. Dark bluish discoloration of skin, feces and urine within 3 to 24 hours after dosing. Discolored skin and urine were observed during the entire observation period with decreasing intensi

Gross pathology:

slight bluish discoloration of cutis and subcutis, purple discolored kidneys;

Interpretation of results:

practically nontoxic

Remarks:

Criteria used for interpretation of results: Spector, Handbook of Toxicology

Conclusions:

LD50 above 5000 mg/kg bw. No classification required.

Executive summary:

10 female rats were exposed to the test substance via oral gavage at a single concentrations of 5000 mg/kg body weight and observed for 14 days.

No mortality and adverse clinical signs were observed. No effects on body weight and in gross pathology slight bluish discoloration of cutis and subcutis, purple discolored kidneys observed. Drowsiness, piloerection, diarrhea within 1 to 3 hours after dosing. Dark bluish discoloration of skin, feces and urine within 3 to 24 hours after dosing, and discolored skin and urine were observed during the entire observation period with decreasing intensity.

Based on the observation the acute oral medial lethal dose of test substance is determined to be above 5000 mg/kg bw in female rats.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 to 26 October 1981

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)

Principles of method if other than guideline:

Internal Guideline Hoechst AG

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: -
- Weight at study initiation: 214 to 232 g
- Fasting period before study: 16 hours before to 2 hours after dosing
- Housing: group-caging (10/cage)
- Diet: Altromin 1324 ad libitum
- Water: tap ad libitum
- Acclimation period: -


IN-LIFE DATES: From: 12. Oct To: 26. Oct 1981

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 %
- Amount of vehicle (if gavage): 20 mL/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight: weekly; clinical signs: at least daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

NA

Preliminary study:

NA

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: no effects

Gross pathology:

no effects

Other findings:

bluish discoloration of skin and eyes within 1 hour after dosing; excretion of dye via feces and urine. All discolorations were reversible.

Interpretation of results:

practically nontoxic

Remarks:

Criteria used for interpretation of results: other: Spector, Handbook of Toxicology

Conclusions:

LD50 above 5000 mg/kg bw. No classification required.

Executive summary:

10 female rats were exposed to the test substance via oral gavage at a single concentrations of 5000 mg/kg body weight and observed for 14 days.

No mortality and adverse clinical signs were observed. No effects on body weight and in gross pathology were observed. Bluish discoloration of skin and eyes within 1 hour after dosing; excretion of dye via feces and urine were noted. All discolorations were reversible

Based on the observation the acute oral medial lethal dose of test substance is determined to be above 5000 mg/kg bw in female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Comparable to guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Single dose studies with oral gavage of the test item at doses up to 15000 mg/kg body weight are available. These studies showed that the test item has a very low toxicity with an oral LD50 between 14000 and 14500 mg/kg body weight. It is therefore scientifically not justified to perform an additional acute toxicity study with dermal application.

Due to the physico-chemical properties of the test item, dermal penetration is most unlikely. Due to the good water solubility, the toxicologically most relevant route of exposure is the oral one.

Inhalative exposure of workers to the test item is very unlikely, as production and spray drying is done in a closed process without isolation of reaction products. The isolated products are dust free granules (non-dusty solid) or liquid formulations, therefore, inhalative exposure of down-stream users is very unlikely, too.

Justification for selection of acute toxicity – oral endpoint
Detailed study conducted according to guideline.

Justification for selection of acute toxicity – inhalation endpoint
Data waiving: Exposure considerations
Production and spray drying is in closed process without isolation of reaction products. Isolated product is in form of dust free granules (non-dusty solid).

Justification for selection of acute toxicity – dermal endpoint
Study scientifically unjustified
Due to the physico-chemical properties of the test item, dermal penetration is most unlikely. Due to the good water solubility, the toxicologically most relevant route of exposure is the oral one. Single dose studies with oral gavage of the test substance at doses up to 15000 mg/kg body weight are available. These studies showed that the test item has a very low toxicity with an oral LD50 between 14000 and 14500 mg/kg body weight (based on test material).

Justification for classification or non-classification

Based on the above stated assessment of the acute oral toxicity the substance does not need to be classified for acute oral toxicity according to GLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council)as implementation of UN-GHS in the EU.