REAKTIV-GELB F-68 072 FW

Endpoint summary

Description of key information

The substance has low acute oral and dermal toxicity. The LD50 is above 2000 mg/kg bw for both endpoints.

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:

01 April 1993 to 15 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral 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 species: Wistar rat
Strain: Hoe: WISKf(SPF7l)
Source: HOECHST AG, Kastengrund, SPF breeding colony
Body Weight at start of study: males x = 178 g (= 100 %)
s = ± 2 g
x min = 177 g (- 0.6 %)
x max = 181 g (+ 1.7 %)
n = 5
females x = 176 g (= 100 %)
s = ± 4 g
x min = 170 g (- 3.4 %)
x max = 181 g (+ 2.8 %)
n = 5
Age at start of study: males approx. 7 weeks
females approx. 8 weeks
Randomisation: Randomisation schemes 404/92 and 617/92
Animal maintenance: in fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate in groups of 5 animals
Room temperature: 22 ± 3 ⁰C
Relative humidity: 55 + 20 %
Lighting time: 12 hours daily
Acclimatisation: not necessary (breeding at extensive identical conditions)
Withdrawal of food: from about 16 hours before to 3 - 4 hours after treatment
Food: Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe), ad libitum
Water: tap water in plastic bottles, ad libitum
Animal identification: fur-marking with KMn04 and cage numbering

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The acute oral toxicity of Reaktiv-Gelb F-68 072 FW was tested only at a dose level of 2000 mg/kg body weight.
Five male and five female rats received the test compound as a 20% suspension, the application volume being 10 ml/kg bodyweight.
If no compound-related mortality is produced in this limit test according to the guidelines no full study has to be carried out.

Reaktiv-Gelb F-68 072 FW was suspended in the stated concentration in deionised water and distributed homogeneously by means of a magnetic stirrer.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

The prepared test substance was administered by gavage to fasted animals at the stated dosage. The observation period following treatment lasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Clinical signs:

other: The following clinical signs were observed after the application of Reaktiv-Gelb F-68 072 FW: decreased spontaneous activity, squatting posture, stilted gait, irregular respiration, bristling coat and sunken flanks. From the fourth day p.a. up to the end

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Other findings:

The faeces of all animals were mucous and discoloured orange.

Interpretation of results:

GHS criteria not met

Conclusions:

Acute oral toxicity testing of Reaktiv-Gelb F-68 072 FW in the Wistar rat yielded a median lethal dose above 2000 mg/kg b,w. in both male and female animals.

Executive summary:

The present study was conducted in compliance with OECD Guidelines for Testing of Chemicals, 401"Acute Oral Toxicity"and EEC Guideline B.1, Acute Oral Toxicity in Council Directive 84/449/EEC. This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).

 

Acute oral toxicity testing of Reaktiv-Gelb F-68 072 FW in the Wistar rat yielded a median lethal dose above 2000 mg/kg b,w. in both male and female animals.

 

After application of 2000 mg/kg b.w. no deaths occurred.

 

Clinical signs were observed after application of 2000 mg/kg b.w.t consisting of decreased spontaneous activity, squatting posture, stilted gait, irregular respiration, bristling coat and sunken flanks. Furthermore the feces of all animals were mucous and discoloured orange.

From the fourth day p.a. up to the end of the study the animals were free of symptoms.

 

Development of body weight was not impaired.

 

The animals killed at the end of the observation period showed no macroscopically visible changes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 April 1993 to 21 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 species: Wistar rat
Strain Hoe: WISKf(SPF71)
Source: HOECHST AG, Kastengrund, SPF breeding colony
Body Weight at start of study: males x = 200 g (= 100 %)
s = ± 5 g
x min = 193 g (- 3.5 %)
x max - 205 g (+ 2,5 %)
n = 5
females x = 193 g (= 100 %)
s = ± 3 g
x min = 188 g (- 2.6 %)
x max = 196 g (+ 1.6 %)
n = 5
Age at start of study: males approx. 7 weeks
females approx. 8 weeks
Randomisation: Randomisation schemes 270/89 and 297/89
Animal maintenance: in fully air-conditioned rooms in Makrolon cages (Type 3) on soft wood granulate one animal per cage
Room temperature: 22 ± 3 ⁰C
Relative humidity: 55 + 20 %
Lighting time: 12 hours daily
Acclimatisation: not necessary (breeding at identical conditions)
Food: Altromin 1324 rat diet (Altromin GmbH, Lage/Lippe), ad libitum
Water: tap water in plastic bottles, ad libitum
Animal identification: cage numbering

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

Preparation of the test substance
0.5 g Reaktiv-Gelb F-68 072 FW was moistened with 0.25 ml isotonic saline.

Test procedure
Before dermal treatment the fur was mechanically removed from the dorsal skin of the animals over an area of approximatly 30 cm2.

The appropriate amount of the test substance was moistened on an aluminium foil (6x8 cm) and distributed as uniformly as possible. Together with the foil the test substance was applied to the shaved and intact dorsal skin. The foil was held in place with an elastic plaster bandage fixed around the animal's body (Fixomull, and Elastoplast®, 8 cm in width, both manufactured by Beiersdorf).

At the end of the dermal exposure period of 24 hours the bandage was removed and the treated skin area washed with warm water in order to remove any unabsarbed remnants of the test substance.

Duration of exposure:

24 h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

The observation period after the dermal application lasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends and holidays only once. During this time the animals were weighed weekly. At the end of the observation period the animals were killed by carbon dioxide asphyxiation, dissected and examined for macroscopically visible changes.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the whole study.

Clinical signs:

irregular respiration

other: squatting posture, bristling coat, decreased spontaneous activity, hyperactivity, increased respiration rate, stilted and uncoordinated gate

Gross pathology:

The animals killed at the end of the observation period showed no macroscopically visible changes.

Other findings:

The skin of all animals was discoloured orange during the whole study.

Interpretation of results:

GHS criteria not met

Conclusions:

Acute dermal toxicity testing of Reaktiv-Gelb F-68 072 FW in the Wistar rat yielded a median lethal dose above 2000 mg/kg b,w. in both male and female animals.

Executive summary:

The present study was conducted in compliance with OECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxicity",andEEC Guideline B.3, Acute Dermal Toxicityin Council Directive 84/449/EEC.This study was conducted in compliance with the Principles of Good Laboratory Practice(GLP).

 

Acute dermal toxicity testing of Reaktiv-Gelb F-68 072 FW in the Wistar rat yielded a median lethal dose above 2000 mg/kg b,w. in both male and female animals.

 

Beside unspecific symptoms the animals showed impairments of respiration and motility as well as diarrhea. Additionally clonic convulsions, trembling, straub tail, straddling hind limbs and hypersensitivity to touch were observed in females. Four days p.a. the animals were free of clinical symptoms.

 

The skin of the animals showed encrustations and coarse scales. Additionally the skin of all animals was discoloured orange during the whole study.

 

Body weight development of the animals was not impaired.

 

The animals killed at the end of the observation period showed no macroscopically visible changes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

A study was conducted in compliance with OECD Guidelines for Testing of Chemicals, 401"Acute Oral Toxicity"and EEC Guideline B.1, Acute Oral Toxicity in Council Directive 84/449/EEC to determine the oral toxicity of the substance. Acute oral toxicity testing of Reactive Yellow F68072 in the Wistar rat yielded a median lethal dose above 2000 mg/kg bw in both male and female animals. After administration of 2000 mg/kg bw no deaths occurred. Clinical signs were observed after application of 2000 mg/kg bw consisting of decreased spontaneous activity, squatting posture, stilted gait, irregular respiration, bristling coat and sunken flanks. Furthermore the feces of all animals were mucous and discoloured orange. From the fourth day p.a. up to the end of the study the animals were free of clinical signs. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes.

A study was conducted in compliance with OECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxicity",andEEC Guideline B.3, Acute Dermal Toxicityin Council Directive 84/449/EEC to determine the dermal toxicity of the substance. Acute dermal toxicity testing of Reactive Yellow F68072 in the Wistar rat yielded a median lethal dose above 2000 mg/kg b,w. in both male and female animals. Beside unspecific symptoms the animals showed impairments of respiration and motility as well as diarrhea. Additionally clonic convulsions, trembling, straub tail, straddling hind limbs and hypersensitivity to touch were observed in females. Four days p.a. the animals were free of clinical symptoms. The skin of the animals showed encrustations and coarse scales. Additionally the skin of all animals was discoloured orange during the whole study. Body weight development of the animals was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes.

The test substance has a presumed very low vapour pressure and is a granular product, hence the potential for the generation of inhalable forms is low. In addition, production and use is done in a closed process without isolation of reaction products. The isolated product are dust free granules (non-dusty solid) which may be formulated into a liquid preparation of low volatility and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Dermal exposure is considered to be the appropriate route of exposure and has been assessed accordingly. No acute inhalation test was performed.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP and in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

 

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.