Registration Dossier

Administrative data

Description of key information

No adverse effects were observed in acute toxicity studies

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:
1. November 1989 to 15. November 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: males: 183 to 191 g; females: 175 to 182 g
- Fasting period before study: 16 hours prior to 3-4 hours after dosing
- Housing: 5 per cage
- Diet: Altromin 1324 ad libitum
- Water: tap water in plastic bottles ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1. Nov To: 15. Nov 1989
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised
Details on oral exposure:
VEHICLE
- Deionised water
- Concentration in vehicle: 20%
- Amount of vehicle (if gavage) 10 mL/kg:
- Justification for choice of vehicle: highly soluble in water


Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs: twice daily - on weekends or public holidays: once daily
- Body weight: weekly
- Necropsy of survivors performed: yes

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 week-ends and public 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.
Statistics:
mean and standard deviation of body weight data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
Reddish discoloration of bedding and feces in males and females on Day 1 and 2. One females showed diarrhea on Day 1. No clinical sings from Day 3 onwards.
Body weight:
No effects on body weight development.
Gross pathology:
No macroscopic findings at necropsy.
Other findings:
None reported
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results obtained in this study, the oral median lethal dose value (LD50) of Reaktiv-Rot F-66 813 FW for the male and female rat is greater than 2000 mg/kg bw.
Executive summary:

Acute oral toxicity testing of Reaktiv-Rot F-66 813 FW in the rat yielded a median lethal dose (LD50) above 2000 mg/kg bw in both male and female rats. After administration of 2000 mg/kg bw no deaths occurred. Discolored feces and tray/bedding was observed. One female showed diarrhea. On day three of the study all symptoms were reversible.

Development of body weight was not impaired.

The animals killed at the end of the observation period showed no macroscopically visible changes. The substance is not classified for oral toxicity.

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:
02 November to 16 November 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: males: 203 to 214 g; females: 189 to 198 g
- Housing: single
- Diet: Altromin 1324 ad libitum
- Water: tap water in plastic bottles ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2. Nov To: 16. Nov 1989
Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
1 g test compound moistened with 0.8 ml 0.9% NaCl-solution was applied to a shaved skin area of approximately 30 cm2
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Clinical signs: twice daily - on weekends or public holidays: once daily
- Body weight: weekly
- Necropsy of survivors performed: yes

Prior dermal treatment the fur was removed mechanically from the dorsal skin of the animals over an area of approximately 30 cm2.

The adequate amount of Reaktiv-Rot F-66813 FW was pasted and evenly spread on sheets (size 6x8 cm) of aluminium foil. Afterwards the foil covered with test compound was applied to the shaved and intact dorsal skin and fixed with an elastic plaster bandage (Fixomull and Elastoplast, width 8 cm, Beiersdorf AG) wrapped around the animal's body.

After the end of the 24 hours dermal exposure period the bandage was removed and the treated skin area rinsed with lukewarm water to wash off any non-absorbed remnants of the test compound.

The observation period after treatment was 14 days. Clinical symptoms were recorded twice daily (morning and afternoon), on weekends and public holidays only once a day. Body weight development was determined weekly. At the end of the observation period the animals were killed by CO2 asphyxiation, dissected and examined for macroscopically visible changes.
Statistics:
mean and standard deviation of body weight data
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No Deaths occured.
Clinical signs:
No clinical signs were observed in male and female rats during the whole course of study. Only the surface of the skin was red discolored to a smaller or larger extend.
Body weight:
Body weight development was not impaired.

Gross pathology:
No macroscopically visible changes were observed in all animals killed at end of the observation period.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results obtained in this study, the dermal median lethal dose value (LD50) of Reaktiv-Rot F-66 813 FW for the male and female rat is greater than 2000 mg/kg bw.
Executive summary:

Acute dermal toxicity testing of Reaktiv-Rot F-66 813 FW in the rat yielded a dermal median lethal dose (LD50) above 2000 mg/kg bw in both male and female rats. After administration of 2000 mg/kg bw neither deaths nor clinical signs occurred. Only the surface of the skin was red discolored to a smaller or larger extend. Development of body weight was not impaired. The animals killed at the end of the observation period showed no macroscopically visible changes.

Based on the results obtained in this study, the dermal median lethal dose value (LD50) of Reaktiv-Rot F-66 813 FW for the male and female rat is greater than 2000 mg/kg bw.

Hence, Reaktiv-Rot F-66 813 FW is not classified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Testing on the above endpoints gave the following results:

 Acute toxicity: Oral.

-         LD50: >2000 mg/kg

Acute toxicity: Dermal.

-         LD50: >2000 mg/kg

Acute toxicity: Inhalation.

Not measured.

 

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.

The following information is taken into account for any hazard / risk assessment:

Oral, inhalation and dermal acute toxicity are all considered.

Value used for CSA:

LD50 (oral): 2000 mg/kg bw

LD50 (dermal): 2000 mg/kg bw

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimish 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.