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Description of key information

The substance is practically non-toxic with an oral and dermal LD50 > 2000 mg/kg bw

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:
20 October 1998 to 03 November 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to EU & OECD test guidance in compliance with GLP.
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:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Sprague Dawley rat
Strain: HSD: Sprague Dawley SO
Origin: HARLAN WINKELMANN Gartenstr. 27, 33178 Borchen SPF breeding colony
Body weight at start of study: male animals: mean = 196g (=100%)
s = ±5.8g
min = 190g (-3.1%)
max = 205g (+4.6%)
n = 5
female animals: mean = 180g (=100%)
s = ±6.2g
min = 170g (-5.6%)
max = 187g (+3.9%)
n = 5
Age at the start of the study: 6 – 10 weeks
Randomization: Randomization schemes 93,0603 and 93,0702
Animal maintenance: in fully air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5 animals
Room temperature: 22 ± 3⁰C
Relative humidity: 50 + 20%
Lighting time: 12 hours daily
Acclimatization: at least seven days
Food: ssniff* R/M-H (V 1534), ad libitum
Withdrawal of food: from about 16 hours before to 3 - 4 hours after treatment
Water: tap water in plastic bottles, ad libitum
Animal identification: fur marking with KMnOj and cage numbering
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionised
Details on oral exposure:
Test groups
The animals received the compound as a 20 % solution in deionised water, the administration volume being 10 ml/kg body weight.

If no compound-related mortality is produced in this limit test according to the guidelines no full study has to be carried out

Preparation of the test compound
Reaktiv-Orange DYPR 1410 was dissolved in the stated concentration in deionised water and distributed homogeneously by means of a magnetic stirrer.

The stability and the homogeneity of the test substance in the vehicle was determined by analytical methods.
Doses:
The acute oral toxicity of Reaktiv-Orange DYPR 1410 was tested only at a dose level of 2000 mg/kg body weight.
No. of animals per sex per dose:
Male 5
Female 5
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 fasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends 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:
Not reported.
Preliminary study:
Not applicable
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: No symptoms were observed after administration of 2000 mg/kg body weight.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Other findings:
Only reddish discolored feces were observed in some male and female animals after the administration of Reaktiv-Orange DYPR 1410, At day two of the study all clinical signs were reversible.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of Reaktiv-Orange DYPR 1410 for the male and female rat is greater than 2000 mg/kg body weight.
Executive summary:

A study to assess the acute toxic effects of the test item was conducted in compliance with EEC-Guideline B,1. "Acute Oral Toxicity" of the Directive 92/69/EEC and OECD Guidelines for Testing of Chemicals, 401 “Acute Oral Toxicity”. This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).

No lethality occurred after administration of 2000 mg/kg body weight. Only reddish discoloured faeces were observed in same male and female animals. At day two of the study all clinical signs were reversible. With exception of one female, which suffered a loss of weight between day 8 and day 15, the body weight of all surviving animals increased during the observation period. The animals killed at the end of the observation period showed no macroscopically visible changes.

Acute oral toxicity testing of Reaktiv-Orange DYPR 1410 in the rat yielded a median lethal dose (LD50) above 2000 mg/kg body weight in both male and female animals. The substance is not classified as acutely harmful by oral exposure.

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:
18 November 1998 to 02 December 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to EU & 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:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species: Sprague Dawley rat
Strain: HSD: Sprague Dawley SD
Origin: HARLAN WINKELMANN Gartenstr. 27, 33178 Borchen SPF breeding colony
Body weight at start of study
male animals: mean = 231g (=100%)
s = ±2.7g
min = 228g (-1.3%)
max = 234g (+1.3%)
n 5
female animals: mean = 202g (=100%)
s = ±4.7g
min = 198g (-2.0%)
max = 210g (+4.0%)
n 5
Age at the start of the study: 6-10 weeks
Randomization: Randomization schemes 98.0611 and 98.0703 as per the laboratory protocol.
Animal maintenance: in fully air-conditioned rooms in macrolon cages (type 3) on soft wood granulate, one animal per cage
Room temperature: 22 ± 3°C
Relative humidity: 50 ± 20 %
Lighting time: 12 hours daily
Acclimatization: at least seven days
Food: ssnifT R/M-H (V 1534), ad libitum
Water: tap water in plastic bottles, ad libitum
Animal identification: cage numbering
Type of coverage:
occlusive
Vehicle:
other: deionized water
Details on dermal exposure:
To check the suitability of the vehicle 0.5 g Reaktiv-Orange DYPR 1410 was moistened with 0.3 ml deionized water.

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

The appropriate amount of the test substance was moistened on an aluminium foil (6 x 8 cm) and distributed as uniformly as possible. Together with the foil the test substance was administered 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 Aktiengesellschaft).
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 unabsorbed remnants of the test substance.
Duration of exposure:
24 h
Doses:
The acute dermal toxicity of Reaktiv-Orange DYPR 1410 was tested only at a dose level of 2000 mg/kg body weight.
If no compound-related mortality is produced in this limit test according to the guidelines no full study has to be carried out.
No. of animals per sex per dose:
10 - 5 male, 5 female.
Control animals:
no
Details on study design:
The observation period after the dermal administration lasted for 14 days. Symptoms were recorded twice every day (in the morning and in the afternoon), on weekends 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:
No 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 occurred during the whole study
Clinical signs:
other: No symptoms were observed after administration of 2000 mg/kg body weight.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Other findings:
Two days after administration up to the end of the study the animals showed orange discoloured skin.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in this study the median lethal dose value (LD50) of Reaktiv-Orange DYPR 1410 for the male and female rat is greater than 2000 mg/kg body weight.
Executive summary:

Testing for acute dermal toxicity provides information on health risks resulting from acute dermal exposure and serves as a basis for classification and labelling. It permits the selection of optimum dose levels for repeated dermal toxicity testing and gives the first indications on the percutaneous resorptive properties of a substance. The rat has proved to be a suitable species for acute dermal toxicity testing with many different substances.

 

The study was conducted in compliance with EEC-Guideline B.3. "Acute Dermal Toxicity" of the Directive 92/69/EEC andOECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxicity". This study was conducted in compliance with the Principles of Good Laboratory Practice.

 

Acute dermal toxicity testing of Reaktiv-Orange DYPR 1410 in the rat yielded a median lethal dose above 2000 mg/kg body weight in both male and female animals. After administration of 2000 mg/kg b.w. neither deaths nor symptoms occurred.

 

Two days after administration up to the end of the study the animals showed orange discolored skin.

 

Development of body weight was not impaired, with exception of one female animal which showed a decrease from day 1 to day 6.

 

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 to assess the acute toxic effects of the test item was conducted in compliance with EEC-Guideline B,1. "Acute Oral Toxicity" of the Directive 92/69/EEC and OECD Guidelines for Testing of Chemicals, 401 “Acute Oral Toxicity”. This study was conducted in compliance with the Principles of Good Laboratory Practice (GLP).

No lethality occurred after administration of 2000 mg/kg body weight. Only reddish discoloured faeces were observed in same male and female animals. At day two of the study all clinical signs were reversible. With exception of one female, which suffered a loss of weight between day 8 and day 15, the body weight of all surviving animals increased during the observation period. The animals killed at the end of the observation period showed no macroscopically visible changes.

Acute oral toxicity testing of Reaktiv-Orange DYPR 1410 in the rat yielded a median lethal dose (LD50) above 2000 mg/kg body weight in both male and female animals. The substance is not classified as acutely harmful by oral exposure.

A study was conducted to assess the acute toxic effects of the test item in compliance with EEC-Guideline B.3. "Acute Dermal Toxicity" of the Directive 92/69/EEC and OECD Guidelines for Testing of Chemicals, 402 "Acute Dermal Toxicity". This study was conducted in compliance with the Principles of Good Laboratory Practice.

After administration of 2000 mg/kg body weight neither deaths nor symptoms occurred. Two days after administration up to the end of the study the animals showed orange discoloured skin. Development of body weight was not impaired, with exception of one female animal which showed a decrease from day 1 to day 6. The animals killed at the end of the observation period showed no macroscopically visible changes.

Acute dermal toxicity testing of Reaktiv-Orange DYPR 1410 in the rat yielded a median lethal dose (LD50) above 2000 mg/kg body weight in both male and female animals. The substance is not classified as acutely harmful by dermal exposure.

Acute toxicity: Inhalation.

Not measured.

 

The test substance has a presumed very low vapour pressure and is a granular or well dedusted 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 or well dedusted powder (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 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.