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Description of key information

The substance is of low toxicity with oral and dermal LD50  in the rat of above 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:
22 Sep 1998 to 13-Nov-1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Amendment to Protocol: location of the animals changed, additional "Study-Coordinator" was nominated and Tap water from Füllinsdorf and Itingen was presented to the animals
Qualifier:
according to guideline
Guideline:
other: Directive 92/69/CEE, B.1
GLP compliance:
yes (incl. QA statement)
Remarks:
Switzerland GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TVR 50
- Expiration date of the lot/batch: September 01, 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container at room temperature (approx. 20 °C) away from direct sunlight.
- Stability of the test substance in the vehicle: Stable in bi-distilled water for at least 24 h
Species:
rat
Strain:
Wistar
Remarks:
Hanlbm: WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Source : RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Füllinsdorf/ Switzerland
Number of animals per group : 3 males and 3 females
Age when treated : Males 8 weeks ; females 10 weeks.
Body weight range when treated : Males: 173.9 - 209.1 g ; Females : 168.4 - 175.9 g
Identification : By unique cage number and corresponding color-coded spots on the tail.
Acclimatization : One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study
Diet: Pelleted standard Kliba 3433, batch nos. 25/98 and 28/98 rat maintenance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation). Results of analyses for contaminants are archived at RCC.
Water: Community tap water from Füllinsdorf (September 28 to October 23, 1998) and Itingen (October 23 to 29, 1998), available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 38 - 66
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12-h artificial fluorescent light, 12-h dark cycle.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
bi-distilled water
Doses:
2000 mg/kg diluted in bi-distilled water at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
The purpose of this study was to assess the acute oral toxicity of FAT 40'571/A when administered by single oral gavage to rats, followed by an observation period of 14 days. This study should provide a rational basis for risk assessment.
The test article was placed into a glass beaker on a tared Mettler PM 460 balance and the vehicle (bi-distilled water) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment.
The preparation was made shortly before each dosing.
The animals received a single dose of the test article on a mg/kg body weight basis by oral gavage following fasting for approximately 17 to 21 h, but with free access to water. Food was provided again approximately 3 to 4 h after dosing.
Dose / kg body weight: 2000 mg
Application volume/kg body weight : 10 ml
Rationale Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test article.
OBSERVATIONS
Mortality / Viability Four times during test day 1 and once daily during days 2 to 15.
Body weights On test day 1 (pre-administration), 8 and 15.
Clinical signs Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
Statistics:
No statistical analysis was used as no deaths occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male and female: 0
Clinical signs:
other: No clinical signs were observed during the observation period in females. In males excretion of red feces caused by test article was noted on days 2 and 3 only.
Gross pathology:
No effects on organs were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose (LD50) of FAT 40'571/A after single oral administration to rats is greater than 2000 mg/kg body weight.
Executive summary:

An acute oral gavage toxicity study was carried out with FAT 40571/A according to OECD 401 guideline in Male and female Wistar rats at the dose level of 2000 mg/kg bw. There were no no clinical signs were observed during the observation period in females except in males, excretion of red feces caused by test article was noted on days 2 and 3 only. There waas no mortality and gross lesions found. There was no treatment related effects on body weight.

Based on the study results and absence of mortality, the median lethal dose (LD50) of FAT 40'571/A after single oral administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
GLP and OECD 401 guideline study

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:
22 Sep 1998 to 13 Nov 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987.
Qualifier:
according to guideline
Guideline:
other: Directive 92/69/CEE, B.3
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TVR50
- Expiration date of the lot/batch: 01-SEP-2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container at room temperature (approx. 20 °C) away from direct sunlight.
- Stability of the test substance in the vehicle: Stable in bi-distilled water for at least 24 h
Species:
rat
Strain:
Wistar
Remarks:
HanIbm (Wistar)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Füllinsdorf / Switzerland
- Age at study initiation: Males: 8 - 10 weeks; Females: 11 - 12 weeks
- Weight at study initiation: Males : 261 - 274g ; females :202 - 243 g
- Housing: Groups of five in Makrolon type-4 cages with standard softwood bedding. During treatment and observation individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet: Pelleted standard Kliba 3433, batch no. 25/98 rat maintenance diet (Kliba Mühlen AG, CH-4303 Kaiseraugst) available ad libitum. Results of analyses for contaminants are archived at RCC.
- Water: Community tap water from Füllinsdorf, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC.
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C) : 21 - 23
- Humidity (%) : 38 - 66
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12-h artificial fluorescent light, 12-h dark cycle
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
bidistilled water
Details on dermal exposure:
Approximately 24 h before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface. Only those animals without injury or irritation on the skin were used in the test.
On test day 1, the test article was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage. Application volume/kg body weight: 4.0 ml. Twenty-four h after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Statistics:
No statistical analysis was used as no deaths occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male and female: 0
Clinical signs:
other: No clinical signs of toxicological relevance were noted during the daily observations in rats of both sexes except the red coloration on the skin was produced by the test item itself, described as a dark red/brown powder. The red coloration did not preven
Gross pathology:
No effects on organs were found.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose (LD50) of FAT 40'571/A after single dermal administration to rats is greater than 2000 mg/kg body weight.
Executive summary:

An acute dermal semi-occlusive toxicity study was carried out with FAT 40571/A in Wistar rats of both sex according to OECD 402 guideline. During study period clinical signs, body weight, mortality and gross pathologicala findings were determined. No clinical signs of toxicological relevance were noted during the daily observations in rats of both sexes except the red coloration on the skin was produced by the test item itself, described as a dark red/brown powder. The red coloration did not prevent the assessment of the skin: a maculated erythema was seen in one female. However, an inflammatory response was delayed to later time period by developing crusts in most of the male and female animals after a 24- h semi-occlusive application. The crusts were transient in 2 males and persisting up to the end of the study in one male and in four females. Clinical signs such as red skin (5/5), crusts (3/4), maculate erythema (0/1) respectively.

Three female animals showed a very slight loss of body weight during the first week of observation. They recovered during the second week of observation. The body weight of the other animals was within the range commonly recorded for animals of this strain and age.

There was no mortality find during the study course. There were no gross pathological findings observed.

So, based on the study results and absence of mortality the median lethal dose (LD50) of FAT 40'571/A after single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
GLP and OECD 402 guideline study

Additional information

Acute Oral Toxicity:


An acute oral gavage toxicity study was carried out with Reactive Brown 49 according to OECD 401 guideline in Male and female Wistar rats at the dose level of 2000 mg/kg bw. No clinical signs were observed during the observation period in females except in males, excretion of red faeces caused by test article was noted on days 2 and 3 only. There was no mortality and gross lesions found. There were no treatment related effects on body weight.


Based on the study results and absence of mortality, the median lethal dose (LD50) of Reactive Brown 49 after single oral administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.


 


Acute Inhalation Toxicity:


Currently no study to assess the acute inhalation toxicity potential of Reactive Brown 49 is available. However, the vapour pressure for the substance can be considered low (1.22 x 10-23Pa) and owing to the high melting point (>400 °C). Hence the substance is considered to have low volatility. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulation only. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on vapour pressure and/or the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further the chemical is found to have n-octanol/water partition coefficient (log P) of -4.5, hence in the case of the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral and dermal toxicity studies (LD50 >2000 mg/kg bw) with no mortality or systemic toxicity, hence it does not need to be classified STOT SE. Similarly, absence of local toxicity in skin irritation as well as sensitization studies, further supports the conclusion that low toxicity is expected for the chemical via the inhalation route. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Reactive Brown 49 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.


 


Acute Dermal Toxicity:


An acute dermal semi-occlusive toxicity study was carried out with Reactive Brown 49 in Wistar rats of both sexes according to OECD 402 guideline. During study period clinical signs, body weight, mortality and gross pathological findings were determined. No clinical signs of toxicological relevance were noted during the daily observations in rats of both sexes except the red coloration on the skin was caused by the test item itself, described as a dark red/brown powder. The red coloration did not prevent the assessment of the skin: a maculated erythema was seen in one female. However, an inflammatory response was delayed to later time period by developing crusts in most of the male and female animals after a 24- h semi-occlusive application. The crusts were transient in 2 males and persisting up to the end of the study in one male and in four females.


Three female animals showed a very slight loss of body weight during the first week of observation. They recovered during the second week of observation. The body weight of the other animals was within the range commonly recorded for animals of this strain and age.


There was no mortality during the study course. There were no gross pathological findings observed at necropsy.


Based on the study results and absence of mortality the median lethal dose (LD50) of Reactive Brown 49 after a single dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight

Justification for classification or non-classification

Based on the observed LD50 of >2000 mg/kg bw in the acute oral and dermal toxicity study, the test substance Reactive Brown 49 does not considered to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.