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Administrative data

Description of key information

The median lethal dose (LD50) of Acid Violet 109 through oral route of administration in rats is >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:
1997
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 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
July 30, 1996
Deviations:
no
GLP compliance:
yes
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: 400047.32
- Expiration date of the lot/batch: December 1998

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 under test conditions: Stable in polyethylene glycol (PEG 400) for at least 24 hours.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, CH-4414 Füllinsdorf/ Switzerland
- Age at study initiation: Males - 8 weeks; Females - 10 weeks
- Weight at study initiation: Males - 200-214 g; Females - 183-189 g
- Fasting period before study: overnight
- Housing: Groups of five in Makrolon type-4 cages with standard softwood bedding
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
The animals received a single dose of the test article at 2000 mg/kg body weight basis by oral gavage following fasting for approximately 16.5 h, but with free access to water. Food was provided again approximately 3 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.
Doses:
2000 mg/ kg body weight
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 - Daily, Body weight - 1, 8 and 15 day
- Necropsy of survivors performed: yes
Statistics:
The LOGIT-Model could not be used as no deaths occurred.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs of toxicity were observed during the study period.
Body weight:
The body weight of the animals was within the range of physiological variability known for rats of this strain and age
Gross pathology:
No macroscopic organ findings were observed at necropsy.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The mean lethal dose (LD50) of FAT 21016/C after single oral administration in Wistar rats of both sexes is greater than 2000 mg/kg bw.
Executive summary:

Following OECD Guidelines for the Testing of Chemicals, Number 401 "Acute Oral Toxicity", Wistar rats were exposed to test substance FAT 21016/C to determine median lethal concentration (LD50). A group of five male and five female Hanlbm: WIST (SPF) rats was treated with FAT 21016/C at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (PEG 400) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths nor clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the range of physiological variability known for rats of this strain and age. No macroscopic organ findings were observed at necropsy. In conclusion, the mean lethal dose (LD50) of FAT 21016/C after single oral administration in Wistar rats of both sexes is greater than 2000 mg/kg bw.

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

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In an acute oral toxicity study (OECD 401 Guidelines) a group of five male and five female rats was treated with FAT 21016/C at 2000 mg/kg by oral gavage. No deaths occurred and no clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the range of physiological variability known for rats of this strain and age. No macroscopic organ findings were observed at necropsy. The mean lethal dose of FAT 21016/C after single oral administration to rats of both sexes, observed over a period of 14 days, considered to be >2000 mg/kg.

In another study, toxicity of FAT 20200/A in rat of both sexes observed over a period of 15 days by treating with 4 dose concentrations as 1000, 3000, 10000 and 15000 mg/kg. No mortality occured at 1000 and 3000 mg/kg bw, 1 male died at 10000 mg/kg bw and 7 animals (4 males and 3 females) died at the dose of 15000 mg/kg bw. The acute oral LD50 of FAT 20200/A in rats of both sexes observed over a period of 15 days is 13,460 (10,790 - 16,800) mg/kg.

 

Healthy Sprague-Dawley rats were exposed to test substance FAT 21016/A by oral gavage at an dose rate of 20 ml/kg. (equivalent to 5000 mg/kg. compound). No clinical symptoms were recorded and no deaths occurred during the 14 day observation period. The acute oral median lethal dose (LD50) of FAT 21016/A in rats is > 5000 mg/kg.

Acute nhalation toxicity:

Currently no study to assessthe acute inhalation toxicity potential of Acid Violet 109is available. However, the vapour pressure for the substance can be considered low (0.176 Pa) and owing to the high melting point (>350 °C). Hence the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. 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 haven-octanol/water partition coefficient (log P) of 0.144, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum, hence in the case of dust 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 toxicity studies (LD50 >2000 mg/kg bw) with no mortality or systemic toxicity being seen upto 2000 mg/kg bw, 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 Acid Violet 109 via inhalation routeand hence testing by the inhalation route was considered scientifically not necessary.

Acute dermal Toxicity:

Currently no study to assess the repeated dose dermal toxicity of Acid Violet 109 is available. However, the molecular weight of the chemical is 712.2 g/mol, indicating it being too large for dermal absorption. It has n-octanol/water partition coefficient (log P) of 0.144, indicating it being too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance will be low. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >2000 mg/kg bw), with no mortality or systemic toxicity being seen up to 2000 mg/kg bw, 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 dermal route. Further experience with similar chemical substances has demonstrated that, it is very unlikely that, toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Taking into consideration the above arguments, low toxicity potential is expected on acute dermal exposure of Acid Violet 109 and hence testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Based on the observed LD50 of >2000 mg/kg bw in the acute oral toxicity studies, the Acid Violet 109 does not need to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.