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Administrative data

Description of key information

The acute oral LD50 of FAT 36038/F in rats of both sexes observed over a period of 14 days is greater than 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:
05 October, 1993 to 17 November, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Test substance
Code number: FAT - 36'038/F
En-Nr.: 409753.32
Purity 69.4 %
Appearance: solid
Solubility: inslouble
Storage: room temperature
Expiration date: 09/98
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 185 to 245 g
- Fasting period before study: overnight
- Housing: Macrolon cages type 4, with standardized soft wood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least for 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hour/day light cycle
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled water
Details on oral exposure:
Administration of the test substance:one single oral dose, by gastric intubation (gavage)
Volume applied: 10 ml/kg bw
Doses:
2000 mg/kg bw (males and females)
No. of animals per sex per dose:
10 animals in total: 5 males and 5 females
Control animals:
no
Details on study design:
- Mortality: daily; a.m. and p.m. on working, days, a.m. on weekend days.
- Signs and symptoms: daily for 14 days
- Body weight: immediately before administration and on days 7 and 14
- Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.
- Other examinations performed: clinical signs, body weight.
Statistics:
No data
Preliminary study:
None
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred in this study.
Clinical signs:
Piloerection, hunched posture and dyspnoea were seen, being common symptoms in acute tests. Additionaly, reduced locomotor activity was observed in the females. The animals recovered within 6 days.
Body weight:
No effect on body weight gain was seen.
Gross pathology:
At necropsy, no deviations from normal morphology were found in all animals.
Other findings:
None

In-life observations:

         Administartion day              Day after administration         
  Animal N° observations  1 hrs  3 hrs  5 hrs  1  2  3  4  5  6  7  8
 2000 mg/kg, males                                
 1 -5 piloerection  +  +  ++  ++  +  +  +  +      
 1 -5 hunched posture  ++  ++  ++  +            
 1 -5 dyspnea  +  +  +  +              
  2000 mg/kg, females                                
 1 -5 piloerection  +  ++  ++  +  +  +  +  +      
 1 -5 hunched post  +  +  +  +  +  +          
 1 -5 dyspnea  +  +  +  +              
 1 -5 red. locom. act.    +  +                

+ = slight, ++ = moderate, +++ = severe

hunched post = hunched posture

red.locom.act= reduced locomotor activity

Body weight and necropsy findings:

Animal number  Body weight (g) d0   Body weight (g) d7   Body weight (g) d14   *  Gross necropsy findings
 2000 mg/kg, males               
 1  239 302  335  TS  NOA 
 2  245 317  367    TS   NOA 
 3  240 301 336    TS   NOA 
 4  241 303  345    TS   NOA 
 5  243 299  333    TS   NOA 
 Mean  242 304  343     
 SD  2.4 7.2  14.1     
 2000 mg/kg, females                     
 1  205 227  241   TS   NOA 
 2  203 240  243   TS   NOA 
 3  185 210  222   TS   NOA 
 4 200  222  229   TS   NOA 
 5  189 213  225   TS   NOA 
 Mean  196 222  232     
 SD  8.9 12.0  9.5     

* TS: terminal sacrifice

NOA: no observable abnormalities

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for FAT 36038/F was found to be greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of FAT 36038/F was assessed in albino rats according to the test guidelines OECD 401 and 92/69/EEC, B.1.

A group of ten rats (5 males and 5 females) was treated by oral gavage at dose level of 2000 mg/kg bw. Prior to dosing by gastric intubation, the animals were fasted overnight. After administration, the animals were observed daily for clinical signs and mortality. Body weight was recorded immediately before administration, on day 7 and day 14. At the end of the observation period, the animals were observed for a gross necropsy at the end of the study period.

Results:

Mortality: No deaths occurred during the test.

Signs of toxicity: Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests.Additionally, reduced locomotor activity was observed in the females. The animals recovered within 6 days.

Body weight: No effect on body weight gain was seen.

Effects in organs: At necropsy, no deviations from normal morphology were found in all animals.

Thus, upon an acute oral administration and a 14 day post-treatment observation period, the LD50 for FAT 36038/F was found to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
High quality GLP study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

A key study was performed to determine the acute oral toxicity of FAT 36038/F according to OECD Guideline 401 (Acute Oral Toxicity) and EU Method B.1 (Acute Toxicity (Oral)) by treating a group consisting 5 male and 5 female rats at dose of 2000 mg/kg bw and observed over a period of 14 days.

Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests. Additionally, reduced locomotor activity was observed in the females. The animals recovered within 6 days. They were killed and autopsied after an observation period of 14 days. No substance related gross organ changes were seen. Based on the data the acute oral LD50 of FAT 36038/F in rats of both sexes observed over a period of 14 days is greater than 2000 mg /kg bw.

In several supporting studies conducted, no mortality was seen upto 15000 mg/kg bw, hence supporting the key finding that FAT 36038 has very low toxicity on acute oral exposure.

Acute toxicity: inhalation

Currently no study for assessment of acute inhalation toxicity of Disperse Violet 057 is available. However, Disperse Violet 057 was estimated to have low vapour pressure (<0.5 KPa), so the potential for the generation of inhalable forms is low. 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. The chemical showed low toxicity potential in the available acute oral toxicity study with no mortality or systemic toxicity upto 15000 mg/kg bw, hence it does not need to be classified as STOT SE. Taking into consideration the above arguments, low toxicity potential is expected on acute exposure of Disperse Violet 057 via inhalation route. Hence, safety for human health can be estimated via route to route extrapolation and testing by the inhalation route was considered scientifically not necessary.

Acute toxicity: dermal

Currently no study to assess acute dermal toxicity of Disperse Violet 057 is available. However, the molecular weight of the chemical is 409.4 g/mol, indicating it being large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be limited. It was determined to have low water solubility of <0.8 ug/L, hence dermal uptake is likely to be low as the substance is considered as not sufficiently soluble in water to partition from the stratum corneum into the epidermis. Production and spray drying is performed in closed processes without isolation of reaction products. Isolated products consist either of liquid formulations or of dust free granules (non-dusty solid). In addition, the use of this substance will not result in aerosols, particles or droplets, so exposure to humans via the dermal route will be unlikely to occur. Risk management measures established for workers and professionals are considered sufficient to enable safe handling and use of the final products containing the formulated dye. No products for consumers are marketed, therefore exposure to consumers do not need to be taken into account for risk assessment. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >15000 mg/kg bw), with no mortality or systemic toxicity being seen, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are 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. Hence, low toxicity is expected on acute dermal exposure of Disperse Violet 057 and 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 acute oral studies, the test substance does not need to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.