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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:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals 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:
None
Doses:
2000 mg/kg (males and females)
Volume applied: 10 ml/kg bw
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:
None
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:

A key study was conducted to determine the acute oral toxicity of FAT 36038/F in albino rats according to the test guidelines OECD 401, 92/69/EEC, B.l and the study protocol.

Ten rats (5 males and 5 females) were treated by oral gavage at dose level of 2000 mg/kg. FAT 36038/F was dissolved in distilled water. 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.

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

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 (with 95 % confidence limits calculated, where possible) was determined for FAT 36038/F:

LD50 in male rats: greater than 2000 mg/kg bw

LD50 in female rats: greater than 2000 mg/kg bw

LD50 in rats of both sexes: greater than 2000 mg/kg bw

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

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:
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:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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 male and 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, acute oral LD50 in rats was found to be greater than 5000, 10000 and 15000 mg/kg bw respectively.

The test item FAT 36038 has therefore low acute toxicity to rats by this route of administration. 

Acute toxicity: inhalation

Currently no data on acute inhalation toxicity are available. The test substance is predicted to have a very low vapour pressure and a melting point of >180 ºC following substance decomposition at about 230 °C, therefore, the potential for the generation of inhalable vapours is low. In addition, following acute oral application the test substance does exacerbate systemic toxicity effects. Taken together, due to the physical-chemical properties oral ingestion and subsequent gastro-intestinal absorption is considered to be the most relevant route of exposure. Since this route does not result in systemic toxicity, inhalation exposure is considered to be negligible for systemic toxicity. Therefore the study will be waived and the intrinsic property/toxicity potential can be extrapolated from the acute oral route administration. Exposure considerations for workers, professionals and consumers:  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 of an inhalable size, so exposure to humans via the inhalation 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.

Acute toxicity: dermal

The physicochemical and toxicological properties suggest a low potential for significant rate of absorption through the skin. Furthermore, the results of laboratory animal studies performed to assess skin irritation and skin sensitization potential displayed no acute dermal toxicity. In addition, following acute oral application the test substance was found to have low acute toxicity. Taken together, due to the physical-chemical properties oral ingestion and subsequent gastro-intestinal absorption is considered to be the most relevant route of exposure. Since this route does not result in systemic toxicity, dermal exposure is considered to be negligible for systemic toxicity. This fact is further supported by absence of systemic toxicity in skin irritation and sensitisation studies. Therefore, the study will be waived and the intrinsic property/toxicity potential can be extrapolated from the acute oral route administration. Exposure considerations for workers, professionals and consumers:  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.

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.