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Description of key information

Based on the data of  three studies it can be concluded that the test substance FAT 41001 is not toxic by oral route. 

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
non GLP study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Code No: FAT 41001/D
Batch No: EN 94060.32
Description: solid
Contents of active ingredient: 78.8 %
Test Article Received: December 6, 1983
Species:
rat
Strain:
other: Tif:RAIf(SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland.
- Age at study initiation: 7 - 8 weeks.
- Weight at study initiation: 178 - 219 g.
- Housing: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding (Société Parisienne des sciures, Pantin).
- Diet (e.g. ad libitum): Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), ad libitum.
- Water (e.g. ad libitum): ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%):55 ± 15
- Air changes (per hr): approximately 15 air changes/h.
- Photoperiod (hrs dark / hrs light): 12 hours light/day.
Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 ml/kg bw, resp. 10
- Amount of vehicle (if gavage): 5000, 2000 mg/kg bw.

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg bw
Doses:
2000 and 5000 mg/kg bw.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: on days 1, 7, 14 and at death.
- Necropsy of survivors performed: yes.
- Other examinations performed: mortality, signs and symptoms, body weight, necropsies.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
Where feasable, the LD50 including the 95 % confidence limit were computed by the logit method (J. Berkson, J.Am. Stat. Ass. 39. 357-65, 1944)
Preliminary study:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Non toxic
Mortality:
No mortality occured at 2000 mg/kg (1 male died due to intratracheal intubation).
All animals were found dead at 5000 mg/kg bw.
Clinical signs:
Dyspnoea, exophthalmos, ruffled fur and curved body position were seen, being common symptoms in acute tests. In addition, diarrhea was noted during the first two days as well as a blue staining of the eyes and extremities.
Body weight:
No significant changes
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value in rats via oral administration of test substance FAT 41001/D was found to be greater than 2000 mg/kg bw.
Executive summary:

A study was conducted to assess acute oral toxicity of FAT 41001/D according to OECD Guideline 401 (Acute Oral Toxicity) guideline. The test substance was of 78.8% purity. The test substance was administered orally suspended in distilled water containing 0.5 % carboxymethylcellulose and 0.1 % polysorbate 80 (prepared by Pharmaceutical Division, Ciba-Geigy Ltd.). Mortality, body weight, signs and sypmtoms of toxicity were observed. Necropsy was conducted on dying animals or survivors at the end of observation period.

Symptoms:

No deaths were observed in both male and female groups at 2000 mg/kg bw. At 5000 mg/kg bw, all animals were found dead with blue stained carcass. No change in body weight. Symptoms of dyspnoea, ruffled fur, diarrhoea and hunched posture was observed. All the symptoms disappeared within 10 days of exposure period.

The LD50 value in rats via oral administration of test substance FAT 41001/D 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

Acute toxicity: via inhalation route

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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

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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 physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A key study was conducted to assess the acute oral toxicity of the test substance in Wistar rats according to OECD Guideline 401 and EU Method B.1.

Groups of 10 fasted animals (5/sex/dose) received a single oral (gavage) dose of 2000 mg/kg bw of the test substance. Parameters assessed included mortality, clinical observations, body weight and necropsy findings in all animals after a 15 d observation period. No mortality occurred and no significant macroscopic abnormalities were seen at necropsy. Under the study conditions, the oral LD50 of the test substance was found to be > 2000 mg/kg bw in rats. Couple of more studies conducted to assess the acute oral toxicity of the test substance in rats found the oral LD50 of the test substance to be > 5000 mg/kg bw. Based on the data of all the three studies it can be concluded that the test substance FAT 41001 is not toxic by oral route. Based on column 2 of the table given in REACH Annex VIII, 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 very low vapour pressure 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 inhalation route of exposure is considered to be unlikely, thus the study on acute inhalation toxicity is being waived.

Further analysis of our substance does not indicate any harm upon oral exposure and neither the chemical structure of the substance nor any toxicokinetic results raise any concern about the toxic behavior of the substance upon dermal absorption, we will not perform any test on this endpoint in in vitro or in vivo test systems.


Justification for selection of acute toxicity – oral endpoint: OECD Guideline study

Justification for selection of acute toxicity – inhalation endpoint: Based on Column 2 of the table given in REACH Annex VIII, 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 very low vapour pressure 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 inhalation route of exposure is considered to be unlikely, thus the study on acute inhalation toxicity is being waived.

Justification for selection of acute toxicity – dermal endpoint: Further analysis of our substance does not indicate any harm upon oral exposure and neither the chemical structure of the substance nor any toxicokinetic results raise any concern about the toxic behavior of the substance upon dermal absorption, we will not perform any test on this endpoint in in vitro or in vivo test systems.

Justification for classification or non-classification

Based on the above stated assessment of the acute oral toxicity the substance does not need to be classified for Acute Oral toxicity according to GLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council) as implementation of UN-GHS in the EU.