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Description of key information

The acute oral LD50 of FAT 20042 in rats of both sexes observed over a period of 14 days is >2000 mg/kg bw, whereas the acute inhalation LC50 for FAT 20042 is >1353 mg/m³ air.

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:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
None
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Guideline followed
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Test article: FAT 20042/D
- Additional specification: Neolan Rosa BE ZP feucht
- Batch No.: 276
- Purity/Contents: ca. 50 %
- Physical properties: solid; black-red humid lumps
- Storage conditions: room temperature
- Validity: October, 1998
- Safety precautions: gloves and face masks
- Test material received: November 19, 1993
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: 175 to 204 g
- Housing: Macrolon cages type 4
- Diet: ad libitum ((NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland)
- Water: ad libitum
- Acclimation period: at least 5 days
- Fasting- overnight before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
None
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
None
Statistics:
None
Preliminary study:
None
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 dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 to 4 days.
Body weight:
Body weight and body weight gain were not affected.
Gross pathology:
At necropsy, no deviations from normal morphology were found in all animals.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of compound FAT 20042/D in rats is >2000 mg/kg bw.
Executive summary:

FAT 20042/D was investigated for acute oral toxicity in a study conducted according to OECD Guideline 401. In this study, group of rats (5 males and 5 females) were administered the test substance at 2000 mg/kg bw and observations for mortality, clinical signs, body weights were done for 14 days post administration. No mortalities occurred in this study. Piloerection , hunched posture, and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 to 4 days. Body weight and body weight gain were not affected. At necropsy, no deviations from normal morphology were found in all animals. Based on the findings, the acute oral median lethal dose (LD50) of compound FAT 20042/D in rats was found to be >2000 mg/kg bw in both sexes.

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
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
None
Principles of method if other than guideline:
Nose only exposure of rats to aerosols generated by injecting two different amounts of the solid test material with the help of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was discharged into the exposure chamber at a rate of 20 l/min. Exposed animals were then observed for mortality, clinical signs and body weight changes over 14 days observation period. Using the Probit method on the mortality observed, LC50 for the substance was estimated.
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
None
Species:
rat
Strain:
other: Tif : RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In house bred
- Housing: Separately, in Macrolon cages, type 4
- Diet: rat food (NAFAG, Gossau SG), ad libitum
- Water: ad libitum
- Acclimatization: minimum of 4 days


ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Photoperiod: 10 hours light cycle day

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
not specified
Mass median aerodynamic diameter (MMAD):
> 7 µm
Remark on MMAD/GSD:
Particle size distribution analysis of the chamber airborne particles showed that approximately 40 % were smaller than 7 µm in diameter.
Details on inhalation exposure:
For inhalation the rats were kept in separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the aerosol. During the exposure period the following parameters were controlled once at half time of the study inside the inhalation cylinder: temperature (with a Therm 2104 contact thermometer, Ahlborn Messund Regeltechnik, 815 Holzkirchen, Germany), relative humidity (with a VASALA Humidity Indicator HMI 11, Kelag AG, 8057 Zurich, Switzerland) and oxygen content (with a DRAEGER E 15 stationary control system, Draegerwerk AG, Lübeck, Germany).
After a 4 hour inhalation the rats were returned to their cages. Physical condition and incidence of death were monitored throughout an observation period of 14 days.

Preparation of aerosol
The aerosol was generated by injecting two different amounts of the solid test material with the help of a Grafix Exaktomat Injector (Cerutti AG, Bern, Switzerland) into an air stream which was discharged into the exposure chamber at a rate of 20 L/min. The control animals were exposed to filtered air under the same conditions as the animals exposed to the test substance.

The concentration and the particle size distribution of the aerosol in the vicinity of the animals were monitored at regular intervals throughout the aerosol exposure. The concentration was determined 5 times gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured twice with a 4 stage Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
0, 877 and 1353 mg/m3
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (mortality and clinical signs): daily
- Frequency of observations (body weight): Day 1 (before exposure), 7 and 14
- Necropsy of survivors performed: yes
Statistics:
None
Preliminary study:
No data
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 300 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality observed.
Clinical signs:
other: Dyspnoea, exophthalmos, ruffled fur and curved body position were observed at both doses. The animals exposed to the test material recovered within 4 days. The control rats failed to show any symptoms during the exposure and observation period.
Body weight:
No significant change was seen with body weight and body weight gains of the exposed animals.
Gross pathology:
Partially congested organs were observed.
Other findings:
None

Environmental conditions recorded in the exposure chamber:

- Temperature: 23 - 24 °C

- Relative humidity: 48 - 58 %

- Oxygen content volume : 20 %

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 for FAT 20042/B was estimated to be >1353 mg/m3.
Executive summary:

The acute inhalation toxicity of FAT 20042/B was investigated in a study conducted according to the method of Sachsse et al. (1973, 1976). In this study, groups of young adult rats (each consisting of 10 males and 10 females) were exposed to test concentrations of 0, 877 and 1353 mg/m3. 4 hour inhalation exposure was given to the rats through tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only got exposed. Mortality, clinical signs and body weight changes were monitored throughout an observation period of 14 days and the surviving animals were subjected to the gross necropsy after the completion of observation period. Particle size distribution analysis of the chamber airborne particles showed that approximately 40 % were smaller than 7 µm in diameter. No mortality observed throughout the study. Dyspnoea, exophthalmos, ruffled fur and curved body position were observed at both doses. The animals exposed to the test material recovered within 4 days. The control rats failed to show any symptoms during the exposure and observation period. No significant change was seen with body weight and body weight gains of the exposed animals. Partially congested organs were observed at gross necropsy. based on the findings of the study, the LC50 for FAT 20042/B was estimated to be >1353 mg/m3.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 300 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

Acid Red 195 had been evaluated in three different acute oral toxicity studies. Outcome from all three studies indicate that Acid Red 195 on acute oral exposure has low toxicity potential.

In a key study (1994), FAT 20042/D was investigated for acute oral toxicity according to OECD Guideline 401. In this study, group of rats (5 males and 5 females) were administered the test substance at 2000 mg/kg bw and observations for mortality, clinical signs, body weights were done for 14 days post administration. No mortalities occurred in this study. Piloerection , hunched posture, and dyspnea were seen, being common symptoms in acute tests. The animals recovered within 3 to 4 days. Body weight and body weight gain were not affected. At necropsy, no deviations from normal morphology were found in all animals. Based on the findings, the acute oral median lethal dose (LD50) of compound FAT 20042/D in rats was found to be >2000 mg/kg bw in both sexes.

In a supporting study (1978) conducted to evaluate the acute oral toxicity potential, FAT 20042/B was administered to groups of rats (each consisting of 5 males and 5 females) by oral gavage, at doses of 5000, 6000 and 7000 mg/kg bw. The treated animals were observed for mortality, clinical signs and body weight changes over 14 days post administration of the test substance and subjected to gross necropsy after the completion of observation period. No mortality was observed at any of the administered doses. Dyspnoea, exophthalmos, ruffled fur, diarrhoea and curved body position being the common clinical signs in acute tests were observed. The animals recovered within 9 to 12 days. Body weight and body weight gains were not affected. No substance related gross organ changes were seen. Hence based on the above findings of the study, the LD50 of FAT 20042/B in rats of both sexes, observed over a period of 15 days, was estimated to be > 7000 mg/kg bw.

In a study (1974) investigating acute oral toxicity potential, FAT 20042/A was administered to groups of rats (each consisting of 5 males and 5 females) by oral gavage, at doses of 3170, 4640, 6000 and 7750 mg/kg. The treated animals were observed for mortality and clinical signs over 14 days post administration of the test substance and subjected to gross necropsy after the completion of observation period. No mortality was observed. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The surviving animals had recovered within 6 to 8 days. No substance related gross organ changes were seen. Based on the findings of the study, LD50 of FAT 20042/A in rats of both sexes, observed over a period of 15 days, was estimated to be 5514 mg/kg bw.

Inhalation:

The acute inhalation toxicity of FAT 20042/B was investigated in a study conducted according to the method of Sachsse et al. (1973, 1976). In this study, groups of young adult rats (each consisting of 10 males and 10 females) were exposed to test concentrations of 0, 877 and 1353 mg/m3. 4 hour inhalation exposure was given to the rats through tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only got exposed. Mortality, clinical signs and body weight changes were monitored throughout an observation period of 14 days and the surviving animals were subjected to the gross necropsy after the completion of observation period. Particle size distribution analysis of the chamber airborne particles showed that approximately 40 % were smaller than 7 µm in diameter. No mortality observed throughout the study. Dyspnoea, exophthalmos, ruffled fur and curved body position were observed at both doses. The animals exposed to the test material recovered within 4 days. The control rats failed to show any symptoms during the exposure and observation period. No significant change was seen with body weight and body weight gains of the exposed animals. Partially congested organs were observed at gross necropsy. based on the findings of the study, the LC50 for FAT 20042/B was estimated to be >1353 mg/m3.

Dermal:

Currently no study to assess acute dermal toxicity of Acid Red 195 is available. However, the molecular weight of the substance is 513.4-553.4 g/mol, which indicates substance is too large for dermal absorption. Further, high water solubility (250.8 g/L) and low partition coefficient (-3.30 at 20 °C), indicate the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Hence, the dermal uptake for the substance is expected to be low. Further, neither mortality nor systemic effects were observed in the acute oral toxicity studies with Acid Red 195. Owing to the high water solubility, absorption through gastro-intestinal tract through oral ingestion is considered to be the most relevant route of exposure. Since this route does not result in systemic toxicity, acute dermal exposure is considered to have negligible potential for systemic toxicity. Additionally, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected via the dermal route.Therefore testing by the inhalation route was considered scientifically not necessary and the intrinsic property/toxicity potential can be extrapolated from the data available from acute oral toxicity study.

Justification for classification or non-classification

Based on the available data from acute toxicity studies with FAT 20042, thetest substance does not meet the criteria for classification for acute toxicity according to the CLP (1272/2008) Regulation.