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Description of key information

Based on the data it can be concluded that the test substance FAT 20004 is found to non-toxic by inhalation and dermal route, but toxic by oral route.

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:
Experiment start date - 17 August 1995; Experiment end date - 27 September 1995; Study completion date - 19 October 1995.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The relative humidity in the animal room transiently exceeded the targeted range of 40-70 %.
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
The relative humidity in the animal room transiently exceeded the targeted range of 40-70 %.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Identification: TECTILON GELB 4R ROH, FEUCHT LABORGETROCKNET (FAT 20004/I) [crude, lab dried)
Description: Red orange powder
Batch Number: P3+4 PM
Purity/Formulation: ca 90 %
Stability of Test Article: Stable under storage condition; expiration date: Sep 1998
Storage Conditions: In the original container at room temperature from direct sunlight.
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wölferstrasse 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: males: females 9-10 weeks, Males 7-8 weeks
- Housing:Groups of five in Makrol on type-4 cages with autoclaved standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, Batch nos. 86/95 and 65/95 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst)
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum
- Acclimation period: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 23 °C
- Humidity (%): 47 - 76 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark (light period between 6.00 a.m. to 6.00 p.m.), music during the light period.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Bi-distilled
Details on oral exposure:
DOSE FORMULATION
The test article was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke & Kunkel, D-79219 Staufen).
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke & Kunkel, D-79219 Staufen).
The preparation was made shortly before dosing.


TREATMENT
The animals received a single dose of the test article on a mg/kg body weight basis by oral gavage following fasting for approximately 16 hours, but with free access to water. Food was provided again approximately 3 hours after dosing.

Rationale: Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test article
Doses:
100 mg/kg (Group 1)
1000 mg/kg (Group 2)
2000 mg/kg (Group 3)
No. of animals per sex per dose:
5 males- 5 female per group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality.
Statistics:
The LOGIT-Model (COX, Analysis of Binary Data, London 1977) was used to calculate the mean lethal dose. The 90 %, 95 % and 99 % confidence limits for the toxicity value and the slope of the dose response line were calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
428.55 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived until the end of the study period.
Clinical signs:
No clinical signs of toxicity were observed during the observation period in all animals of all groups. Except of one animal of group 2 (no. 20) which showed sedation, hunched posture, dyspnea and ruffled fur.
Body weight:
The body weight of the animals was within the normal range for rats of this strain and age for all surviving animals.
Gross pathology:
In the male and female animals of group 1 no macroscopic findings were observed. In the male and female animals of group 2 the thoracic cavity contained watery fluid and in the jejunum, black-brown contents (males) were observed. In the male and female animals of group 3 the thoracic cavity contained watery fluid (males); distended stomach and black-brown contents in the jejunum were observed, the females showed dark red discoloration of the lungs.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The mean lethal dose (LOGIT-model) for the acute oral toxicity of FAT 20004/I in rats of both sexes observed for a period of 14 days is: LD50: 428.55 mg/kg
Executive summary:

The purpose of this study was to assess the acute oral toxicity of FAT 20004/I when administered by single oral gavage to rats, followed by an observation period of 14 days. The test article was administered to groups of 5 male and 5 female rats by oral gavage, at single doses of 100 mg, 1000 mg and 2000 mg/test article/kg body weight. No clinical signs of toxicity were observed during the observation period in all animals of all groups. Except of one animal of group 2 which showed sedation, hunched posture, dyspnea and ruffled fur. The body weight of the animals was within the normal range for rats of this strain and age for all surviving animals. In the male and female animals of group 1 no macroscopic findings were observed. In the male and female animals of group 2 the thoracic cavity contained watery fluid and in the jejunum, black-brown contents (males) were observed. In the male and female animals of group 3 the thoracic cavity contained watery fluid (males); distended stomach and black-brown contents in the jejunum were observed, the females showed dark red discoloration of the lungs. Based on these observations, the mean lethal dose (LOGIT-model) for the acute oral toxicity of FAT 20004/I in rats of both sexes observed for a period of 14 days is: LD50: 428.55 mg/kg


For Males: 367.63 mg/kg


For Females: 469.40 mg/kg

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
428.55 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:
Study completion date - 02 August 1976.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Test Material: MA 23, D 956
Species:
rat
Strain:
other: Charles River Rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: Housed individually in stock cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Test animals were exposed in a specially constructed inhalation chamber. The chamber was designed so that the animals could be introduced into the test atmosphere after the desired dust concentration was established. Each animal was caged separately during exposure to minimize filtration of inspired air by animal fur. Dust was suspended with a specially designed dust feeder capable of producing high concentrations over a long period of time. The test material powder was passed through a high-velocity stream of clean, dry air (-40 °C dewpoint). The air-jet velocity was adjusted to obtain the desired concentration of suspended dust. The test atmosphere was then introduced into the exposure chamber at the top center, dispersed by a baffle plate and exhausted at the bottom of the chamber. Air flow rate through the system was measured with a rotameter connected in the air supply line upstream of dust contamination. The rotameter was calibrated with a wet-test meter after the exposure was completed.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
193.8, 850, 2850 mg/m³ air
No. of animals per sex per dose:
5 animals per group
Control animals:
yes
Details on study design:
Dust was suspended with a specially designed dust feeder capable of producing high concentrations over a long period of time. The test material powder was passed through a high-velocity stream of clean, dry air (-40 °C dewpoint). The air-jet velocity was adjusted to obtain the desired concentration of suspended dust. The test atmosphere was then introduced into the exposure chamber at the top center, dispersed by a baffle plate and exhausted at the bottom of the chamber. Air flow rate through the system was measured with a rotameter connected in the air supply line upstream of dust contamination. The rotameter was calibrated with a wet-test meter after the exposure was completed. The concentration of test material dust present in the exposure chamber was determined by sampling the test atmosphere in the breathing zone of the animals being exposed. The total weight of dust collected on a glass fiber filter was divided by the total volume of air drawn through the filter during the sampling period. Air flow rate for sampling was regulated by a calibrated Limiting orifice. The average analytical concentration of airborne dust was obtained by repeated air sampling. A sample of airborne dust was collected from the exposure chamber for the purpose of conducting a microscopic determination of particle size distribution. Particles were counted with respect to 4 size ranges, viz., 5 microns or smaller, 6 to 10 microns, 11 to 25 microns and larger than 25 microns. Particles less than 10 microns are generally considered to be respirable. The smallest particle which can be detected by the light-field technique employed is approximately 1µm. The largest particle observed was also recorded.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
873.1 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All deaths occurred between 8 and 18 hours after exposure.
Clinical signs:
other: The only reaction observed during the 3 exposures was hypoactivity.
Body weight:
Body weight gains for all surviving animals were within the normal limits.
Gross pathology:
No gross tissue changes attributable to the effects of the test material were observed in any of the rats that survived to completion of the study.

Result:


 




































Group No Total Number of Animals      Male/ FemaleNominal Concentration

Mortality


Male-Female



Weight Gain


Male-Female (grams)


 
15 /5193.8 mg/m³ air0/5 - 1/582.-48
25 /5850.0 mg/m³ air4/5 - 3/594-36
35 /52850.0 mg/m³ air3/5 - 4/567-31
Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of a 4 hour aerosol exposure for rats of both sexes is 873.1 mg/m³ air, when evaluated for a 14-day post treatment observation period.
Executive summary:

The acute inhalation toxicity test was performed with young adult rats. This study was conducted according to method similar or equivalent to OECD test guideline 403. 4 hour inhalation exposure was given to rats by specially constructed inhalation chamber of the animals. Body weight, clinical signs, mortality were monitored throughout an observation period of 14 days. The LC50 of a 4-hours aerosol exposure for rats of both sexes is 873.1 mg/m³ air, when evaluated for a 14 day post-treatment observation period.

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

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study completion date - 06 October 1976.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Housing: The rabbits were housed individually in suspended, wire-bottomed cages and maintained on a standard laboratory.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All rabbits had been maintained under observation in the laboratory for at least seven days prior to testing.

Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:

TEST SITE
- Area of exposure: Twenty-four hours prior to the dermal applications, the backs of the rabbits were shaved free of hair with electric clippers.
- % coverage: The shaved area on each animal constituted about 30 percent of the total body surface area.
- Type of wrap if used: The test site was covered by wrapping the trunk of the animal with impervious plastic sheeting which was securely taped in place

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: after 24 hours

Duration of exposure:
24 hours
Doses:
3000 mg/kg body weight
No. of animals per sex per dose:
4 animals/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
No statistical analysis was used.
Preliminary study:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weights were recorded on day 0, 7 & 14 of the test.
Gross pathology:
No macroscopic findings were observed at necropsy.
Other findings:
None

Mortality & Body Weight Data:

Dose level (mg/kg) Animal Number & Sex Individual Body Weights (kg) Number Dead Percent Dead
0 7 14 Number Tested
3,000 1 - M* 2.7 2.88 3.02 0/4 0
2 - M 2.7 3.08 3.08
3 - F* 2.8 3.1 3.1
4 - F 2.68 2.86 2.86
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of FAT 20004 after single dermal administration to rabbits of both sexes, observed over a period of 14 days is: LD50 (rabbit): >3000 mg/kg body weight.
Executive summary:

A key study was performed to determine the acute dermal toxicity of FAT 20004 on New Zealand rabbits over a period of 14 days. The test substance was applied at a dose of 3000 mg/kg body weight. The test site was covered by wrapping the trunk of the animal with impervious plastic sheeting which was securely taped in place. The test material remained in contact with the skin for 24 hours. At the end of this period, the plastic sheeting and all residual test material were removed. The test sites were examined for local skin reactions and the animals were returned to their cages. Observations for mortality, local skin reactions, and behavioral abnormalities were continued for a total of 14 days following the skin applications. Initial, 7 and 14-day body weights were recorded. A necropsy examination was conducted on all animals. No pharmacotoxic symptoms were observed in the rabbits following dermal exposure to FAT 20004. The material stained the skin of the albino rabbit. Due to this, skin reactions (erythema or burns) at 24 hours could not be evaluated. No skin changes were noted at 7 and 14 days. Necropsy examination did not reveal any gross pathologic alterations. The median lethal dose of FAT 20004 after single dermal administration to rabbits of both sexes, observed over a period of 14 days is: LD50 (rabbit): >3000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw

Additional information

A GLP-compliant study was performed to assess the acute oral toxicity of FAT 20004/I when administered by single oral gavage to rats, followed by an observation period of 14 days according to OECD Guideline 401 (Acute Oral toxicity). The test article was administered to groups of 5 male and 5 female rats by oral gavage, at single doses of 100 mg, 1000 mg and 2000 mg/test article/kg body weight. No clinical signs of toxicity were observed during the observation period in all animals of all groups. Except of one animal of group 2 which showed sedation, hunched posture, dyspnoea and ruffled fur. The body weight of the animals was within the normal range for rats of this strain and age for all surviving animals. In the male and female animals of group 1 no macroscopic findings were observed. In the male and female animals of group 2 the thoracic cavity contained watery fluid and in the jejunum, black-brown contents (males) were observed. In the male and female animals of group 3 the thoracic cavity contained watery fluid (males); distended stomach and black-brown contents in the jejunum were observed, the females showed dark red discoloration of the lungs. Based on these observations, the mean lethal dose (LD50) for the acute oral toxicity of FAT 20004/I in rats of both sexes observed for a period of 14 days is 428.55 mg/kg.


In a supporting study carried out in 1978 on FAT 20004/D, the LD50 value in rats of both sexes observed over a period of 14 days is 3510 mg/kg. In several other supporting studies carried out in 1976 on FAT 20004, the LD50 values in rats of both sexes observed over a period of 14 days are 1600, 2200, 2500 mg/kg and the LD50 value for 20004/C was found to be 10,770 mg/kg.


In several other supporting studies carried out in 1975 on FAT 20004, the LD50 value in rats of both sexes observed over a period of 14 days is 5580 mg/kg and the LD50 value for 20004/B was found to be 960 mg/kg. In one of the supporting study carried out in 1973 on FAT 20004, the LD50 was found to be 1348 mg/kg. Considering the results and the LD50 values from the above studies, FAT 20004 is found to be acute toxic via oral route.


 


A study was performed to determine acute inhalation toxicity test with young adult rats. 4 hour inhalation exposure was given to rats by specially constructed inhalation chamber of the animals, body weight, clinical signs, mortality were monitored throughout an observation period of 14 days. The LC50 of a 4 hour aerosol exposure for rats of both sexes is 873.1 mg/m³ air, when evaluated for a 14-days posttreatment observation period. In several other supporting studies carried out in 1976, the LC50 of a 4 hour aerosol exposure for rats of both sexes were found to be >7170, >1314 & <590  mg/m³ air, when evaluated for a 14 day post-treatment observation period. In a supporting study carried out in 1975, the LC50 of a 4-hours aerosol exposure for rats of both sexes is >1635 mg/m³ air, when evaluated for a 14-day posttreatment observation period. Considering the LC50 values and the results obtained in the above studies, FAT 20004 is found to be not toxic via inhalation route.


 


A study was performed to determine the acute dermal toxicity of FAT 20004 on New Zealand rabbits over a period of 14 days. The test substance was applied at a dose of 3000 mg/kg body weight. The test site was covered by wrapping the trunk of the animal with impervious plastic sheeting which was securely taped in place. The test material remained in contact with the skin for 24 hours. At the end of this period, the plastic sheeting and all residual test material were removed. The test sites were examined for local skin reactions and the animals were returned to their cages. Observations for mortality, local skin reactions, and behavioral abnormalities were continued for a total of 14 days following the skin applications. Initial, 7 and 14-day body weights were recorded. A necropsy examination was conducted on all animals. No pharmacotoxic symptoms were observed in the rabbits following dermal exposure to FAT 20004. The material stained the skin of the albino rabbit. Due to this, skin reactions (erythema or burns) at 24 hours could not be evaluated. No skin changes were noted at 7 and 14 days. Necropsy examination did not reveal any gross pathologic alterations. The median lethal dose (LD50) of FAT 20004 after single dermal administration to rabbits of both sexes, observed over a period of 14 days is >3000 mg/kg body weight. In another supporting study carried out in 1975, the median lethal dose (LD50) of FAT 20004 after single dermal administration to rabbits of both sexes, observed over a period of 14 days is >3000 mg/kg body weight. Considering the results and the LD50 values obtained in the above studies, FAT 20004 is found to be not toxic via dermal route.

Justification for classification or non-classification

Acid Yellow 219 is found to be not toxic by inhalation and dermal route, hence does not require classification for these routes, but will warrant classification as acute oral cat 3 based on the oral LD50 of 428.55 mg/kg bw in accordance with Regulation (EC) No. 1272/2008.