Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute toxicity: oral

Data on acute oral toxicity test was not available for the target substance (Reactive Red 024:1). To fill the data gaps, read across approach is adapted using similar substance Reactive Red 024. So, in a key study, an acute oral toxicity of FAT 40034 was evaluated in a limit test using Sprague-Dawley rats according to a methodology similar to OECD Guideline 401. 5 males and 5 females were administered a single dose of 5000 mg/kg bw orally. After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No clinical symptoms were recorded and no deaths occurred. At autopsy no changes caused by the administration of FAT 40034/A were seen. Based on the read across data generated from the acute oral toxicity of Reactive Red 024, the acute oral median lethal dose (LD50) of target substance (Reactive Red 024:1) is also considered to be greater than 5000 mg/kg bw. In a supporting study, an acute oral toxicity of FAT 40034 the acute oral LD50 was identified to 8600 mg/kg bw.

Acute toxicity: inhalation

Data on acute inhalation toxicity test was not available for the target substance (Reactive Red 024:1). To fill the data gaps, read across approach is adapted using similar substance Reactive Red 024. A study was performed to determine the inhalation toxicity of FAT 40034/B in Tif: RAIF (SPF) rats. 10 males and 10 females were exposed to the test concentration of 1552 mg/m³ for 4 h in a nose-only exposure system. The concentration and the particle size distribution of the dust in the vicinity of the animals was monitored at 1 h intervals throughout the dust exposure. The size distribution of the dust particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm. During the 4-h exposure period and the subsequent 14 observation days, no toxic symptoms were observed. No substance related gross organ changes were recorded at the necropsy. No mortality was seen during the study. Based on the read across data generated from the acute inhalation toxicity of Reactive Red 024, the LC50 of target substance (Reactive Red 024:1) is also considered to >1500 mg/m³ air.

Acute dermal toxicity:

Currently no study to assess acute dermal toxicity of FAT 40034 is available. However, read across substance FAT 40850 (Reactive Red 286) was evaluated for the acute toxicity via dermal route. In this GLP-compliant dermal toxicity study, performed according to OECD Guideline 402, Wistar rats (5/sex) were administered FAT 40850 at the dose of 2000 mg/kg bw. Neither mortality nor clinical signs were observed during the observation period. In all animals, strong violet staining produced by the test substance was noted on the treated skin area from test day 2 up to test day 6 or 9. However, this staining prevented the assessment of possible erythema. When assessable, no local dermal signs were observed in all animals. Under the study conditions, based on this read-across data generated with FAT 40850/A, the acute dermal median lethal dose (LD50) of Reactive Red 024:1 is also considered to be greater than 2000 mg/kg. The molecular weight of FAT 40034 is 802.1 g/mol, which indicates substance is too large for dermal absorption. The high water solubility (434 g/L) and low partition coefficient (log Pow = -3.52) of FAT 40034, 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, the absence of systemic toxicity or mortality in skin irritation as well as sensitization studies, further supports the conclusion that low acute toxicity is expected via dermal route. Taking above discussion and the results of acute dermal toxicity with source substance FAT 40850 into account, no hazard is expected in case of dermal exposure of FAT 40034, hence, further experiments to assess acute dermal toxicity are not taken into account.

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:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer chapter 13 for the detailed analogue justification.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: In-house breeding
- Age at study initiation: 5 weeks
- Weight at study initiation: 118 g
- Fasting period before study: 18 h
- Housing: caged singly
- Diet: commercial pelleted diet (Oakes Special Diet with added Vit. E) ad libitum):
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Photoperiod (hrs dark / hrs light): 12 h
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The compound (as a 50 % w/v suspension in water) was administered as a single dose by gavage to rats which had been fasted for 18 h, at a rate of 10 ml/kg equivalent to 5 g/kg of compound.
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed.
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% Cl not specified
Mortality:
no deaths occurred.
Clinical signs:
No clinical symptoms were recorded.
Body weight:
None
Gross pathology:
At autopsy no changes caused by the administration of FAT 40034/A were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of FAT 40034/A in SD rats is greater than 5000 mg/kg bw.
Executive summary:

The acute oral toxicity of FAT 40034 was evaluated in a limit test using Sprague-Dawley rats according to a methodology similar to OECD Guideline 401. 5 males and 5 females were administered a single dose of 5000 mg/kg bw orally. After administration of the compound, the animals were observed for 14 days. Deaths and clinical symptoms were recorded. At the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia and an autopsy performed. No clinical symptoms were recorded and no deaths occurred. At autopsy no changes caused by the administration of FAT 40034/A were seen. In conclusion, the acute oral median lethal dose (LD50) of FAT 40034/A in SD rats of both sexes observed over a period of 14 days is greater than 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Good quality study performed according to internationally accepted scientific principles with detailed information.

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:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer chapter 13 for the detailed analogue justification.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
traditional method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF) strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: raised on premises
- Weight at study initiation: 170 to 195 g
- Housing: 10 animals in Macrolon cages, type 4
- Diet: NAFAG, Gossau SG ad libitum
- Water: ad libitum):
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10 h light
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Remark on MMAD/GSD:
None
Details on inhalation exposure:
Testing procedures:
For inhalation the rats were kept on separate PVC tubes positioned radially around the exposure chamber such that snout and nostrils of the animals only were exposed to the dust. The exposure was started 15 minutes after onset of the dust production, when the dust had reached an even dispersal throughout the chamber. During the exposure period the relative humidity inside the chamber was 50 % RH. 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.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Remarks on duration:
None
Concentrations:
1552 (+/- 272) mg/m³
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
Dust production:
The dust was generated by injecting the test material with the help of a "Grafix Exaktomat Injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min. The concentration and the particle size distribution of the dust in the vicinity of the animals was monitored at 1 hour intervals throughout the dust exposure. The concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 um (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the dust particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 mm (Schleicher and Schuell) at an air flow rate of 17.5 L/min.
Statistics:
None
Preliminary study:
None
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 500 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed
Clinical signs:
other: During the 4-h exposure period and the subsequent 14 observation days, no toxic symptoms were observed.
Body weight:
None
Gross pathology:
The animals were submitted at random to a necropsy at the end of the observation period. No substance related gross organ changes were seen.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The 4 h LC50 of FAT 40034/B with dust exposure for rats of both sexes is greater than 1500 mg/m³ air.
Executive summary:

A study was performed to determine the inhalation toxicity of FAT 40034/B in Tif: RAIF (SPF) rats. 10 males and 10 females were exposed to the test concentration of 1552 mg/m³ for 4 h in a nose-only exposure system. The concentration and the particle size distribution of the dust in the vicinity of the animals was monitored at 1 h intervals throughout the dust exposure. The size distribution of the dust particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with a pore size of 0.2 µm. During the 4-h exposure period and the subsequent 14 observation days, no toxic symptoms were observed. No substance related gross organ changes were recorded at the necropsy. No mortality was seen during the study. Based on the findings of the study, the LC50 of a 4 h dust exposure for rats of both sexes is greater than 1500 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:
1 500 mg/m³
Quality of whole database:
Good quality study performed according to internationally accepted scientific principles with detailed information.

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:
2010-01-05 till 2010-01-26
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Swiss GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: TZ 5978 / BOP 07-09
- Expiration date of the lot/batch: 31-Jul-2014

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5 °C), light protected.
- Stability under storage conditions: Stable under storage conditions
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS RccHan: WIST(SPF)
- Source: Harlan Laboratories B.V. Kreuzelweg 53 5961 NM Horst / The Netherlands Postbus 6174 5960 AD Horst / The Netherlands
- Age at study initiation: Males: 9 weeks, Females: 11 weeks
- Weight at study initiation: Males 244.8 - 261.9 g ; Females: 191.8 - 210.3g
- Fasting period before study: no data
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 30/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water: Community tap water from Füllinsdorf ad libitum.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): relative humidity between 30-70 (values above 70% during cleaning process possible)
- Air changes (per hr): Air-conditioned with 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 h light and 12 h dark, music during the daytime light period.

Type of coverage:
semiocclusive
Details on dermal exposure:
TEST SITE
- Area of exposure: no data
- % coverage: approx. 10 % of the body surface
- Type of wrap if used: skin with a syringe and covered with a surgical gauze pad (ca. 5 x 5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, flushed with lukewarm water and drapped off with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL AND VEHICLE
- Amount(s) applied (volume or weight with unit): 6 mL/kg
- Concentration (if solution): dose: 2000 mg/kg BW
- Constant volume or concentration used: yes
- test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight:volume).
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Viability / Mortality: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.

Clinical Signs: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.

Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15 using the numerical scoring system described in Appendix I.

Body Weights: On test days 1 (prior to administration), 8 and 15.

- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs were performed. The appearance of any macroscopic abnormalities was recorded.No organs or tissues were retained.
Statistics:
No statistical analysis was used.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no statistical analysis was performed
Mortality:
No intercurrent deaths occurred during the course of the study.
Clinical signs:
No clinical signs were recorded throughout the complete observation period.
Body weight:
The body weight of the animals was considered to be within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
In all animals, strong violet staining produced by the test item was noted on the treated skin area from test day 2 up to test day 6 (males) or 9 (females). However, this staining prevented the assessment of a possible erythema. When assessable, no local dermal signs were observed in all animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose (LD50) of FAT 40850/A after single dermal administration to Wistar rats of both sexes is greater than 2000 mg/kg body weight.
Executive summary:

Five male and five female Wistar rats were treated with FAT 40850/A TE at 2000 mg/kg by dermal application in accordance with OECD guideline 402 and EU Method B.3 and GLP. The test item was formulated in purified water at a concentration of 0.33 g/mL and administered at a volume dosage of 6 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2-15. Local signs were evaluated once daily after removal of the dressing on test day 2 up to test day 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the complete observation period. In all animals, strong violet staining produced by the test item was noted on the treated skin area from test day 2 up to test day 6 or 9. However, this staining prevented the assessment of possible erythema. When assessable, no local dermal signs were observed in all animals. The body weight of all animals was considered to be within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy. The median lethal dose (LD50) of FAT 40850/A after single dermal administration to Wistar rats of both sexes is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study conducted on a read across substance FAT 40850 in accordance to OECD guideline 402 and GLP.

Additional information

Justification for classification or non-classification

Based on the results in the acute oral and inhalation along with results from dermal toxicity study with read-across substances, Reactive Red 024:1 does not considered to be classified according to according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Categories Display