Registration Dossier

Administrative data

Description of key information

The substance was found to have acute oral as well as dermal LD50 values of >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:
Test start date: 06 December, 1989; Test end date: 27 December 1989; Study completion date: 21 February, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Substance identified as: FAT 31064/F
- Batch No.: EN 158496.82 / HEW 133/6
- Description: Powder
- Stability of test article: stable; expiration date: November 1994
- Stability of test article dilution: stable for at least 2 hours
- Safety Precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety.
Species:
rat
Strain:
Wistar
Remarks:
Han. (outbred, SPF-quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Füllinsdorf
- Initial body weight range: males: 196 - 199 g, females: 165 - 178 g
- Initial age: males: 9 weeks, females: 11 weeks

Husbandry:
Standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour, and hourly monitored environment with temperature 22+/-3 °C, relative humidity 40-70 %, 12 hours artificial fluorescent light/12 hours dark, music/light period.
Diet: Pelleted standard Kliba 343, Batch 60/89 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.
Water: Community tap water from Itingen.
Acclimatisation: One week under laboratory conditions, after veterinary examination.
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled
Details on oral exposure:
TEST ARTICLE PREPARATION
The test article was placed into a glass beaker on a tared Mettler PE 360 balance, and the vehicle, (bi-distilled water) was added. A weight by volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, D-7813 Staufen).
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke and Kunkel, D-7813 Staufen). The preparation was made immediately prior to each dosing.

TREATMENT
The animals received a single dose of the test article on a mg/kg body weight base by oral gavage after being fasted for 12 to 18 hours (access to water was not interrupted). Food was again presented approximately three hours after dosing.
Application Volume/kg body weight: 10 mL at 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Mortality: Four times during test day 1, and daily during days 2 - 15.
- Body Weights: Test days 1 (pre-administration), 8 and 15.
- Clinical Signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsies were performed by experienced prosectors. All animals were necropsied. The surviving animals were killed by intraperitoneal injection of sodium pentobarbitone.
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A female was found dead on day 6 after treatment.
Clinical signs:
The following systemic symptoms were observed:
males - no systemic symptoms were observed.
females - rales.
The surviving female rats had recovered after 2 hours.
Body weight:
The body weight gain of the surviving animals was not affected by the test article treatment throughout the entire study period.
Gross pathology:
The following macroscopical organ changes were observed in the female found dead:
2000 mg/kg: dead - lungs: discoloration, dark red.
stomach: distended with gas.
liver: discoloration, black-brown.
sacrificed - no findings noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of FAT 31064/F was determined to be >2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test substance was evaluated in a study conducted according to OECD Guideline 401 and EU Method B.1. Wistar Han. (outbred, SPF-quality) rats were used for this experiment. A limit test was performed with the dose being 2000 mg/kg bw. A group of rats, containing 5 males and 5 females, was administered the test substance via oral gavage. A female was found dead on day 6 after treatment. No systemic symptoms were observed in treated males. Two out 5 females had rales. The surviving female recovered in 2 hours after treatment. No effect on body weight changes were seen. No deviations from normal morphology were seen in surviving animals at the necropsy. Based on these findings, the LD50 of the test substance was determined to be >2000 mg/kg bw.

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

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
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

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Test start date: 06 December, 1989; Test end date: 27 December, 1989; Study completion date: 27 February 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Substance identified as: FAT 31064/F
- Batch No.: EN 158496.82 / HEW 133/6
- Description: Powder
- Stability of test article: Stable; expiration date: November 1994
- Stability of test article dilution: Stable for at least 2 hours
- Safety Precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety.
Species:
rat
Strain:
Wistar
Remarks:
Han. (outbred, SPF-quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414 Füllinsdorf
- Initial body weight range: males: 219 - 230 g, females: 195 - 204 g.
- Initial age: males: 10 weeks, females: 12 weeks

Husbandry:
Standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour and hourly monitored environment with temperature 22+/-3 degrees centigrade, relative humidity 40-70 %, 12 hours artificial fluorescent light/12 hours dark, music/light period.

Diet:
Pelleted standard Kliba 343, Batch 60/89 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum.

Water: Community tap water from Itingen.

Acclimatisation: One week under laboratory conditions, after veterinary examination.
Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Bi-distilled
Details on dermal exposure:
TEST ARTICLE PREPARATION
The test article was placed into a glass beaker on a tared Mettler PE 360 balance and the vehicle (bi-distilled water) was added. A weight/volume dilution was prepared using a homogenizer (Ultra-Turrax, Janke and Kunkel, D-7813 Staufen).
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer (Janke and Kunkel, D-7813 Staufen).
The preparation was made immediately prior to each dosing.

TREATMENT
Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10 % of the total body surface.
On test day 1 the test article was applied evenly on the skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Twenty-four hours after the application, the dressing was removed. The treated skin was washed with lukewarm tap water, dried with disposable paper towels and the skin reaction was assessed according to the method of Noakes and Sanderson (Noakes, D.N. and Sanderson, D.M. "A Method for Determining the Dermal Toxicity of Pesticides". Brit. J. Industr. Med., 26, 59-64, 1969).

Application volume/ kg body weight: 4 mL at 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw (single application)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
OBSERVATIONS
Mortality / Viability: Four times during test day 1, and daily during days 2-15.
Body Weights: Test days 1 (pre-administra'tion), 8 and 15.
Clinical Signs:
Each animal had an examination for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded. Due to the 24-hour semi-occlusive treatment, the local findings were observed starting with day 2 of test.

Necropsy: Necropsies were performed by experienced prosectors. All animals were necropsied. All animals were killed by intraperitoneal injection of sodium pentobarbitone.
Statistics:
The LOGIT-Model could not be applied to the observed rate of death. The toxicity was estimated without use of a statistical model.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortaility was observed.
Clinical signs:
The following local signs were observed:
All treated males - skin/fur: skin blue (back);
females - skin/fur: skin blue (back) (for all 5); scales (back) ( for a single female).
The animals showing scales had recovered after 12 observation days. Blue discoloration of the treated skin was observed until termination of observation. No systemic signs were observed.
Body weight:
Female no. 6 showed loss of weight between days 1 and 8 of test. The body weight gain of the other animals were not affected throughout the study by test article treatment
Gross pathology:
No macroscopical organ changes were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 of FAT 31064/A was determined to be >2000 mg/kg bw.
Executive summary:

The acute dermal toxicity potential of FAT 31064/A was assessed in a study carried out in accordance with OECD Guideline No. 402, "Acute Dermal Toxicity" and EEC Directive 92/69/EEC, Part B.3, "Acute Toxicity - Dermal". In this study, the test substance was administered to five rats of each sex by dermal application at 2000 mg/kg bw for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. No systemic symptoms were seen. Bluish skin on back was observed after the removal of the patches in all exposed animals. Female no. 6 showed loss of weight between days 1 and 8 of test. The body weight gain of the other animals were not affected throughout the study by test article treatment. No macroscopical organ changes were noted during the necropsies. Based on the findings of the study, the acute dermal LD50 for FAT 31064/A was determined to be >2000 mg/kg bw.

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

Additional information

Oral:

The acute oral toxicity of the test substance was evaluated in a study conducted according to OECD Guideline 401 and EU Method B.1. A limit test was performed with the dose being 2000 mg/kg bw. A group of rats containing 5 males and 5 females was treated with the test substance via oral gavage. A female was found dead on day 6 after treatment. No systemic symptoms were observed in treated males. Two out 5 females had rales. The surviving female recovered in 2 hours after treatment. No effect on body weight changes were seen. No deviations from normal morphology were seen in surviving animals. Hence, based on these findings, the LD50 of the test substance was determined to be >2000 mg/kg bw. The substance was further evaluated in a number studies, which support the conclusion that the substance has low acute oral toxicity, with LD50 being greater than 5000 mg/kg bw in all these studies.

Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Basic Blue 145 is available. However, the vapour pressure for the substance was estimated to be 0.000061 Pa at 20 °C. Hence the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, 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. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, 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 expected low volatility of the substance, the fact that the chemical is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further, the chemical is found to have water solubility of 180 g/L, hence in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared, thereby further limiting the absorption. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50: >2000 mg/kg bw), with no mortality or systemic toxicity being seen upto 2000 mg/kg bw, hence it does not need to be classified STOT SE and low toxicity is expected for this chemical via the inhalation route. Taking above arguments into account, low toxicity potential is expected on acute exposure of Basic Blue 145 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Dermal:

The acute dermal toxicity potential of the substance was assessed in a study carried out in accordance with OECD Guideline No. 402, "Acute Dermal Toxicity" and EEC Directive 92/69/EEC, Part B.3, "Acute Toxicity - Dermal". In this study, the test substance was administered to five rats of each sex by dermal application at 2000 mg/kg bw for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. No systemic symptoms were seen. Bluish skin on back was observed after the removal of the patches in all exposed animals. Female no. 6 showed loss of weight between days 1 and 8 of test. The body weight gain of the other animals were not affected throughout the study by test article treatment. No macroscopical organ changes were noted during the necropsies. Hence, based on the findings of the study, the acute dermal LD50 for FAT 31064/A was determined to be >2000 mg/kg bw.

Justification for classification or non-classification

Based on the available information, the substance has low acute toxicity and does not warrant classification as per CLP (Regulation EC No. 1272/2008) criteria.