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Description of key information

The median lethal dose of FAT 93504/A after single oral administration to rats of both sexes, observed over a period of 14 days was determined to be >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:
31-JAN-2000 to 1-MAR-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanIbm: WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Test system: Rat, Hanlbm: WIST (SPF)
-Rationale: Recognized by the international guidelines as a recommended test system.
-Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wölferstrasse 4, CH-4414 Füllinsdorf / Switzerland.
-Number of animals per group: 3 males and 3 females.
-Total number of animals: 3 males and 3 females.
-Age when treated: Males: 8 - 10 weeks, Females: 8 - 10 weeks.
-Body weight range when treated: Males: 183 - 206.4 g and Females: 138.7 - 139.7 g
-Identification: By unique cage number and corresponding color-coded spots on the tail.
-Acclimatization: One week under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

HUSBANDRY
- Room N°: 104 / RCC Ltd, Füllinsdorf.
- Conditions: Standard Laboratory Conditions
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a target range for room temperature of 22 ± 3 °C, and for relative humidity between 32-45 %. The animals were provided with a 12-hour artificial fluorescent light, 12-hour dark cycle. Music was played during the light period.
- Accommodations: Groups of three in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).
- Diet:Pelleted standard Kliba 3433, batch nos. 40/99 and 43/99 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation). Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water: Community tap water from Füllinsdorf, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
Route of administration:
oral: gavage
Vehicle:
other: PEG 300
Details on oral exposure:
The animals received a single dose of the test article on a 2000 mg/kg bw basis by oral gavage following fasting for approximately 18 (males) to 24 (females) hours, but with free access to water. Food was provided again approximately 3 (males) to 4 (females) hours after dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
OBSERVATIONS:
- Duration of observation period following administration: 14 days.
- Mortality / Viability: One, two, three and five hours after test article administration on test day 1 and once daily for surviving animals during days
2-15.
- Body weights: On test days 1 (pre-administration), 8 and 15 for surviving animals.
- Clinical signs: Each animal was examined for changes in appearance and behaviour four times during day 1, and once daily for surviving animals
during days 2-15. All abnormalities were recorded.
- Necropsy: Animals which died spontaneously during the observation period were necropsied as soon as they were found dead. At the end of the observation period all surviving animals were sacrificed by intraperitoneal injection of NARCOREN at a dose of at least 2.0 ml/kg bw. The animals were examined macroscopically and all abnormalities recorded.
Statistics:
The toxicity was estimated without the 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:
The following mortality was observed:
- Males: 0 % (no mortality)
- Females: 33 % (1 out of 3)
Clinical signs:
other: Ruffled fur was observed on test day one in all male animals. Ruffled fur, weak activity and/or emaciation were noted in all females from test day 5 to test day 11. Red to light red urine was observed in the cage of the male and female animals.
Gross pathology:
Dark red discoloration of the digestive system was observed at the unscheduled necropsy of one female. No macroscopic findings were observed at scheduled necropsy.

None

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose of FAT 93504/A after single oral administration to rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.
Executive summary:

The purpose of this was to assess the acute oral toxicity of FAT 93504/A when administered by single oral gavage to rats, followed by an observation period of 14 days.

This experiment was done according to the OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). This study should provide a rational basis for risk assessment.

Two groups, each using three male or three female Hanlbm: WIST (SPF) rats was treated with FAT 93504/A at 2000 mg/kg by oral gavage. The test article was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

The following animals were treated and percentage mortality was observed:

Group 1: (2000 mg/kg bw)

Males: 0 %

Females: 33 %

One female died spontaneously on test day 9.

Ruffled fur was observed on test day one in all male animals. Ruffled fur, weak activity and/or emaciation were noted in all females from test day 5 to test day 11. Red to light red urine was observed in the cage of the male and female animals.

All three females showed a marked loss of body weight (23.7, 26.5 and 28 %) one week after treatment. The body weight of the males was within the range commonly recorded for animals of this strain and age. Dark red discoloration of the digestive system was observed at the unscheduled necropsy of one female. No macroscopic findings were observed at scheduled necropsy.

In conclusion, the median lethal dose of FAT 93504/A after single oral administration to rats of both sexes, observed over a period of 14 days is >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 GLP study.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

The acute toxicity of FAT 93504/A was evaluated according to the OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). Two groups, each using three male or three female Hanlbm: WIST (SPF) rats was treated with FAT 93504/A at 2000 mg/kg by oral gavage. One female died spontaneously on test day 9. Ruffled fur was observed on test day one in all male animals. Ruffled fur, weak activity and/or emaciation were noted in all females from test day 5 to test day 11. Red to light red urine was observed in the cage of the male and female animals. Dark red discoloration of the digestive system was observed at the unscheduled necropsy of one female. No macroscopic findings were observed at scheduled necropsy.

In conclusion, the median lethal dose of FAT 93504/A after single oral administration to rats of both sexes, observed over a period of 14 days is >2000 mg/kg bw.


Acute toxicity: inhalation

Currently no study to assess acute inhalation toxicity of Disperse Red 302:1 is available. The substance has low volatility owing to its vapour pressure (4.65 × 10E-11 Pa at 20 °C), so the potential for the generation of inhalable forms is considered to be low. 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. Further, absence of mortality as well as adverse systemic effects in the acute oral toxicity study, suggests the substance to have low toxicity on acute inhalation exposure. Hence no significant toxicity is expected via the inhalation route and safety for human health can be estimated via route to route extrapolation. Taking into consideration all the above arguments, no acute inhalation toxicity study was performed.

Acute toxicity: dermal

Currently no study to assess acute dermal toxicity of Disperse Red 302:1 is available. However, the substance has very low solubility in water (3.7 µg/L), hence dermal uptake is likely to be low as the substance is considered as not sufficiently soluble in water to partition from the stratum corneum into the epidermis. Further absence of mortality as well as adverse systemic effects in the acute oral toxicity study, suggests the substance to have low toxicity on acute dermal exposure. Similarly, absence of systemic toxicity or mortality in skin irritation as well as skin sensitization studies, supports the conclusion that no adverse effects are expected via dermal route. Further experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the test item only show up upon dermal exposure and not after systemic application. Hence no significant toxicity is expected via the dermal route and safety for human health can be estimated via route to route extrapolation. Hence further experiments to assess acute dermal toxicity are not taken into account.

Justification for classification or non-classification

Based on the available data, Disperse Red 302:1 does not need classification for acute toxicity as per the Regulation (EC) No. 1272/2008 (CLP) criteria.