Propanenitrile, 3-[[4-[[5,6(or 6,7)-dichloro-2-benzothiazolyl]azo]phenyl]ethylamino]-

Endpoint summary

Description of key information

The acute median lethal oral dose (LD₅₀) to rats of Disperse Red 153 is above 2000 mg/kg body weight.

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:

14 February 2022 to 11 March 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Animal Information
Species: Rat
Strain: Wistar Han TM
Source: Janvier Labs
CS4105 Le Genest Saint Isle
53941 Saint Berthevin Cedex / France
Sex: Female
Other: Females were nulliparous and non-pregnant
Number of animals for
the pre-test: 1 female
Number of animals for
the main study: 4 females
Age (beginning of treatment): 8 - 12 weeks
Body weight: see Appendix 2
Identification: The animals were distributed into the test groups at random. If possible, all animals belonging to the same experimental group were kept in one cage. The animals were individually marked by fur clippings. A colour-coded card was prepared for each project, giving details of the test type, project number, treatment start, dose level, sex and number of animals.
Acclimatization: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.

Husbandry
Housing: groups of one to five rats (of the same sex and dose group)
Cage Type: Makrolon Type IV, with wire mesh top
Bedding: granulated soft wood bedding
Feed: 2018C Teklad Global 18% protein rodent diet
(certified), ad libitum
(except for overnight fasting prior to dosing; diet was returned immediately after dosing was complete)
Water: tap water, ad libitum
Environment: temperature 22 + 2°C
relative humidity approx. 45-65%
(with the aim of 50 – 60%)
artificial light 6.00 a.m. - 6.00 p.m.
ventilation: at least eight air changes per hour
Environmental enrichment: provided throughout the study period (e.g., wooden chew blocks, fun tunnels or suitable nesting material)

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Dose administration was twice orally by gavage (feeding needle). As a single dose was not possible the dose was given in two smaller fractions over a period not exceeding 24 hours. The volume administered did not exceed 10 mL/kg b.w. for each treatment.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Details on study design:

Dose Administration
Dose administration was twice orally by gavage (feeding needle). As a single dose was not possible the dose was given in two smaller fractions over a period not exceeding 24 hours. The volume administered did not exceed 10 mL/kg b.w. for each treatment.
Based on available information on the toxicity of the test item 2000 mg/kg body weight was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.
One single animal was treated twice (not exceeding 24h).
In the absence of mortality or toxicity at a dose level of 2000 mg/kg body weight (in fractions of 2 x 1000 mg/kg over a period not exceeding 24h), an additional group of four animals was treated twice.
A total of five animals were therefore treated at a dose level of 2000 mg/kg body weight (2 x 1000 mg/kg) in the study.

Serial Observations
Morbidity/Mortality Inspection and Clinical Observations
Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after each application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing), thereafter at least once daily for 14 days. All animals were observed for 14 days after dosing.
The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation for all individual animals. Observations included changes in the skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.

Fate of the Animals
Animals were sacrificed by carbon dioxide asphyxiation followed by cervical dislocation.

Determination of Body Weight
Body weights were recorded on Day -1 (prior to dosing), Day 0 (prior to dosing), Day 7, and 14, or (if applicable) at death (unscheduled).

Terminal Investigations
Necropsy
A gross necropsy was performed on all animals that died or were humanely killed during the study (if applicable) and at the end of the in-life part. Any macroscopic abnormalities were recorded. Routinely no organs or tissues were retained.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No deaths occurred

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

The animals showed expected gains in body weight over the observation period.

Gross pathology:

The fur of all animals was slightly stained reddish. The large intestines (two animals) and caecum (two animals) were slightly filled with air. White dots were obseverd on the spleen of one animal. The thymus of one animal was slightly enlarged. Two animals showed an accumulation of fatty tissue in the abdomen.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) to rats of Disperse Red 153 was demonstrated to be greater than 2000 mg/kg body weight.

Executive summary:

Following a sighting test at a dose level of 2000 mg/kg b.w. (2 x 1000 mg/kg applied in two fractions over a period not exceeding 24 hours) in one fasted female rat, a further group of four fasted females was given an oral dose of 2000 mg/kg b.w. (2x 1000 mg/kg b.w. as fractions) of Disperse Red 153, as a formulation in corn oil. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.

Clinical Observations: Transient piloerection, partially closed eyes, decreased activity, ataxia, and slight staining of the ears, paws, and fur were observed. 

Body Weight: All animals showed expected gains in body weight.

Necropsy: The fur of all animals was slightly stained reddish. The large intestines (two animals) and caecum (two animals) were slightly filled with air. White dots were obseverd on the spleen of one animal. The thymus of one animal was slightly enlarged. Two animals showed an accumulation of fatty tissue in the abdomen.

The acute median lethal oral dose (LD₅₀) to rats of Disperse Red 153 was demonstrated to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Following a sighting test at a dose level of 2000 mg/kg b.w. (2 x 1000 mg/kg applied in two fractions over a period not exceeding 24 hours) in one fasted female rat, a further group of four fasted females was given an oral dose of 2000 mg/kg b.w. (2x 1000 mg/kg b.w. as fractions) of Disperse Red 153, as a formulation in corn oil. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.

Clinical Observations: Transient piloerection, partially closed eyes, decreased activity, ataxia, and slight staining of the ears, paws, and fur were observed. 

Body Weight: All animals showed expected gains in body weight.

Necropsy: The fur of all animals was slightly stained reddish. The large intestines (two animals) and caecum (two animals) were slightly filled with air. White dots were obseverd on the spleen of one animal. The thymus of one animal was slightly enlarged. Two animals showed an accumulation of fatty tissue in the abdomen.

The acute median lethal oral dose (LD₅₀) to rats of Disperse Red 153 was demonstrated to be greater than 2000 mg/kg body weight.