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Description of key information

Acute toxicity: via oral route

The LD50 cut-off value of CJ303 was 5000 mg/kg or Unclassified (OECD TG423).

Acute toxicity: via dermal route

The LD50of CJ303 was greater than 2000 mg/kg B.W. (OECD TG402).

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:
From November 22, 2016 to June 06, 2017
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)
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
- Source: BioLASCO Taiwan Co., Ltd (Taipei, Taiwan)
- Age at study initiation: 9-10 week old
- Housing: one or two animals per cage
- Diet: ad libitum
- Water: ad libitum
- Temperature (°C): 11.4-25.7 °C
- Humidity (%): 30.7-94.4%
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Water for injection (WFI)
Doses:
2000 mg/kg b.w.
No. of animals per sex per dose:
For Dose Step 1: three females
For Dose Step 2: three females
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.

Respectively, the mortalities andclinical observations in Dose Step 1 and 2 as below:

In Dose Step 1

No mortality occurred within the first three days post-dose. All dose animals tolerated the dose well and survived to termination on Day 15.Excretion of feces with deep blue coloration was noted as early as 4 hours post dose and the feces with deep blue discoloration also appeared unformed on Day 1 for one animal (ID No. 0007). Other observations include the deep blue-stained hair in the ano-genital area of one animal on Day 1 (ID No. 0007) was noted. Green or deep blue-stained skin over feet or tail was noted for all of the study animal.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. Excretion of feces with deep blue coloration was noted as early as 4 hours post dose for two out of three animals (ID Nos. 0010 and 0012). The feces with deep blue discoloration also appeared unformed on Day 1 for ID No. 0010. Reports of feces with deep blue discoloration persisted through Day 7 for animals. The excretion of urine of unusual color (green) was also reported for one animal (ID No. 0012) on Day 1 through Day 5. Green or deep blue-stained skin over feet or tail was noted for all of the study animal.

 

In Dose Step 1 and 2, body weights increased throughout the study period. Gross examination at termination revealeddark green discoloration in both kidneys and mesenteric lymph node of all animals in Dose Step 1 and diffuse, dark green discoloration in both kidneys and mesenteric lymph node of all animals in Dose Step 2. No other remarkable changes or lesions were noted in the remaining study animals in either Dose Step 1 or Dose Step 2.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ303 was 5000 mg/kg. Therefore, CJ303 was Category 5 or Unclassified based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65316016-GN which is based on the SOP for the OECD 423 and OECD 423 (OECD, 2002). A total of 6 female Sprague-Dawley rats were orally dosed with CJ303 in two dose steps of three animals each, at 2000 mg/kg b.w. for both Dose Step 1 and Dose Step 2. All animals in the two dose steps tolerated the test article well with increasing body weights and no mortality or moribundity reported. The remarkable clinical signs observed were excretion of deep blue feces in both dose steps and green urine for one animal in Does Step 2. Isolated instances of hair stain in ano-genital area or stained skin over feet or tail were also noted for one animal in Dose Step 1 or in both dose steps. Gross examination revealed dark green discoloration of the kidneys and mesenteric lymph node of all animals, which while resulting in no discernable clinical changes might require follow-up in longer-term toxicology studies with histopathology examination. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ303 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
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
Quality of whole database:
Limited exposure envisaged.

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:
From December 21, 2016 to March 08, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
semiocclusive
Details on dermal exposure:
- Source: Charles River Laboratories, Research Models and Services
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 214-266g
- Housing: Individual caging
- Acclimation period: 5 Days
- Temperature (°C): 19.3-25.2°C
- Relative Humidity (%): 24-49%
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality reported.
Clinical signs:
other: There were no systemic clinical signs noted in any animal throughout the study.
Gross pathology:
There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute dermal median lethal dose (LD50) of the test item CJ303 was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.
Executive summary:

A limit test was carried out at 2000 mg/kg body weight in both sexes (5 rats/sex) of Crl:WI Wistar rats. CJ303 did not cause mortality and no evidence of any gross macroscopic changes in necropsy. There were no systemic clinical signs noted in any animal throughout the study. There were no treatment related effects on body weight or body weight gain during the observation period. Therefore, LD50 of CJ 303 was greater than 2,000 mg/kg B.W.. Based on GHS criteria, CJ303 was Category 5 or Unclassified.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute toxicity: via oral route

A total of 6 female Sprague-Dawley rats were orally dosed with CJ303 in two dose steps of three animals each, at 2000 mg/kg b.w. for both Dose Step 1 and Dose Step 2.All animals in the two dose steps tolerated the test article well with increasing body weights and no mortality or moribundity reported. The clinical signs observed were excretion of deep blue feces in both dose steps and green urine for one animal in Does Step 2. Isolated instances of hair stain in ano-genital area or stained skin over feet or tail were also noted for one animal in Dose Step 1 or in both dose steps. Gross examination revealed dark green discoloration of the kidneys and mesenteric lymph node of all animals, which while resulting in no discernable clinical changes might require follow-up in longer-term toxicology studies with histopathology examination. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ303 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Acute dermal

A limit test was carried out at 2000 mg/kg body weight in both sexes (5 rats/sex) of Crl:WI Wistar rats. CJ303 did not cause mortality and no evidence of any gross macroscopic changes in necropsy. There were no systemic clinical signs noted in any animal throughout the study. There were no treatment related effects on body weight or body weight gain during the observation period. Therefore, LD50 of CJ 303 was greater than 2,000 mg/kg B.W.. Based on GHS criteria, CJ303 was Category 5 or Unclassified.

Justification for classification or non-classification