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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From December 21, 2015 to December 15, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Source: BioLASCO Taiwan Co., Ltd (Taipei, Taiwan)
- Age at study initiation: 8-10 week old
- Housing: one or two animals per cage
- Diet: ad libitum
- Water: ad libitum
- Temperature (°C): 20.2-22.1 °C
- Humidity (%): 41.0-68.4%
- Photoperiod (hrs dark / hrs light): 12-hrs dark / 12-hrs light cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
water for injection
Doses:
Dose Step 1: 2000 mg/kg
Dose Step 2: 2000 mg/kg
No. of animals per sex per dose:
Dose Step 1: three female
Dose Step 2: three female

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

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

In Dose Step 1

No mortality occurred within the first three dayspost-dose. All dose animals tolerated the dose well and survived to termination on Day 15. For one animal (ID No. 0014), pilo-erection was noted for three days post dose and then mild general weakness and abnormally colored mucus membrane (blue) were also noted on Day 1 through Day 3. All study animals were seen to excrete blue colored feces for the first seven days post dose. Two animals (ID No. 0013 and 0014) were also seen to excrete blue colored urine and the signs then persisted through the first three to five days post dose. Blue stained hair over the ano-genital area, forelimbs, forepaws, hindpaws, and/or head was noted on Day 1 through Day 7.

In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. Pilo-erection was noted on two animal (ID No. 0016 and 0018) for two days post dose. All study animals were seen to excrete blue colored feces for the first three days post dose. All animals were also seen to excrete blue colored urine and the signs then persisted on the first three days post dose. Blue stained hair over the ano-genital area, forelimbs, forepaws, hindpaws, and/or head was noted on Day 1 through Day 7. There were no records of animal observations on Day 12 and Day 13.

 

In Dose Step 1 and 2, body weights increased throughout the study period. And gross examination at termination revealed diffused, dark brown discoloration in both kidneys of one animal (ID No. 0014). No other remarkable changes or lesions were noted in the remaining study animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ304 was 5000 mg/kg. Therefore, CJ304 was Category 5 or Unclassified based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315003-GN which is based on the SOP for the OECD 423 (OECD, 2002). A total of 6 female Sprague-Dawley rats were orally dosed with CJ304 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 only remarkable clinical signs observed were pilo-erection, excretion of blue colored urine, and excretion of blue colored and watery feces within the first week post dose. For one animal in Dose Step 1, transient general weakness and abnormally colored mucus membrane (blue) was also observed and gross examination revealed dark brown discoloration of the kidneys. In absence of mortality, moribund state, or other significant clinical signs of toxicity, these results place CJ304 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.