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Administrative data

Description of key information

Acute toxicity: via oral route

The harmonized LD50 cut-off valueof CJ302 was 5000 mg/kg or Unclassified (OECD TG423).

Acute toxicity: via dermal route

The LD50of CJ302 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 December 21, 2015 to December 01, 2016. Singler dose
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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 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
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
water for injection (WFI)
Doses:
Dose Step 1: 2000 mg/kg
Dose Step 2: 2000 mg/kg
No. of animals per sex per dose:
Dose Step 1: Three females
Dose Step 2: Three females
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. All study animals were seen to excrete orange colored urine on the first five days. Hair loss of the forelimb was noted for one assigned study animal (ID No. 0009) on Day 6 and persistent throughout the remainder of the study period.

 In Dose Step 2

All dose animals tolerated the dose well and survived to termination on Day 15. All study animals were seen to excrete orange colored urine on the first three days. Two animals (ID No. 0010 and 0012) were seen to excrete red colored feces and the signs then persisted through the first seven days post dose. One animal (ID No. 0011)exhibited orange stained hair over the dorsalneck area on Day 1 and Day 2. 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 no remarkable changes or lesions in all dose animals.

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ302 was 5000 mg/kg. Therefore, CJ302 was Category 5 or Unclassified based on GHS criteria.
Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315002-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 CJ302 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, moribundity, or gross findings reported.The only remarkable clinical signs observed were excretion of orange colored urine in both Dose Step and red feces in Dose Step 2. Hair loss was observed at the forelimb of one study animals in Dose Step 1, but they were not likely dose-related. In absence of mortality, moribund state, or other significant clinical signs of toxicity, these results place CJ302 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

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Limited exposure evisaged.

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 January 05, 2017 to April 25, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Laboratories, Research Models and Services
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 223-252g
- Housing: Individual caging
- Acclimation period: 5 Days
- Temperature (°C): 20.1 – 24.9 °C
- Humidity (%):30 – 48%
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Type of coverage:
semiocclusive
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
There were no systemic clinical signs noted in any animal throughout the study. But reddish discoloration by the test item was observed on the treated area on Day 1 and 2 after the application.
Body weight:
One female rat (animal no. 5897) was observed that slight body weight loss between Day 7-14.
Gross pathology:
There was no evidence of any gross macroscopic changes.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
According to OECD 402 test method, the LD50 of CJ302 was greater than 2000 mg/kg body weight. Therefore, CJ302 was Category 5 or Unclassified based on GHS criteria.
Executive summary:

This test using the procedures outlined in the CiToxLAB Study Plan for16/375-002Pand OECD 402 (OECD, 1987). A limit test was carried out at 2000 mg/kg body weight in both sexes (5 rats/sex) of Crl:WI Wistar rats. CJ302 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 302 was greater than 2,000 mg/kg B.W..

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 CJ302 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, moribundity, or gross findings reported.The only remarkable clinical signs observed were excretion of orange colored urine in both Dose Step and red feces in Dose Step 2.Hair loss was observed at the forelimb of one study animals in Dose Step 1, but they were not likely dose-related. In absence of mortality, moribund state, or other significant clinical signs of toxicity, these results place CJ302 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Acute toxicity: via dermal routeA limit test was carried out at 2000 mg/kg body weight in both sexes (5 rats/sex) of Crl:WI Wistar rats. CJ302 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 302 was greater than 2,000 mg/kg B.W.. Based on GHS criteria, CJ302 was Category 5 or Unclassified.

Justification for classification or non-classification