CJ309

Endpoint summary

Description of key information

Acute toxicity: via oral route

The harmonized LD50cut-off valueof CJ309 was 5000 mg/kg or Unclassified (OECD TG423).

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 15, 2016

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: 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 female
Dose Step 2: three female

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Clinical signs:

other:

Respectively, the mortalities and clinical 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 the first three days post dose, pilo-erection was noted for one animal (ID No. 0026) and mild decreased activity was noted for one animal (ID No. 0025). Abnormally colored mucus membrane (blue) was also noted for all three study animals on Day 1 through Day 8 and the signs for two animals (ID No. 0026 and 0027) persisted to Day 12. All study animals were seen to excrete blue colored feces for the first three days post dose. For two animals (ID No. 0025 and 0027), the blue colored feces had watery consistency with the first two to three days post dose. Two study animals (ID No. 0026 and 0027) were seen to excrete blue colored urine and the signs then persisted through the first three days. For all animals,blue stained hair over the ano-genital area, forepaws, hindpaws, and/or muzzle was noted in the first two or three days post dose. Butfor one animals(ID No. 0025), blue stained hair over the ano-genital area was noted from Day 1 through Day 12.

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 blue colored feces for the first three days post dose and then one animal (ID No. 0030) persisted to seven days post dose. For two animals (ID No. 0028 and 0029), the blue colored feces had watery consistency with the first two to three days post dose.One animal (ID No. 0028) was also seen to have red stained hair at the nose in the first two days post dose and excretion of soft brown feces half an hour post dose. All study animals were seen to excrete blue colored urine. The signs for two animals (ID No. 0028 and 0029) and one animals (ID No. 0030) persisted through the first three days and seven days,respectively. For all animals,blue stained hair over the ano-genital area, forepaws, hindpaws, and/or muzzle was noted in the first two or three days post dose. 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 diffuse, dark brown discoloration in both kidneys of all study animals.

 

Interpretation of results:

GHS criteria not met

Conclusions:

According to OECD 423 test method a, the harmonized LD50 cut-off value of CJ309 was 5000 mg/kg. Therefore, CJ309 was Category 5 or Unclassified based on GHS criteria.

Executive summary:

This test using the procedures outlined in the QPS Taiwan Study Plan for T65315005-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 CJ309 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 excretion of blue urine and feces within the first three to seven days post dose. Transient pilo-erection, decreased activity, and abnormally colored mucus membrane (blue) was also observed for some animals in either dose step. On the other hand, gross examination revealed dark brown discoloration of the kidneys of all study animals in both dose steps, suggestive of possible test article effect on the kidney at 2000 mg/kg b.w. or higher. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ309 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 evisaged.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

The approach taken is to consider the chemical structure and class of this substance then estimate the endpoints from both the chemistry, including read-across to similar substance types through literature searches and basic QSAR modelling. The result is considered validated.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Methods not always explicit in reviews, but OECD testing principles appear to have been followed in most cases.

GLP compliance:

not specified

Test type:

other: Review of various studies

Limit test:

no

Species:

rat

Sex:

male/female

Details on test animals or test system and environmental conditions:

Mostly rat data, but dermal effects on guinea pigs and rabbits also examined (non-maximised sensitisation studies and dermal irritation)

Type of coverage:

not specified

Vehicle:

not specified

Doses:

Up to 2000 mg/kg

Control animals:

not specified

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality reported

Clinical signs:

other: Other than discolouration, no clinical signs

Gross pathology:

No adverse systemic effects reported.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on reliable review of literature and assessment of similar sulphonated azo dyes.
No further animal testing is justified.

Executive summary:

From assessment of similar sulphonated azo dyes, none are noted as being acutely toxic and there is no evidence of dermal absorption. From various data sources, it is considered unlikely that the substance will be acutely toxic by the dermal route. Most azo dyes have acute toxicity discriminating dose > 2000 mg/kg and the similar substances reviewed fall into this category.

 

The impact of lithium is not likely to impact on the toxicity when comparing with sodium salts as dermal toxicity of lithium substances are reported to be low and in view of the minimal % w/w content of lithium, this is not significant in the classification of toxicity.

 

Studies on guinea pigs and rabbits for sensitising and irritancy assessment have not revealed any evidence of adverse systemic effects. Only the maximised sensitising studies (ie injected) appear to give positive results, confirming low levels of dermal absorption. Discolouration of skin will occur and the colour is difficult to wash off.

 

It is not considered justifiable to perform further acute dermal toxicity testing on CJ309 in view of the similarity with other dyes assessed in this report. It should also be noted that some other registrations have indicated waivers for this endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

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 CJ309 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 excretion of blue urine and feces within the first three to seven days post dose.Transient pilo-erection, decreased activity, and abnormally colored mucus membrane (blue) was also observed for some animals in either dose step.On the other hand, gross examination revealed dark brown discoloration of the kidneys of all study animals in both dose steps, suggestive of possible test article effect on the kidney at 2000 mg/kg b.w. or higher. In absence of mortality, moribund state, or other significant clinical and gross signs of toxicity, these results place CJ309 in the GHS Category 5 or Unclassified, with harmonized LD50 cut-off value at 5,000 mg/kg or Unclassified.

Justification for selection of acute toxicity – dermal endpoint

Reliable assessment based on similar substances.

Justification for selection of acute toxicity – dermal endpoint
The LD50 of the read-across substance was 2000 mg/kg/bw.

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