Zircon, cadmium yellow

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg bw (OECD 423; GLP- compliant; female rats)

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:

2021-08-26 to 2021-09-10

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)

Version / remarks:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2020-04-22

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (15-25 ºC, below 70 RH%), protected from light.

Species:

rat

Strain:

Wistar

Remarks:

Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt., H-1122 Budapest, Magyar Jakobinusok tere 4B
- Females nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 189 - 199 g
- Fasting period before study: yes, overnight.
- Housing: animals were housed individually (1st treated animal) or in group (2 animals/cage) in T3H polycarbonate cages; wooden chips: “SAFE 3/4-S-FASERN” certified, (J. Rettenmaier & Söhne GmbH & Co.KG, Rosenberg, Germany); nest material: “Sizzle pet” (LBS (Serving Biotechnology) Ltd., Hookwood, Surrey, United Kingdom).
- Diet (ad libitum): standard laboratory rat diet, SM Rat/Mouse, Breeding & Maintenance, 10 mm, autoclavable (manufacturer: ssniff Spezialdiäten GmbH, Soest, Germany).
- Water (ad libitum): tap water
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 – 23 °C
- Humidity: 39 – 58 %
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12, from 6.00 a.m. to 6.00 p.m.

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

in distilled water (1 % solution)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Justification for choice of vehicle: The selection of the vehicle was made during trial formulations with the test item.
- batch no.: 2005-4320

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
The test item was freshly formulated in the vehicle at the appropriate concentration on the day of administration. The formulations were stirred with magnetic stirrer up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: a starting dose level of 5000 mg/kg bw was selected for the following reasons: the study will be used for EU countries implementing CLP regulation as well as for non-EU countries implementing GHS regulation. Furthermore, the test item is a complex inorganic salt which shows low water solubility. As the bioavailability (and thus solubility) of the test item is a key determinant of toxicity, low toxicity was expected, therefore justifying an initial testing at the limit dose of 5000 mg/kg bw.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: following the end of the dosage, the animals were observed individually once during the first 30 min., at 1, 2, 3, 4 and 6 hours after the treatment and once daily.
Body weight of the animals was recorded on days 0 (prior to dosing), 7 and 14 (prior to necropsy).
- Necropsy of survivors performed: yes, on day 14, all animals were sacrificed, and subjected to a necropsy and a macroscopic examination.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occured.

Clinical signs:

other: All animals were symptom-free during the 14-day observation period at a dose level of 5000 mg/kg bw. Yellow coloured faeces were observed in the bedding on Day 1, which is test item related, but considered as not relevant to human health risk assessment.

Gross pathology:

There were no macroscopic changes seen at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 5000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

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

Acute oral toxicity

One reliable study described in Kiss (2021; OECD 423 (2001); GLP compliant) is considered to be reliable without restrictions and is used as key study for this endpoint. The LD50 was determined to be greater than 5000 mg/kg bw.

 

Justification for classification or non-classification

Acute oral toxicity

The substance is not acutely toxic via the oral route based on an acute oral toxicity test (OECD 423) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

 

Specific target organ toxicant (STOT) - single exposure: oral

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). No classification required.