[No public or meaningful name is available]

Endpoint summary

Description of key information

Acute oral toxicity: LD50 for acute oral toxicity was set greater than 5000 mg/kg bw

Acute inhalation toxicity: LC50 (rats; 4 hours) > 5.06 mg/L air (actual concentration) (OECD 436; GLP; male and female rats; 4 hr exposure)

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:

2017-12-12 to 2017-12-27

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 2017-05-08

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: at +10°C to +25°C, stored in a tightly closed original container in a dry place.

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 53-54 days
- Weight at study initiation: 192 - 204 g
- Fasting period before study: feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
- Housing: groups of 3 animals in MAKROLON cages (type III plus); bedding material: granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany)
- Diet (ad libitum, for exception refer to "fasting period before study" above): commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 °C ± 3 °C (maximum range)
- Relative humidity: 55% ± 10% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 0.8 % aqueous hydroxypropylmethylcellulose

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: the vehicle was chosen, since it is known not to produce toxic effects.
- Batch no.: 16H 23-B02-333146
- Source: Fagron GmbH & Co., 22885 Barsbüttel, Germany

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

DOSAGE PREPARATION:
The test item was suspended in the vehicle.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed before and immediately, 5, 15, 30 and 60 minutes, as well as 3, 6 and 24 hours after administration. During the follow-up period of two weeks, clinical signs were observed at least once a day until all symptoms subsided, thereafter each working day.
Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes, at the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically.

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No animal died prematurely.

Clinical signs:

other: other: The administration of the test item did not reveal any signs of toxicity.

Body weight:

other body weight observations

Gross pathology:

No pathological changes were observed 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

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

one key study available

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The two spinel type pigments are structurally very similar with similar composition. Both show a very low solubility in different artificial and aqueous media. In order to compare the potential hazard of the target substance with the source substance, a dustiness test with subsequent MPPD modelling was conducted. Based on the results of the MPPD model about 0.6 % or less of inhaled material is predicted to be deposited in the pulmonary region (PU), whereas the material deposited in the tracheobronchial (TB) and the extrathoratic region (Head) may be assumed to be cleared to the GI tract (i. e., by mucociliary escalation and subsequent swallowing). When comparing this with the outcome of the acute inhalation toxicity study, showing no toxicity up to the limit concentration at an estimated PU deposition of 9.0%, one can safely exclude any acute inhalation toxicity for the target substance.
Based on the information summarised above an analogue approach for read-across of the endpoint “Acute inhalation toxicity ” from the structural analogue to the target substance is considered justified (see also attached document under in section 13 of this technical dossier).

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.06 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No animal died prematurely.

Clinical signs:

other: see other findings below

Body weight:

One female animal of the main study appeared to be reduced in body weight gain at the end of the study.

Gross pathology:

Dark discoloured lungs were observed in all animals of the main study (14-day sacrifice).

Other findings:

Under the present test conditions, a 4-hour inhalation exposure to the test item at a concentration of 5.06 mg/L air revealed slight ataxia and slight dyspnoea (reduced frequency of respiration with increased volume) until 60 minutes or 3 hours post exposure in all 3 of 3 male and 3 of 3 female animals, respectively. However, this effect is considered to be an overall clinical sign of general toxicity common to dust exposure, but not necessarily test item-related.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (rats; 4 hours) > 5.06 mg/L air (actual concentration)
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
Furthermore, no signs of respiratory tract irritation were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

One acute oral toxicity study with chromium, iron, titanium and zinc spinel and rutile is available, which is a GLP study conducted according to OECD guideline 423. The acute oral toxicity was tested by performing a limit test in female Crl:CD (SD) rats. Three rats received a single oral gavage at a dose of 5000 mg/kg bw. All animals were observed daily for a period of 14 days. Individual body weights were recorded before administration and thereafter in weekly intervals. At the end of the study all animals were sacrificed, dissected and inspected macroscopically. No mortality, clinical signs, changes in body weight or pathological changes were observed. The LD50 for acute oral toxicity was set greater than 5000 mg/kg bw.

Acute inhalation toxicity

One reliable study described in Haferkorn (2017; OECD 436 (2009); GLP) is considered to be reliable without restrictions and is used as key study for this endpoint. The LC50 was determined to be greater than 5.06 mg/L air (actual concentration).

Justification for classification or non-classification

Acute oral toxicity:

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the oral route. Thus, according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.

Acute inhalation toxicity

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the inhalation route. Thus, according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.

Specific target organ toxicant (STOT) – single exposure: inhalation

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute inhalation toxicity test (OECD 436).Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, inhalation are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.