Yttrium chloride hexahydrate

Endpoint summary

Description of key information

Acute oral toxicity

The key acute oral toxicity study (Oroszlány; Klimisch 1) concluded that the LD50 for male and female Wistar rats was equal to or higher than 2000 mg/kg body weight, based on an experiment performed according to the acute toxic class method (OECD guideline 423).

Acute dermal toxicity

Since no reliable data are available for yttrium trichloride, the endpoint is covered using the key acute dermal toxicity study performed with the read across substance yttrium trinitrate (Salvador, 2015; Klimisch 1). This study identified an LD50 value greater than 2000 mg yttrium trinitrate/kg body weight in male and female Sprague-Dawley rats, according to OECD guideline 402. This result is considered relevant for yttrium trichloride too.

Acute inhalation toxicity

Based on Column 2, Annex VIII, section 8.5 adaptation in the REACH regulation, no acute inhalation toxicity study is to be performed as a key study via the oral route and the dermal route of exposure is available.

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:

03 November 2016 - 25 January 2017

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)

Deviations:

no

Remarks:

Minor technical oversights not considered to have impacted the integrity of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Remarks:

Minor technical oversights not considered to have impacted the integrity of the study.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Remarks:

Minor technical oversights not considered to have impacted the integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

No correction for purity was applied during the test.

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI)

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, D-97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adult rats, 11-12 weeks old
- Weight at study initiation: 223 – 242 g. Body weight variation did not exceed +/-20% of the sex mean.
- Fasting period before study: 16 hours maximum, overnight
- Housing: Group caging (3 animals/cage), Type II. polypropylene/polycarbonate, “Lignocel 3/4-S Hygienic Animal Bedding” and “Arbocel crinklets natural” nest building material produced by J. Rettenmaier & Söhne GmbH & Co.KG (D-73494 Rosenberg, Germany) were available to animals during the study.
- Diet (e.g. ad libitum): sniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by Ssniff Spezialdiäten GmbH, D-59494 Soest Germany (278 5652, expiry date: 30 November 2016 and batch number: 141 8884, expiry date: 31 January 2017), ad libitum
- Water (e.g. ad libitum): municipal tap water, ad libitum
- Acclimation period: at least 28 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 – 23.0 ºC
- Humidity (%): 27 - 71%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Trial formulations with the test item.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

Single dose, 2000 mg/kg bw

No. of animals per sex per dose:

6 females. Initially, three female animals were treated with 2000 mg/kg bw of the test item. Only 1 animal was found dead on Day 2, therefore a further 3 animals were treated at the dose level of 2000 mg/kg bw.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
*Clinical observations: 30 minutes, then 1, 2, 3, 4 and 6 hours after the treatment and once each day in the morning for 14 consecutive days. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
*The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes. Macroscopic examination was performed on all animals. The surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed.

Statistics:

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two females were found dead on Day 1 and 2.

Clinical signs:

other: Decreased activity (slight/moderate), hunched back and piloerection were present in both of the found dead animals up to the point of death. The same symptoms were present in all surviving animals from the day of treatment up to Day 7, with brownish colou

Gross pathology:

Found dead animals: In the stomach, diffuse grey/green discoloration of the glandular mucosa, diffuse thickness of the glandular mucosa, clear liquid mixed with digestive contents/diets and dilatation were considered to be test item-related. The changes of the lungs, thymus and urinary bladder were regarded as agonal/post mortem or incidental.
Surviving animals: Red foci of the stomach glandular mucosa seen in 2/4 surviving animals terminated on Day 14, were regarded as test item-related.

Other findings:

None

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item yttrium trichloride hexahydrate was found to be equal to or above 2000 mg/kg bw in female Crl:WI Wistar rats.
According to the GHS criteria, classification of yttrium trichloride hexahydrate in "Category 5" for acute oral toxicity is appropriate. Under the CLP Regulation, no classification is required.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

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:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2015-07-01 to 2015-10-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 5 male and 5 female (nulliparous and non-pregnant) rats, Hsd: Sprague Dawley SD; from Harlan Italy s.r.l. San Pietro al Natisone (UD), Italy
- Age at order: 6 to 8 weeks
- Weight at arrival: 173-183 grams
- Fasting period before study: no data
- Housing: Up to 5 animals of one sex per cage during acclimatisation, individually caged during the study; polysulphone solid bottomed cages measuring 59.5x38x20 cm during acclimatisation period and 42.5x26.6x18.5 cm during the study with nesting material provided into suitable bedding bags; daily inspected and changed as necessary (at least 3 times/week).
- Diet (e.g. ad libitum): ad libitum, 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
- Water (e.g. ad libitum): ad libitum, drinking water supplied to each cage via a water bottle
- Acclimation period: at least 5 days, veterinary health check during acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 55 % +/- 15%
- Air changes (per hr): approximately 15-20 per hour
- Photoperiod (hrs dark / hrs light): daily light/dark cycle of 12/12 hours, artificial lighting (fluorescent tubes)

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surfaces of the trunk of each animal, clipped free of hair on the day before dosing
- % coverage: approximately 10% of the body surface
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a lenght of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): no data
- Constant volume or concentration used: yes
- On the day of dosing, aliquots of the test item to be administered were weighed according to the body weight of each animal measured prior to dosing.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
*mortality and morbidity: throughout the study, all animals were checked twice daily
*clinical signs: Day of dosing: Session 1: on dosing; Session 2: approximately 1 hour after dosing; Session 3: approximately 2 hours after dosing; Session 4: approximately 4 hours after dosing. Daily thereafter for a total of 14 days (Session 1).
*body weight: All animals were weighed at allocation to the study, on the day of dosing (day 1) and on days 8 and 15. Body weight change calculated for days 8 and 15 of the dosing phase was relevant to day 1 of the phase.
- Necropsy of survivors performed: Yes, all animals were sacrificed on day 15 by carbon dioxide narcosis.
- Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site). All abnormalities were recorded.

Statistics:

No data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical signs were limited to scabs on the dorsal/thoracic region observed in male and female animals from day 5 up to day 13/14 of the observation period. In addition, desquamation of the dorsal region was observed in three females on day 7 and in one f

Gross pathology:

No abnormalities were found at the external examination performed in all animals at the end of the study, with the exception of multiple scabs observed on the treatment site of one female (animal no. A1463003). No internal abnormalities were found in any treated animal.

Interpretation of results:

not classified

Conclusions:

The results indicated that the test item, yttrium trinitrate, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg (corrected for water content, 28.7%). The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg. European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would suggest that the substance is not to be classified.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

Because no reliable information has been identified on the acute dermal toxicity of yttrium trichloride, the endpoint was covered using a reliable acute dermal toxicity study performed with the read across substance yttrium trinitrate (Salvador, 2015), an yttrium compound with similar water solubility as yttrium trichloride. The read across justification document is attached to IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

yttrium trinitrate anhydrous

Remarks on result:

other: Based on the read across approach, this result obtained with yttrium trinitrate is considered relevant for yttrium trichloride as well.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute toxicity: oral

A single study on the acute oral toxicity of yttrium trichloride was identified (Oroszlány, 2017). In this study, two groups of 3 female rats were exposed to a single dose of 2000 mg/kg bw of yttrium trichloride hexahydrate. In the first group, one animal was found dead on Day 2 after treatment, and in the second group, one animal was found dead on Day 1 after treatment. Decreased activity (slight/moderate), hunched back and piloerection were present in both of the found dead animals up to the point of death. The same symptoms were present in all surviving animals from the day of treatment up to Day 7. Body weight loss in 3 of the 4 surviving animals during the first week of the study indicated a test item-related effect. In the stomach of found dead animals, diffuse grey/green discoloration of the glandular mucosa, diffuse thickness of the glandular mucosa, clear liquid mixed with digestive contents/diets and dilatation were observed and considered to be test item-related. In surviving animals, red foci in the stomach glandular mucosa was seen in 2 of the 4 surviving animals terminated on Day 14. This observation was regarded as test item-related. Based on the results of this study, the LD50 was considered to be equal to or higher than 2000 mg/kg bw. Classification for Acute Toxicity Cat. 5 is appropriate under the GHS, however, under the CLP Regulation no classification is required. Altogether, the observed effects are considered to be related to the irritating effect of the test item in the stomach (local effects). The study was considered reliable without restriction (Klimisch 1) and was assigned key status for endpoint coverage.

Acute toxicity: inhalation

Based on column 2, Annex VIII, section 8.5 adaptation in the REACH regulation, no acute inhalation toxicity study is to be performed as a key study via the oral route and the dermal route of exposure is available.

Acute toxicity: dermal

No reliable data have been identified on the acute dermal toxicity of yttrium trichloride. Therefore, the endpoint is covered using a study performed with the read across substance yttrium trinitrate, i.e. an yttrium compound with similar water solubility as yttrium trichloride. In this study, Salvador (2015) studied the acute dermal toxicity of yttrium trinitrate in 5 Sprague-Dawley rats per sex (OECD guideline 402). The dose level tested was 2000 mg yttrium trinitrate/kg bw. After 15 days of observation the dermal LD50 was concluded to be > 2000 mg/kg bw. No mortality occurred.

Clinical signs were limited to scabs on the dorsal/thoracic region observed in male and female animals from day 5 up to day 13/14 of the observation period. In addition, desquamation of the dorsal region was observed in three females on day 7 and in one female only from day 9 to the end of the study.

Body weights and body weight changes were within the expected range for this species and age of animals at the end of the study.

No abnormalities were found at the external examination performed in all animals at the end of the study, with the exception of multiple scabs observed on the treatment site of one female (animal no. A1463003). No internal abnormalities were found in any treated animal.

The results of this study are considered relevant for yttrium trichloride as well. This study is assigned key status for endpoint coverage. The read across justification document is attached to IUCLID Section 13.

Justification for classification or non-classification

Based on the results of the key acute oral toxicity study and according to the criteria of the CLP Regulation, yttrium trichloride should not be classified as acute oral toxicant.

Based on the results of the key acute dermal toxicity study performed with the read across substance yttrium trinitrate, yttrium trichloride is not to be classified as acute dermal toxicant according to the CLP Regulation.

No data available to conclude on classification for acute inhalation toxicity.