Bismuth chloride oxide

Endpoint summary

Description of key information

Acute toxicity, oral (similar to OECD 401): LD50 > 10000 mg/kg bw (50% test substance in water)

Acute toxicity, oral (similar to OECD 401): LD50 > 10000 mg/kg bw (70% test substance in castor oil)

Acute toxicity, inhalation (OECD 436): LC50 > 5.07 mg/L air

RA from source substance Bismuth trioxide (CAS 1304-76-3)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Higher doses tested. No tables with individual data included.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

The test substance was diluted to a formulation of 50% in water.

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Females nulliparous and non-pregnant: Yes
- Weight at study initiation: 190 to 236 g (males); 190 to 225 g (females)
- Fasting period before study: Yes, over night prior dosing

Route of administration:

oral: gavage

Vehicle:

water

Doses:

1000, 1590, 2510, 3980, 6310, 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and clinical signs at one, four, and 24 hours and once daily thereafter for a total of 14 days.
- Necropsy of survivors performed: Yes, on all animals which died during the study and on those sacrificed (chloroform overdose) at termination

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

10 000 mg/kg bw

Based on:

test mat.

Mortality:

1590 mg/kg bw: One male died on day 8
10000 mg/kg bw: One female appeared depressed and hunched at 24 hours, and subsequently died

Clinical signs:

other: 1000 mg/kg bw: One male showed wheezing from day 5 to termination

Gross pathology:

The male rat that died during the study (1590 mg/kg bw) demonstrated dark red areas on all lobes of the lungs. The death of one female rat during the study (10,000 mg/kg bw) was attributed to accidental puncture during gastric intubation.

In the guideline comparable but non-GLP compliant acute oral toxicity test, the test substance was tested for acute oral toxicity with the following doses 1000, 1590, 2510, 3980, 6310 and 10000 mg/kg bw for male and female rats. For each dose and sex 5 animals were used. The test substance (a fomulation of 50%) was administrated undiluted. The animals were observed for a period of 14 days. One male rat died at the 1590 mg/kg level and one female rat died at the 10000 mg/kg level. The death at the higher dose was attributed to accidental puncture during gastric intubation.

In the present acute oral toxicity study an LD50 cut-off value of > 10000 mg/kg bw was found.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Higher doses tested. No tables with individual data included

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Two compounds (Biju BO and Biju MO) both a formulation of 70% CAS 7787-59-9 in castor oil were tested.
Appearance: Both are silvery white pastes with a faint unpleasant odor

Species:

rat

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Females nulliparous and non-pregnant: Yes
- Weight at study initiation: 150 to 230 g (males); 150 to 222 g (females)
- Fasting period before study: Yes, over night prior to dosing

Route of administration:

oral: gavage

Vehicle:

castor oil

Doses:

Test 1: 130, 279, 610, 1300, 2810, 10000 mg/kg bw
Test 2: 93, 200, 430, 930, 2020, 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (mortality and clinical signs) and weighing: At one, four, and 24 hours and once daily thereafter for a total of 14 days.
- Necropsy of survivors performed: Yes, on all animals which died during the study and on those sacrificed (chloroform overdose) at termination

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Result refers to both tested compounds

Mortality:

Both compounds test 1 and test 2: All male and female animals survived to day 14.

Clinical signs:

other: Compound 1: At 2810 mg /kg bw, day 2: Female rats produced soft feces At 10000 mg/ kg bw, from one hour through day 3: Male and female rats exhibited rough oily fur and soft feces At 10000 mg/ kg bw, from four hours through day 2: Slight to moderate dep

Gross pathology:

At terminal necropsy animals receiving either compound exhibited a yellow colored fluid in the intestinal tract (males and females) at the 10000 mg/kg bw level.

In the guideline comparable but non-GLP compliant study for acute oral toxicity two compounds of the test substance as 70% formulation were tested.

The test substance was tested in five male and five female albino rats at graded dosage levels of 93 mg/kg bw – 10000 mg/kg bw.

Toxic signs included soft feces, rough oily fur, and depression, which generally persisted through day 5 at the highest level in both sexes. Both sexes at necropsy on day 14 exhibited a yellow colored fluid in the intestinal tract at the 10000 mg/kg bw level. All male and female rats survived to day 14. The LD50 for acute oral toxicity was determined to be greater than 10000 mg/kg bw for male and female rats.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises two adequate and reliable studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 - 26 July 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

07 Sept 2009

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Amt für Arbeitsschutz, Arbeitnehmerschutz Hamburg (2009-11-12)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: CD / Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany
- Age at study initiation: 50 days (males), 64 days (females)
- Weight at study initiation: 229-242 g (males) and 236-240 g (females)
- Fasting period before study: Feeding was discontinued approx. 16 hours before exposure.
- Housing: During the 14-day observation period the animals are kept by sex in groups of 2 - 3 animals in MAKROLON cages (type III plus).
- Diet: Commercial diet, ssniff® R/M-H V1534 served as food.
- Water: ad libitum, tap water
- Acclimation period: At least 5 adaptation days and animals were acclimatised to the test apparatus for approx. 1 hour on 2 days prior to testing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 15
- Photoperiod: 12 hours dark/light cycle

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.7 µm

Geometric standard deviation (GSD):

2.95

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The study was carried out using a dynamic inhalation apparatus (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & EBEN. The apparatus consists of a cylindrical exposure chamber which holds the animals in pyrex tubes at the edge of the chamber in a radial position.
- Exposure chamber volume: 40 L
- Source and rate of air: Air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter. At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h, 22.5 air changes per hour).
- System of generating particulates/aerosols: The dust of the test material was generated with a rotating brush dust generator. The generator was fed with compressed air (5.0 bar) from a compressor.
- Treatment of exhaust air: The exhaust air was drawn through gas wash-bottles.
- Temperature, humidity, pressure in air chamber: Temperature (26.5°C ± 0.8°C) and humidity (69.2% ± 1.4%) were measured once every hour with a climate control monitor.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter and pump, controlled by a rotameter. Dust samples were taken once every hour during the exposure.
- Samples taken from breathing zone: yes; a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg).

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: An analysis of the particulate size distribution was carried out twice during the exposure period using a cascade impactor. The dust from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance. Delta of slides’ weight were determined.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis to be 2.700µm. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.95 from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis. In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particulate size with a Malvern Sizer by Malvern, 71083 Herrenberg, Germany.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: according to guideline

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

Duration of exposure:

4 h

Concentrations:

5.00 mg/L air (nominal concentration)
5.07 mg/L air (measured concentration)

No. of animals per sex per dose:

3 males and 3 females / dose; only one concetration tested (limit test)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Careful clinical examinations were made at least twice daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily (in the morning starting on test day 2) to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals. Individual weights of animals were determined once during the acclimatisation period, before and after the exposure on test day 1, on test days 3, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.
- Necropsy of survivors performed: yes
- Other examinations performed: Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremor, convulsions, salivation diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea, rhinitis etc.
Necropsy of all animals was carried out and all gross pathological changes were recorded. No microscopic examination was carried out as no pathological findings were noted at necropsy.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.07 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: Under the present test conditions, a 4-hour inhalation exposure to dibismuth trioxide at a concentration of 5.07 mg/L air revealed slight ataxia and slight dyspnoea in 2 or 3 male and 3 female rats.

Body weight:

All animals gained the expected body weight throughout the study period.

Gross pathology:

No findings.

Other findings:

No other findings were observed.

Summary

The aim of the present experiment was to obtain information on the acute toxicity and respiratory irritation, following a single 4-hour inhalation exposure of rats to dibismuth trioxide.

Rats were exposed to a dry aerosol of dibismuth trioxide at a gravimetricly determined concentration of 5.07±0.09 mg dibismuth trioxide/L air for 4 hours by inhalation using a dynamic nose-only exposure chamber. The aerosol was generated with the aid of a dry, rotating brush dust generator.

In the inhalation chamber, close to the animals' noses, the generated aerosol particulates had a mass median aerodynamic diameter (MMAD) of 2.700 µm as determined with a cascade impactor. The Geometric Standard Deviation (GSD) of the MMAD was calculated as 2.95. No smaller MMAD could be obtained with the test item supplied.

Under the present test conditions, a 4 -hour inhalation exposure to dibismuth trioxide at a concentration of 5.07 mg/L air (determined by gravimetric analysis) caused no mortality, and the body weight changes of all animals revealed throughout the study period normal gains.

A 4 -hour inhalation exposure to dibismuth trioxide at a concentration of 5.07 mg/L air revealed slight ataxia and slight dyspnoea on test day 1 immediately after end of exposure until 3 hours post exposure in 2 or 3 male and 3 female animals.

Under the conditions of this study, the 4 -hour inhalation LC₅₀of dibismuth trioxide is >5.07 mg/L air, and hence, the LC₅₀cut-off value unclassified.

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information represents an adequate, reliable (Klimisch score 1) study from a reference substance with similar intrinsic properties. Read-across is justified based on common characteristic chemical properties. The information is consistent and provides sufficient evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No. 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity

Justification for read-across

There are data available regarding acute oral toxicity for bismuth chloride oxide (CAS 7787-59-9).

 

As there is no data available regardingacute inhalation toxicity for Bismuth chloride oxide (CAS 7787-59-9), read-across from an appropriate structural analogue substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

For acute inhalation toxicity information from the analogue substance bismuth trioxide (CAS 1304-76-3) will be taken into account to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

 

Acute oral toxicity

CAS 7787-59-9

An acute oral toxicity study was performed with the test material (50% formulation in water) similar to OECD guideline 401 (reference 7.2.1-1). Groups of 5 fasted male and female rats received oral gavage doses of 1000, 1590, 2510, 3980, 6310 and 10000 mg/kg bw. The animals were observed for 14 days after administration. One male died on day 8 at 1590 mg/kg bw. One female appeared depressed and hunched on day 1 (24 h) at 10000mg/kg bw and subsequently died. One male showed wheezing from day 5 to termination. Necropsy revealed that the dead male rat demonstrated dark red areas on all lobes of the lungs. The death of the female rat during the study was attributed to accidental puncture during gastric intubation. The rest of the animals showed no abnormal gross findings in the examined organs and tissues. The acute oral LD50 was found to be greater than 10000 mg/kg bw.

 

Another study was performed with two compounds (1: Biju BO and 2: Biju MO) of the test material (both 70% formulations in castor oil) similar to OECD guideline 401 (reference 7.2.1-2). Groups of 5 male and female fasted albino rats received oral gavage doses of 130, 279, 610, 1300, 2810, 10000 mg/kg bw and 93, 200, 430, 930, 2020, 10000mg/kg bw of compound 1 and 2, respectively. The animals were observed for 14 days after administration. No mortalities were observed. On day 2 after receipt of compound 1, one female produced soft faeces at 2810 mg/kg bw. At 10000 mg/kg bw all male and female rats exhibited rough oily fur and soft faeces from 1 h until end of day 3 and slight to moderate depression from 1 h until end of day 2. After receipt of 10000 mg/kg bw of compound 2, male and female rats exhibited rough oily fur and soft faeces after 1 h and moderate depression was observed after 24 h. All clinical signs completely disappeared by day 5. Necropsy revealed that all rats demonstrated yellow coloured fluid in the intestinal tract (males and females) at the 10000 mg/kg level (with both compounds). The acute oral LD50 was found to be greater than 10000 mg/kg bw.

 

Supportive information is available based on an acute oral toxicity study, performed with the test material, similar to OECD guideline 401 (reference 7.2.1-3). Groups of 5 fasted male and female Sprague-Dawley Caesarean-derived rats received oral gavage doses of 464, 1000, 2150, 4640, 10000, 21500 mg/kg bw. The animals were observed for 14 days after administration. No mortalities, clinical signs or abnormal gross findings in the examined organs and tissues were observed. The acute oral LD50 was found to be greater than 21500 mg/kg bw.

 

Another supporting acute oral toxicity study was performed with the test material similar to OECD guideline 401 (reference 7.2.1-4). Groups of 10 or 25 Holtzman rats received oral gavage doses of1250, 2500 or 5000 mg/kg bw, respectively. The animals were observed for 7 days after administration. No mortalities or clinical signs were observed during the observation period. The acute oral LD50 was found to be greater than 5000 mg/kg bw.

 

Another supporting acute oral toxicity study was performed with the test material similar to OECD guideline 401 (reference 7.2.1-5). Groups of 5 or 20 CF-1 (Carworth) mice received oral gavage doses of 10000 and 20000 and 37500 mg/kg bw, respectively. The animals were observed for 5 days after administration. No mortalities or clinical signs were observed during the observation period. The acute oral LD50 was found to be greater than 37500 mg/kg bw.

 

Acute inhalation toxicity

CAS 1304-76-3

Toxicity via inhalation of the test material was tested in a study performed according to OECD guideline 436 and GLP (reference 7.2.2-1). Three male and female CD/Crl:CD(SD) rats were nose-only exposed to an aerosol of an analytical concentration of 5.07 mg/L for 4 h. Apart from slight ataxia and slight dyspnoea on test day 1 immediately after the end of exposure until 3 hours post exposure in 2 or 3 male and 3 female animals, no further signs of toxicity and no mortality were observed until the end of the 14 day observation period. Thus, the LC50 was considered to be >5.07 mg/L.

Justification for classification or non-classification

The available data on acute toxicity following the oral route do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.

The available data on acute toxicity following the inhalation route after application of the analogue substance Bismuth trioxide(CAS 1304-76-3) do not meet the criteria for classification according to Regulation (EC) 1272/2008.

Therefore, Bismuth chloride oxide (CAS 7787-59-9) is also considered to not have toxic properties following inhalation.