Barium carbonate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 = 1690 mg/kg bw
Acute dermal toxicity: derogation statement included; according to SIAR 2008 an LD50 >1895 mg/kg was stated in the NIAR report 2008 (based on barium carbonate)
Acute inhalation toxicity: data waiving

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:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-compliant guideline study with the following deviations: - According to the guideline, healthy young adults should be used. The age of the rats was missing in this report. - The analytical purity of the test substance is not indicated in the report.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(Adopted: 12 May 1981)

Deviations:

yes

Remarks:

(see rational for reliability)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. A. Ivanovas, 7964 Kisslegg/Allgäu
- Age at study initiation: Not reported
- Weight at study initiation: Males: 100-125 g; Females: 100-115 g
- Housing: Group housing of five animals per sex per cage in labelled Makrolon cages (type III) containing sawdust bedding material (Fa. Brandenburg, 2849 Goldenstedt-Arkeburg).
- Diet (ad libitum except overnight prior to and approx. 4 hours after dosing): Pelleted rodent diet (Ssniff R10 pellets, Ssniff Versuchstierdiäten, 4770 Soest/Westf.
- Water (ad libitum): Tap water
- Acclimation period: 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
Animals were housed in a controlled environment.
- Temperature: ca. 20°C
- Relative humidity: 40 - 60 %
- Air changes: Approx. 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1%
- pH value of suspensions: 10

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg
The control animals received the vehicle alone.

Doses:

1470 mg/kg, 1780 mg/kg, 2150 mg/kg

No. of animals per sex per dose:

5 male / 5 female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: On the day of dosing animals were observed for signs of reaction to treatment at frequent intervals. On subsequent days animals were observed at leaste once daily. Individual bodyweights were recorded on the day of dosing and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The acute oral median lethal dose (LD50) based on the mortality rate (x/n) during 14 days after dosing was calculated using the method of Finney (1971), Probit Analysis (3rd Edition) Cambridge University Press.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 690 mg/kg bw

95% CL:

1 060 - 2 010

Mortality:

Mortalities occured within 72 hours after dosing.

Number of dead males per dose:
Control: 0/5
1470 mg/kg: 2/5
1780 mg/kg: 4/5
2150 mg/kg: 4/5

Number of dead females per dose:
Control: 0/5
1470 mg/kg: 1/5
1780 mg/kg: 2/5
2150 mg/kg: 4/5

Clinical signs:

other: Slight pilo-erection was observed in the control animals on the day of dosing. Clinical signs observed on the day of dosing in rats treated with bariumcarbonate included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), incr

Gross pathology:

Autopsy mainly revealed congestion of liver and and inflammation of the glandular region of the stomach in rats that died during the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the results of this study, an LD50 of 1690 mg/kg bw has been calculated for males and females for BaCO3.

Executive summary:

In a GLP compliant acute oral toxicity study, performed according to OECD guideline 401, the test item BaCO3 was administered to groups of 5 male and 5 female Sprague Dawley rats at dose levels of 1470, 1780 and 2150 mg/kg body weight.

Mortalities occurred within 72 hours after dosing. Signs of reaction to treatment included pilo-erection, hunched posture, pallor of extremities, abnormal gait (waddling), increased or decreased respiratory rate, laboured respiration, diarrhoea, chromodakryorrhoea, decreased motility and loss of righting reflex. Complete recovery was evident in surviving animals by day 3 as judged by external appearance and behaviour.

Autopsy mainly revealed congestion of liver and inflammation of the glandular region of the stomach in rats that died during the study.

Body weight gain was poor in the surviving male rat of the highest dose group (2150 mg/kg) and one female rat of the mid-dose group (1780 mg/kg).

In conclusion, the LD50 of BaCO3 is calculated to be 1690 mg/kg body weight by oral route in the rat.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 690 mg/kg bw

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 toxicity, oral:

A reliable acute oral toxicity study with BaCO3 (Müller, 1983) results in an LD50 of 1690 mg/kg for males and females. Based on the results of this study, it was concluded that BaCO3 requires a classification and labelling as "acute tox 4"; H302 (harmful if swallowed) according to GHS.

Acute toxicity, dermal:

The toxicity of barium carbonate and barium chloride may reasonably be considered to be determined by availability of Ba²⁺cations. As a first surrogate for bioavailability, the water solubility of a test substance may be used. Barium carbonate is poorly soluble in water whereas barium chloride is well water soluble.Read-across from soluble to the poorly soluble barium compound is considered acceptable because toxicokinetic data on the poorly soluble barium carbonate indicates a markedly lesser bioavailability than the soluble barium chloride. However, it is to be concluded that this read-across will likely lead to rather conservative no-effect levels.

Annex VIII, point 8.5 of Regulation No 1907/2006 specifies that information on the acute toxicity of substances shall be provided according to the relevant exposure routes. According to point 8.5.3, column 2, testing by the dermal route is appropriate if (1) inhalation of the substance is unlikely, and (2) skin contact in production and/or use is likely, and physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. For barium carbonate, inhalation can be anticipated. Therefore, provision (1) of point 8.5.3 is not fulfilled. However, according to the SIAR, an acute dermal toxicity study on barium chloride was conducted under OECD TG 402 in compliance with GLP: in this study, the dermal LD₅₀was greater than 2000 mg/kg bw in rats. Nevertheless, the primary source for this study is not available: the SIAR refers to a NIER report dated 2008.

Acute toxicity, inhalation:

A pre-test was performed to develop a design for generating a stable testing atmosphere. However, based on the technical properties of barium carbonate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound. Due to (i) the particle size which is much larger than the pestled substance used for the pre-study, (ii) the low mobility and (iii) the negligible volatility of barium carbonate, the test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application.

Justification for classification or non-classification

Acute oral toxicity

In a reliable GLP study performed to OECD Guideline 401 (Müller, 1983), barium carbonate was administered by gavage at 1470, 1780 and 2150 mg/kg bw to 5 male and 5 female rats (Sprague-Dawley). The animals were observed for clinical signs and mortality for 14 days. male The study results in an LD50 of 1690 mg/kg bw and therefore it was concluded that BaCO3 requires a classification and labelling as "acute tox 4"; H302 (harmful if swallowed) according to GHS. The classification as 'harmful' is supported by read-across with BaCl2

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 of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 mg/kg bw in addition to this effects which were responsible for the death of the animals. No classification required.

 

Acute dermal toxicity

According to the SIAR 27 prepared for barium chloride, an acute dermal toxicity study on barium chloride was conducted according to OECD TG 402, in compliance with GLP. In this study, the dermal LD50 was greater than 2000 mg BaCl₂/kg bw in rats. It is note here that the primary data could not be made available to the registrant but using the secondary information no classification according to regulation (EC) 1272/2008 will be necessary for barium carbonate (LD₅₀ >1895 mg/kg bw.). For argumentation on read across please refer to the discussion above.

Acute inhalation toxicity

Based on the technical properties of barium carbonate, the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound. Due to the MMAD/GSD and the particle size which are much higher than the pestled substance used for the pre-study, the low mobility and the negligible volatility of barium carbonate, the test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application. No classification is required according to regulation (EC) 1272/2008.

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

The classification criteria according to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) – single exposure, inhalation are not met since the performance of an acute inhalation toxicity test is neither technically feasible nor scientifically relevant for this type of compound.

The test material can safely be assumed to have a very low potential for human inhalation hazard during handling or application. No effects are expected at the guidance value, inhalation for a Category 1 classification of <= 1 mg/L/4h and at the guidance value, oral for a Category 2 <= 5 mg/L/4h - > 1 mg/L/4h. No additional classification required.