Barium sulphide

Carcinogenicity

Description of key information

There was no evidence of carcinogenic activity (showing no chemical related increase of malignant or benign neoplasms) of barium chloride dihydrate in both sexes of rats that received 500, 1250, and 2500 ppm. Thus, the concentration of 2500 ppm BaCl2 *2 H2O represents a NOAEL (corresponding to Ba doses of 60 and 75 mg/kg bw/d to male and female rats, respectively). The NOAEL was derived by a toxicologist that reviewed the article.
There is no conclusive evidence for any carcinogenic potential of H2S in the public domain, despite that it is well-known that H2S can elicit local effects in the respiratory tract. Upon systemic availability, sulfides are rapidly oxidised and excreted renally as sulfates. Regarding sulfur and sulfates, there is a general opinion that these compounds are essential for life and do not pose a risk for humans.
Thus, in the absence of any conclusive human or animal evidence for any carcinogenic effect, the complete lack of genotoxicity of sulfides, and given the metabolic profile and natural geogenic ubiquitous presence of sulfides in the environment, there is no need for the conduct of a carcinogenicity study for inorganic sulfides.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

74 mg/kg bw/day

Study duration:

chronic

Species:

rat

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

There is no conclusive evidence for any carcinogenic potential of H₂S in the public domain, despite that it is well-known that H₂S can elicit local effects in the respiratory tract. Upon systemic availability, sulfides are rapidly oxidised and excreted renally as sulfates. Regarding sulfur and sulfates, there is a general opinion that these compounds are essential for life and do not pose a risk for humans.

Thus, in the absence of any conclusive human or animal evidence for any carcinogenic effect, the complete lack of genotoxicity of sulfides, and given the metabolic profile and natural geogenic ubiquitous presence of sulfides in the environment, there is no need for the conduct of a carcinogenicity study for inorganic sulphides.

Furthermore, there was no evidence of carcinogenic activity (showing no chemical related increase of malignant or benign neoplasms) of barium chloride in both sexes of rats and mice that received 500, 1250, and 2500 ppm. Since read across from barium chloride to barium sulphide is considered to be fully justified there is no need for the conduct of a carcinogenicity study for any barium substances.

Thus, according to Directive EEC 67/548 and to EC Regulation No. 1272/2008, barium sulfide should not be considered to have a carcinogenic potential, and hence no classification or labelling is required.

Additional information

READ ACROSS CONCEPT

Valid studies on carcinogenicity for barium sulfide are not available. Therefore, because of the lack of appropriate experimental data, read-across from studies with H₂S and BaCl₂is proposed based on the following reasoning:

 

Read-across to H₂S:

The readily water-soluble compound barium sulfide will initially dissociate upon dissolution in water and/or relevant physiological media into barium and sulfide ions.

 

However, sulfide anions will react with water in a pH-dependant reverse dissociation to form hydrogensulfide anions (HS-) or H₂S, respectively, according to the following equation:

 

H₂S  ↔  H⁺  +  HS^-  ↔  2H⁺  +  S^2-

 

The dissociation behaviour is presented in the Hägg graph reported under IUCLID section 5.1.2 Hydrolysis.

 

The pKa values for the first and second dissociation steps of H2S are 7.0 and 12.9 (for details, refer to the IUCLID section on dissociation constant), respectively. Therefore, at neutral physiological pH values, hydrogen sulfide in the non-dissociated form (H2S) and the hydrogen sulfide anion (HS-) will be present in almost equimolar proportion, whereas only very small amounts of the sulfide anion (S2-) will be present. Conversely, at gastric pH (pH 1-2), non-dissociated H2S will be the predominant species.

 

In conclusion, under physiological conditions, inorganic sulfides or hydrogensulfides as well as H2S will dissociate to the respective species relevant to the pH of the physiological medium, irrespective of the nature of the “sulfide”, which is why read-across between these substances and H2S is considered to be appropriate without any restrictions for the purpose of hazard and risk assessment of barium sulfide.

  

Read-across to Ba(OH)2 and BaCl2, respectively:

 

Upon dissolution in water and/or physiological media, dissociation of barium sulfide to release Ba²⁺ions may initially be expected.

 

However, based on the established fact that barium ions may form poorly soluble species for example with physiologically present carbonate ions, the bioaccessibility/bioavailability may vary between different physiological conditions. Notwithstanding this limitation, it is considered justified to read-across from available data either on barium hydroxide (similar water solubility) and/or barium chloride (higher water solubility), the latter representing a conservative approach). In this context, the water solubility of a substance is used as a first approximation of bioavailability:

 

- barium chloride is highly water soluble with ca. 375 g/L at 20 °C/pH ca. 6.5 (510.4 g/L at pH 1.5)

- barium hydroxide is also highly water soluble (37.4 g/L at 20 °C/pH > 13).

 

In comparison, the water solubility of barium sulfide is 73.5 g/L at 20 °C (pH 13.7; saturated solution).

 

In conclusion, read across from barium chloride and barium hydroxide to barium sulfide is considered as justified since the toxicity of these substances may reasonably be considered to be determined by the availability of barium cations. It is noted that although BaS is a strong base, substantial neutralisation in the gastrointestinal tract at pH-levels of approx. 1.5 – 2 may nevertheless be anticipated.

Barium

According to the NTP study performed 1994 with barium chloride, there was no evidence of carcinogenic activity (showing no chemical related increase of malignant or benign neoplasms) of barium chloride in both sexes of rats and mice that received 500, 1250, and 2500 ppm. Thus, the concentration of 2500 ppm represents a NOAEL (corresponding to barium doses of 60 and 75 mg/kg bw/d to male and female rats, respectively, and 160 and 200 mg/kg bw/d to male and female mice, respectively). Based on this value the NOAEL for BaS is calculated at 74 mg/kg bw/day. No classification of the substance as CMR substance is required.

Sulfides and hydrogen sulfides

An extensive literature search and evaluation programme on animal and human repeated dose toxicity data of sodium sulfide, sodium hydrogensulfide and dihydrogen sulfide has been conducted. However, no adequate data from carcinogenicity studies are available.Therefore, information from other substances related to sulfides is considered for evaluation of the carcinogenic hazard.

Justification for selection of carcinogenicity via oral route endpoint:
Only one study was made available that is considered to fulfil the requirements for the carcinogenic endpoint for barium sulfide. The NTP study was performed with barium chloride dihydrate and read across is considered to be fully justified (see discussion). There is no need to initiate a study with inorganic sulfide, assuming the complete lack of genotoxicity of sulfides, and given the metabolic profile and natural geogenic ubiquitous presence of sulfides in the environment.