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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Effects on fertility:

Only two studies (NTP and Dietz) exist in which a dose-response relationship of different adverse effects on fertility after oral administration of barium chloride was investigated. These studies (see section 7.8.1) which were published in peer-reviewed journals were examined with respect to their adequacy for the derivation of NOAEL/LOAEL values for fertility impairment.

Based on these limited investigations with barium chloride as described above, a lack of fully, guideline conform data must be noted. Tentatively, the premating study by Dietz et al. (1992) on rats and mice may be considered as the only acceptable study for the derivation of a preliminary NOAEL for fertility effects of soluble barium compounds. This study investigated the occurrence of different adverse effects in male and female rats and mice and their offspring related to barium chloride exposure via drinking water. A tentative NOAEL for fertility impairment of 4,000 ppm in rats can be derived corresponding to average doses of 201.5 and 179.5 mg Ba/kg bw/d to male and and female rats, respectively. However, this NOAEL is of limited value to evaluate the potential for barium to induce developmental effects because there was no exposure of the females during gestation. An EOGRTS with barium chloride is ongoing. Read across to barium hydroxide is considered appropriate (see discussion below).

Read across from BaCl2*2H2O to Ba(OH)2:

The toxicity of barium hydroxide 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 chloride is highly water soluble with ca. 263 g/L at pH ca. 6.5 (510.4 g/L at pH 1.5). Also the water solubility of barium hydroxide is high (37.4 mg/L at pH > 13). Hence, any read across from barium chloride to barium hydroxide is considered to be justified and will likely lead to rather conservative no-effect levels.It is noted; although Ba(OH)2is a strong base (pH 13 for a 10% solution) it will be neutralised within the gastrointestinal tract (pH approx. 1.5 - 2).


Effects on developmental toxicity

Description of key information
a NOAEL of ≥ 70.2 mg Ba(OH)2/kg was derived in an oral developmental toxicity study according to OECD 414.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
70.2 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Read across from BaCl2*2H2O toBa(OH)2:

The toxicity of barium hydroxide 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 chloride is highly water soluble with ca. 263 g/L at pH ca. 6.5 (510.4 g/L at pH 1.5). Also the water solubility of barium hydroxide is high (37.4 mg/L at pH > 13). Hence, any read across from barium chloride to barium hydroxide is considered to be justified and will likely lead to rather conservative no-effect levels.It is noted; although Ba(OH)2is a strong base (pH 13 for a 10% solution) it will be neutralised within the gastrointestinal tract (pH approx. 1.5 - 2).

Developmental toxicity

Developmental toxicity of barium chloride dihydrate was evaluated in a recent prenatal developmental toxicity study by daily administration of the test item at dose levels of 0, 10, 30 or 100 mg BaCl2 * 2 H2O/kg body weight to pregnant rats from gestation day 1 up to and including gestation day(Theuns-van Vliet, 2014) .

No effects on body weights, food consumption and clinical signs were observed. Maternal toxicity was evidenced by the spontaneous deaths of two animals on gestation day 21 only and the conditional decline of another animal on gestation day 21 in the high dose group (100 mg BaCl2 * 2 H2O/kg bw).

No developmental toxicity or treatment-related observations, whatsoever in external, visceral and skeletal foetal examinations were observed in any dose level.

The NOAEL for maternal toxicity was therefore 16.9 mg Ba2 +/kg bw/d (corresponding to 21.1 mg Barium hydroxide/kg bw/day). In absence of developmental effects, the NOAEL for prenatal developmental toxicity in the rat was ≥ 56.2mg Ba2 +/kg bw/d (corresponding to 70.2 mg Barium hydroxide/kg bw/day).

Furthermore, tentative NOAEL values for developmental toxicity of 4,000 ppm and 2,000 ppm for rats and mice, respectively, are also reported in the study by Dietz et al. (1992). However, these NOAELs are of limited value to evaluate the potential for barium to induce developmental effects because the study design did not include prenatal exposure of the female animals to barium dichloride dihydrate. Therefore, this study has to be considered as inadequate for the assessment of the potential to induce developmental toxicity and cannot be used in a regulatory context.

Justification for classification or non-classification

No classification is required based on the results of the prenatal developmental toxicity study with barium chloride. Read across to barium hydroxide is considered appropriate (see discussion above). Further classification and labelling will be postponed till the results of the study investigating the effects on fertility are available.