Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
no relevant information; for further information see secion 12 "literature search"
Effect on fertility: via oral route
Quality of whole database:
Only a screening test is available. However, based on this study there are no indications of a substantial impairment of fertility in rats up to the highest dose tested. Thus, the NOAEL was 4000 ppm (to average doses of 201.5 and 179.5 mg Ba/kg bw/d to male and and female rats, respectively). No-observed-adverse-effect levels (NOAELs) on developmental toxicity for rats of 4000 ppm were derived. 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. Nevertheless, a decision on the registrant’s testing proposal for a study investigating the effects on fertility has not yet been taken by ECHA.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

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 and 2,000 ppm in mice can be derived (see "short description of key information").

 

For this reason, a testing proposal for a study investigating the effects on fertility was included into the registration dossier but a final decision has not yet been taken by ECHA.


Short description of key information:
Screening study:
Fertility impairment in female rats: NOAEL of 179.5 mg Ba2+/kg bw/d; relates to 272 mg Barium chloride/kg bw/day (Dietz et al., 1992)
Fertility impairment in male rats: NOAEL of 201.5 mg Ba2+/kg bw/d; relates to 306 mg Barium chloride/kg bw/day (Dietz et al., 1992)

Effects on developmental toxicity

Description of key information
Developmental toxicity: a NOAEL of >=85.3 mg BaCl2/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
85.3 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is fully acceptable
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

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 20. 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 30 mg/kg body weight barium chloride dihydrate (25.6 mg/kg bw barium chloride)). In absence of developmental effects, the NOAEL for prenatal developmental toxicity in the rat was ≥ 100 mg/kg body weight barium chloride dihydrate (≥85.3 mg/kg bw barium chloride).

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 selection of Effect on developmental toxicity: via oral route:
Barium dichloride dihydrate was evaluated recently in a GLP compliant oral prenatal toxicity study accorrding to OECD guideline 414. The NOAEL is reported as re-calculated barium dichloride.

Justification for classification or non-classification

No classification is required based on the results of the prenatal developmental toxicity study. Further classification and labelling will be postponed till the results of thestudy investigating the effects on fertilityare available.