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Key value for chemical safety assessment

Effects on fertility

Description of key information

In a combined 28 -day repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) of dilithium tetraborate by oral gavage in rats, no treatment-related changes were noted the reproductive parameters examined in this study (i.e. mating and fertility indices, precoital time, number of implantation sites, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs) up to the highest dose level tested ( 150 mg/kg). The NOAEL (reproductive effects) based on the outcome of this study is therefore 150 mg/kg (bw).

At physiological pH, both lithium tetrahydroxyborate and dilithium tetraborate dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. It will the boric acid component of the substances which will drive the mammalian toxicity endpoints. In order to minimise animal testing, only one substance in the category was tested, dilithium tetraborate. For all other substances in the category including lithium tetrahydroxyborate, read-across is proposed.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
At physiological pH, the substances dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. It will the boric acid component of the substances which will drive the mammalian toxicity endpoints. In order to minimise animal testing, only one substance in the category was tested, dilithium tetraborate. For all other substances in the category, read-across is proposed.
Dose descriptor:
NOAEL
Effect level:
>= 150 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOAEL
Effect level:
ca. 50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: based on reduced gestation index, marked
Key result
Reproductive effects observed:
no
Conclusions:
In a combined 28 -day repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) of dilithium tetraborate by oral gavage in rats, no treatment-related changes were noted the reproductive parameters examined in this study up to the highest dose level tested. The reproduction NOAEL is therefore at least 150 mg/kg.

The NOAEL (Developmental toxicity) was determined to be 50 mg/kg (bw) - this is based on reduced gestation index, marked reductions in post-implantation survival, live litter size, live birth, viability and lactation indices, a high number of total litter losses, and reduced pup birth weight and postnatal growth at 150 mg/kg 
The parental NOAEL was determined to be 50 mg/kg (bw) - this is based on reduced body weight gain at gestation and lactation.

Dilithium tetraborate and all other substances in this category rapidly dissociate in aqueous media yielding the same compound, boric acid/borates at physiological pH. It is therefore expected that lithium tetrahydroxyborate will exhibit the same prenatal developmental toxicity.
Executive summary:

In a combined 28 -day repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) of dilithium tetraborate by oral gavage in rats using doses, no treatment-related changes were noted the reproductive parameters examined in this study (i.e. mating and fertility indices, precoital time, number of implantation sites, estrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs) up to the highest dose level tested ( 150 mg/kg)

Developmental toxicity was observed at 150 mg/kg.  There were no explanatory morphological findings in parental reproductive organs.  The developmental toxicity at 150 mg/kg was characterized by a reduction in the gestation index, marked reductions in post-implantation survival index, live litter size, live birth index, viability index and lactation index, and reduced birth weight and postnatal growth of pups.  

The parental NOAEL based on the outcome of this study is 50 mg/kg (bw). This is based on reduced body weight gain at gestation and lactation.

At physiological pH, both lithium tetrahydroxyborate and dilithium tetraborate dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. It will the boric acid component of the substances which will drive the mammalian toxicity endpoints. In order to minimise animal testing, only one substance in the category was tested, dilithium tetraborate. For all other substances in the category including lithium tetrahydroxyborate, read-across is proposed.

A reproductive classification of Category 2 is therefore proposed for all borate substances.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
chronic
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key information

In a combined 28 -day repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD TG 422) of dilithium tetraborate by oral gavage in rats, developmental toxicity was observed at 150 mg/kg.  This was characterized by a reduction in the gestation index, marked reductions in post-implantation survival index, live litter size, live birth index, viability index and lactation index, and reduced birth weight and postnatal growth of pups.

 

The developmental NOAEL based on the outcome of this study is therefore 50 mg/kg (bw).

At physiological pH, both lithium tetrahydroxyborate and dilithium tetraborate dissociate and release boric acid and lithium ions as a result of relevant transformation pathways. It will the boric acid component of the substances which will drive the mammalian toxicity endpoints. In order to minimise animal testing, only one substance in the category was tested, dilithium tetraborate. For all other substances in the category including lithium tetrahydroxyborate, read-across is proposed.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
chronic
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

Justification for classification or non-classification

On the basis of the developmental effects observed in the oral gavage OECD TG 422 study with dilithium tetraborate, a classfication of Category 2 - H361d: Suspected of damaging the unborn child. The same classification is proposed for all lithium borate substances in the category approach.

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