Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
159 mg/kg bw/day
Additional information

There are no data on toxicity to reproduction available for silicic acid, lithium salt. However, there are data available for other soluble silicates. Thus, read-across was conducted based on analogy approach.


In a limited 4-generation study, Smith et al. (1973) assessed the effect of silicic acid, sodium salt in rats. The animals were exposed to 79 and 159 mg/kg bw/day via drinking water from weaning until mating. The average litter sizes were 9.6, 6.8 and 8.4 animals/litter for the control and the 79 and 159 mg/kg bw/day dose goups, respectively. Survival of offspring until weaning was poor, even in the controls (35, 24 and 11% at 0, 79 and 159 mg/kg bw/day, respectively). The total number of offspring born was reduced to 67% of the controls at 79 mg/kg bw/day and to 80% of the controls at 159 mg/kg bw/day. Litters born to females receiving silicates were frequently stillborn or small and weak, with survival limited to only a few days. In addition cannibalism was prevalent and necrosis of the tail and occasionally the feet was observed in pubs of silicate-treated animals.

The NOAEL for parental animals was determined to be >=159 mg/kg bw/day. For the F1 generation no NOAEL was identified. However, severe limitations of the study and intercurrent deaths, including controls make it however difficult to draw any firm conclusion from this study.


In oral repeated dose toxicity studies with rats, mice and dogs, the macroscopic and microscopic examination of reproductive organs (e.g. testes, ovaries) did not reveal any treatment-related effects (Sawai et al., 1980; Ito et al., 1975; Newberne and Wilson, 1970). Kamboj and Kar (1964) did not find testicular effects of sodium silicate injected either subcutaneously or intratesticularly in male rats.

Since silicic acid, lithium salt contains depending on its molar ratio 3.4 - 7% lithium (MR: 2.8 - 6.3), which is assumed to be bioavailable after ingestion, the developmental toxicity of lithium have also to be taken into consideration for assessment.

In an inadequately reported study by Mrozka et al. (1983) the effect of lithium on reproduction was studied in mice. In mice given 8.4 mM lithium (corresponding to 743 mg silicic acid, lithium salt (MR: 2.8)/kg bw/day) in drinking water before mating and during gestation and lactation following changes in the reproduction capacity were observed: increase of the length of time between litters by about three days and reduction of the total number of litters compared to controls. In animals exposed to lithium 5 weeks before mating and onwards delayed postnatal growth and development of all pups in litters were described.

In further publications, significant reductions in the number of corpora lutea (Trautner et al., 1958, RL3) and perturbation of spermatogenesis (Ghosh et al., 1991) were reported in animals. In in vitro studies with human sperm, decreased motility was observed at concentrations comparable with those reported in serum after oral administration of lithium to patients. However, the amount of evidence and the quality of the human in vitro studies is unsufficient for a conclusion on the effects on fertility (Lagerkvist and Lindell, 2002).



Ghosh, P.K. et al. (1991) Effect of lithium chloride on spermatogenesis and testicular steroidgenesis in mature albino rats: duration dependent response. Life Sciences 48:649 -657

Short description of key information:
multigeneration study, rat, NOAEL(P) >= 159 mg/kg bw/day (RA from silicic acid, sodium salt)
No NOAELs could be identified in tests with the surrogate substance lithium chloride.

Effects on developmental toxicity

Description of key information
developmental study, mouse: NOAELdevelopmental >= 200 mg/kg bw (RA from disodium metasilicate)
prenatal developmental study (OECD 414): NOELmaternal: 30 mg/kg bw/day (corresponding to 80 mg silicic acid, lithium salt (MR: 2.8)/kg bw/day); NOELembryotoxicity >= 90 mg/kg bw/day (corresponding to >= 241 mg silicic acid, lithium salt (MR: 2.8)/kg bw/day) (RA from dilithium carbonate)
Effect on developmental toxicity: via oral route
Dose descriptor:
200 mg/kg bw/day
Additional information

There are no data for silicic acid, lithium salt. However, there are reliable data for the substance disodium metasilicate. Thus, read-across was performed based on an analogue approach.


In a non-standard developmental study, pregnant mice were orally administered by gavage 12.5, 50 and 200 mg/kg bw/day disodium metasilicate in aqueous solution from day 0 to 18 of gestation (Saiwai et al., 1980).

Two dams died in the middle and high dose groups. No treatment-related effects were observed on body weight, organ weights and dissection findings among mother animals. On day 18 of gestation, foetuses were delivered by hysterectomy and examined. No differences were observed between dose and control groups for the parameters: number of pregnancies and living or dead foetuses, body weight and malformation of inner organs and the skeleton. The observed skeletal malformations in neonates like cervical vertebrae, tail vertebrae and vomer adhesion also occurred in the controls and did not show a dose-dependent correlation. 10 mother animals were allowed to deliver their young naturally. The neonates were observed for 30 days. Litter size and fertility index were not significantly affected up to and including the highest dose tested. Body weight, organ weights and behavioural development did not reveal any differences compared to the control. No malformations of the skeleton or the inner organs of the foetuses delivered by hysterectomy were observed; the frequency of malformations and abnormalities of the external integument, like opened eyes, cleft palate and exencephaly showed a slight tendency toward dose dependence, but it was lower than in the control. A dose-related decrease in the number of neonates was observed, however, this was not statistically significant. Under the conditions of this study, no developmental effects were observed up to and including the highest dose tested, thus the NOAEL for developmental toxicity was determined to be >= 200 mg/kg bw/day.


Since silicic acid, lithium salt contains depending on its molar ration 3.4% - 7% lithium (MR: 2.8 - 6.3), which is assumed to be bioavailable after ingestion, the developmental toxicity of lithium was also taken into consideration for assessment. A reliable prenatal developmental study performed with the surrogate substance lithium carbonate is available.

In a prenatal developmental toxicity study performed according to OECD guideline 414 and EU method B.31 female rats (strain: Crl CD (SD)) were administered lithium carbonate at concentrations of 10, 30 or 90 mg/kg bw/day orally by gavage from the 6th to 19th day of pregnancy. Under the present test conditions, the no-observed-effect level (NOEL) was 30 mg lithium carbonate/kg bw/day for the dams (maternal NOEL). At 90 mg lithium carbonate/kg bw/day, pilo-erection was noted in a few dams. Furthermore, slight but significant reductions were noted for the net weight change and the food intake. There was no test item-related increase in the incidence of foetal malformations, external/ internal, skeletal or soft tissue variations or skeletal retardations. The NOEL for the foetuses was >= 90 mg lithium carbonate/kg bw/day. The toxicokinetic analysis revealed a clear dose-related systemic exposure to lithium. In conclusion, no embryotoxic properties of the test item were noted during external/ internal, skeletal and soft tissue examinations. No test item-related increase was noted in the incidence of malformations, variations or retardations, not even at the maternal-toxic dose level of 90 mg lithium carbonate/kg bw/day (corresponding to 16.9 mg lithium/kg bw/day and 241 mg silicic acid, lithium salt (MR: 2.8)/kg bw/day).

In conclusion, no indications of developmental effects for silicic acid, lithium salt are present.

Human data

Congenital defects, especially of the cardiovascular system such as Ebstein’s anomaly (a rare cardiac defect) have been reported in babies born by mothers on lithium treatment during the first trimester of pregnancy. This claim gave rise to the foundation of registers of lithium babies in Denmark and USA. A first analysis of the records of 60 children borne by mothers on lithium therapy during the first trimester or the entire pregnancy published in 1971 did not reveal any association of lithium treatment with a higher teratogenic risk (Aral and Vecchio-Sadus, 2008). In 1992, Jacobsen et al. published a prospective multicentre study of pregnancy outcome after lithium exposure during the first trimester. Since rates of major congenital malformations did not differ significantly between lithium and control groups, the authors concluded, that lithium was not a major teratogen (Lagerkvist and Lindell, 2002).



Jacobsen, S.J. et al. (1992) Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. The Lancet 339:530-533

Justification for classification or non-classification

Based on available data on toxicity to reproduction from read-across or surrogate substances, silicic acid, lithium salt does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC. No information is available on effects via lactation.