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Key value for chemical safety assessment

Effects on fertility

Description of key information
This information is not available.
Additional information

Justification for read-across

Read-across from magnesium chloride hexahydrate to magnesium carbonate is justified on the following basis.

 

Due to the presence of acid, mainly in the form of hydrochloric acid, in the stomach, magnesium carbonate will be converted into magnesium chloride when orally ingested. Furthermore, magnesium chloride is significantly more soluble than the carbonate salt and therefore represents the worst case in terms of its bioavailability for systemic absorption.

In addition, both salts have been shown to have no acute toxicity and do not exhibit evidence of systemic toxicity when tested at a concentration of 2000 mg/kg bw in acute oral studies.

Magnesium carbonate and magnesium chloride also occur in the natural environment and humans are widely exposed to naturally occurring magnesium carbonate and chloride, e.g. via drinking water and food on a day to day basis. Ingested magnesium, carbonate and chloride ions are actively regulated by the body. Any systemic toxicity is likely to be caused by absorption of the magnesium ion rather than either the carbonate or chloride counterions and hence studies on magnesium salts can be read across from one to the other.

This study is therefore deemed reliable for read across to magnesium carbonate as it represents the worst case for potential reproductive toxicity.

Review of the available toxicity data

A 28 day repeat dose oral toxicity study combined with a reproduction/ developmental toxicity screening test was performed in the rat in accordance with OECD TG 422 (BSL, 2010). Magnesium chloride hexahydrate was administered daily by gavage to three groups of Wistar rats for 14 days pre-mating and 14 days mating in both male and females, during gestation period and up to post natal day 3 in females. Males were dosed for 28-29 days. Dose levels of 0, 250, 500 and 1000 mg/kg bodyweight/day were used.

The repeated dose administration of magnesium chloride hexahydrate revealed no major toxicological findings. Statistical analysis of reproduction and litter data revealed no treatment related effects and survival of the pups from post-natal day 0 to 4 remained unaffected in all groups. Based on the data generated from the study, the NOAEL for reproduction/ developmental toxicity is believed to be 1000 mg/kg bw/day for magnesium chloride hexahydrate. This study is directly applicable to magnesium carbonate and hence the equivalent NOAEL for magnesium carbonate is 414 mg/kg bw/day.


Short description of key information:
The read-across substance, magnesium chloride hexahydrate, showed no signs of reproduction/developmental toxicity in an OECD 422 reproduction/developmental screening toxicity test at doses up to 1000 mg/kg bw/day.

Effects on developmental toxicity

Description of key information
The read-across substance, magnesium chloride hexahydrate, showed no signs of developmental toxicity in a teratogenicity study or in an OECD 422 repeat-dose toxicity reproduction/developmental toxicity screening study.
Additional information

Justification for read-across

Read-across from magnesium chloride hexahydrate to magnesium carbonate is justified on the following basis.

 

Due to the presence of acid, mainly in the form of hydrochloric acid, in the stomach, magnesium carbonate will be converted into magnesium chloride when orally ingested. Furthermore, magnesium chloride is significantly more soluble than the carbonate salt and therefore represents the worst case in terms of its bioavailability for systemic absorption.

In addition, both salts have been shown to have no acute toxicity and do not exhibit evidence of systemic toxicity when tested at a concentration of 2000 mg/kg bw in acute oral studies.

Magnesium carbonate and magnesium chloride also occur in the natural environment and humans are widely exposed to naturally occurring magnesium carbonate and chloride, e.g. via drinking water and food on a day to day basis. Ingested magnesium, carbonate and chloride ions are actively regulated by the body. Any systemic toxicity is likely to be caused by absorption of the magnesium ion rather than either the carbonate or chloride counterions and hence studies on magnesium salts can be read across from one to the other.

This study is therefore deemed reliable for read across to magnesium carbonate as it represents the worst case for potential developmental toxicity.

Review of the available toxicity data

A study investigating the teratogenicity of magnesium chloride hexahydrate is available (Usami, 1996). The test material was dissolved in distilled water and was administered to pregnant Wistar rats by gavage once a day from day 6 through to 15 of pregnancy at doses of 0, 200, 400 and 800 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their foetuses examined for malformation.

The highest dose used in this study (800 mg/kg/day), which did not cause any mortalities or evidence of treatment related toxicity, did not increase or induce any teratogenicity in the foetuses. In skeletal variation tests in the foetuses, there were no effects on extra ribs (this is considered to be an indication of low dose toxicity of substances); therefore, it is unlikely that effects would have been seen at higher doses. It was concluded that magnesium chloride hexahydrate has no teratogenicity in rats when given by gavage. The NOAEL for the test material was estimated to be >800 mg/kg bw/day for both pregnant rats and rat foetuses. This study is directly applicable to magnesium carbonate and hence the equivalent NOAEL for magnesium carbonate is >331 mg/kg bw/day for both pregnant rats and foetuses.

No developmental effects were seen in an OECD TG 422 combined repeated dose toxicity study with reproduction/developmental toxicity screening test in which magnesium chloride hexahydrate was adminstered by gavage at doses up to 1000 mg/kg bw/day, equivalent to 414 mg/kg bw/day fro magnesium carbonate.

Justification for classification or non-classification

Under the conditions of the OECD TG 422 study, magnesium chloride hexahydrate administered to male and female rats at dose levels up to 1000 mg/kg bw/day for a period of up to 48 days was not toxic to reproduction and had no effect on fertility or development. No treatment-related effects were observed for reproduction; hence, the NOAEL for reproductive/ developmental toxicity was considered to be 1000 mg/kg bw/day.

The developmental toxicity study also demonstrated that magnesium chloride hexahydrate was not teratogenic at the concentrations used. Since no adverse effects were noted at the highest dose level tested, the NOAEL for teratogenic and maternal toxic effects in rats is >800 mg/kg bw/day. Both these studies are applicable to magnesium carbonate.

Based on these results, magnesium carbonate does not warrant classification under either the DSD or CLP.

Additional information