[carbonato(2-)]hexadecahydroxybis(aluminium)hexamagnesium

Endpoint summary

Description of key information

Read-across from analogue substances was applied.
Key values for risk assessment: 
28-d NOAEL 1000 mg/kg bw/d (read-across from substance with EC no. 423-570-6)
chronic NOAEL: 605 mg/kg bw/d  (in analogy to RIVM decision for Alcamizer P93, dated 23 October 2007, BMS071023.03)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study performed in accordance with OECD guideline and in compliance with GLP guidelines. As the study is performed with a substance analogue, in accordance with REACH guidance the maximum reliability for read-across data is 2. Read-across is justified because of the similar chemical nature of the target substance compared to the analogues. The read-across rationale can be found in the analogue approach document attached in Section 13.

Qualifier:

according to guideline

Guideline:

other: EEC-Directive 92/69 B.7

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: destilled water

Details on oral exposure:

Method of administration:
oral gavage

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

amples of test substance formulations, prepared after the end of the in-life phase, were taken at 90% height (Top = T), 50% height (Middle = M) and 10% height (Bottom = B) of the container. Samples were stored in a refrigerator in the dark until shipment to TNO, Zeist, The Netherlands, where they were analysed for free Aluminium.

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 50 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 50 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Control animals:

yes, concurrent vehicle

Observations and examinations performed and frequency:

Mortality/Viability: Twice daily.
Clinical signs: At least once daily from day 1 onwards.
Body weights: On days 1, 8, 15, 22 and 28.
Food consumption: Weekly.
Clincal laboratory investigations: Blood samples were collected under light ether anaesthesia immediately prior to
post mortem examination. Blood samples were drawn from the retro-orbital sinus of all rats/sex/group.

Sacrifice and pathology:

All animals assigned to the study were necropsied and descriptions of all macroscopic
abnormalities recorded. Samples of the following tissues and organs were collected from all animals at
necropsy and fixed in neutral phosphate buffered 4% formaldehyde solution:
Adrenal glands
Heart
Kidneys
Liver
Spleen
Stomach
Testes
All gross lesions

Organ weights: The following organ weights (and terminal body weight) were recorded from the
surviving animals on the scheduled day of necropsy:
Adrenal glands
Heart
Kidneys
Liver
Spleen
Testes

Histopatholgy: Slides of adrenals, heart, kidneys, liver, spleen, stomach and testes, collected at the scheduled sacrifice from all animals of the control and the highest dose group, and all gross lesions of all animals were examined by a pathologist.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

Clinical observations:
No signs of toxicity or behavioural changes that were
considered to be related to treatment.

Laboratory findings:
No findings on haematology or clinical biochemistry
parameters.

Effects in organs:
No findings that were considered to have arisen as a result
of treatment.

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Critical effects observed:

not specified

Comments:
None.

Conclusions:

Classified as: Not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Endpoint derived based on RIVM decision for Alcamizer P93, dated 23 October 2007, BMS071023.03).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Based on the Dutch Competent Authority Risk Assessment dated October 23, 2007 (BMS071023.03) of Aluminium-magnesium-zinc-carbonate-

hydroxide (an analogue substance), [carbonato(2-)]hexadecahydroxybis(aluminium)hexamagnesium) is of no concern for man and need not be considered further - data currently available are sufficient to allow the notification of this substance above 1000 tonnes/year.

* Aluminium-magnesium-zinc-carbonate-hydroxide (EC no. 423-570-6):

Aluminium-magnesium-zinc-carbonate-hydroxide was tested in a subacute 28-day oral toxicity test (EEC-Directive 92/69 B.7 (according to GLP principles)):

The substance was administered (gavage) to female and male Wistar rats. The dose range was as follows: 0, 50, 200 and 1000 mg/kg bw/day for 28 days - 5 animals per group. No treatment related effect was observed. It was concluded that the NOAEL was 1000 mg/kg bw/day, the highest dose tested.

For chronic toxicity the NOAEL was derived from the NOAEL for Al³⁺ and the content of Al in the substance to be 605 mg/kg bw/d.

Supporting data [carbonato(2-)]hexadecahydroxybis(aluminium)hexamagnesium: 180 days oral gavage repeated dose toxicity test in rats:

NOAEL > 2000 mg/kg/day.

No data is available on dermal or inhalation toxicity.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Reliable endpoint available for analogue.

Justification for classification or non-classification

Based on the current data for analogues no classification is needed for systemic toxicity after repeated exposure for Magnesium-Aluminium-Hydroxide-Carbonate according to Regulation (EC) No 1272/2008.