Registration Dossier

Administrative data

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:
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.