Registration Dossier

Administrative data

Description of key information

Overall, the following NOAELs are taken forward (see discussion):
 - 91d dermal systemic NOAEL = 875 mg/kg bw/day based on registered substance aluminium zirconium chloride hydroxide (derived from a NOAEL for an aluminium zirconium glycinate compound ("ZAG")).
- 28d oral systemic NOAEL = 464 mg based on registered substance aluminium zirconium chloride hydroxide (derived from a NOAEL for basic aluminium chloride). This NOAEL is lower than when calculated using an equivalent results for the zirconiummoiety).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
464 mg/kg bw/day
Study duration:
subacute
Species:
rat

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 adverse effect observed
Dose descriptor:
NOAEL
875 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Species:
rabbit

Additional information

Repeated dose inhalation toxicity:

Repeated dose toxicity testing via the inhalation route is not considered to be required, since (i) the intended use of aluminium zirconium chloride hydroxide is only in topical cosmetic products, i.e. antiperspirant creams, roll-ons and sticks (within preparations), and (ii) the bulk of material placed on the market is in concentrated liquid form, which imparts a gel-like consistence to this material. Based on the latter and the corresponding negligible vapour pressure, dermal contact is the most relevant route of exposure. Only minor volumes of powder forms are placed on the market, which in turn are used only during production and formulation into wet preparations (solutions, suspensions). The potential for inhalation exposure to these powders is in fact low, based on particle size and dustiness considerations (see also sections 4.5 (particle size/granulometry) and 7.2.2. (acute inhalation toxicity) in the technical dossier.

 

Repeated dose dermal toxicity (read-across from similar zirconium/aluminium compound (which contains some extra glycine)):

A 91-d percutaneous toxicity study in rabbits with an aluminium zirconium chloride hydroxide glycinate (ZAG) is available, in which 3 male and 3 female New Zealand White rabbits received a single dose level of 2000 mg/kg/day on 5 days per week for 13 weeks; a concurrent vehicle (distilled water) control group was included. There were no clinical signs or any mortality, no effects on body weight/ food consumption, and only mild skin irritation (scores of 0.5 or less for erythema only). There were no adverse effects on haematology and clinical chemistry, and histopathology was negative except for very slight to slight inflammatory cell infiltration in the dermis of all rabbits and very slight hyperkeratosis and acanthosis in 2 rabbits; however, these microscopic lesions in treated rabbits were considered by the investigators as common also for untreated rabbits in the laboratory, and were therefore not considered significant. Based on the described effects, the authors concluded on a NOAEL of 2000 mg/kg bw/d, expressed as based on the test item. The exact Al and Zr content of the test item used was not stated in the report. However, based on industry information, a typical content of 17.75% Al and 10.5 % Zr in the test substance "Impalpable ZAG" is assumed. A 47.5% aqueous solution of this test item was used for application. Thus, the NOAEL of 2000 mg/kg bw/day based on the applied test item corresponds to 170 and 100 mg/kg/day based on Al and Zr respectively.

For the registered substance an average content of Al = 19.4% and of Zr=10.3% is used for the stoichiometeric recalculation to a NOAEL based on the registered substance. NOAELs for the registered substance = ca. 875 mg/kg bw/day (calculated via Al content) or ca. 970 mg/kg bw/day (calculated via Zr content) can be derived. The lower dermal NOAEL of 875 mg/kg bw/day, based on the registered substance, is taken forward.

 

 

Repeated dose oral toxicity (read-across from other Al and Zr compounds):

 

Repeated dose oral toxicity data specifically for aluminium zirconium chloride hydroxide are not available. The aluminium and zirconium moieties of the substance are characterised by similarly poor dermal, inhalation and oral absorption. Nevertheless, as supporting data for the assessment of systemic toxicity, read-across from 28d oral toxicity studies with basic aluminium chloride and zirconium acetate can be made base on the common metal ions being relevant under physiological conditions:

 

Read-across for oral repeated dose toxicity based on Al moiety (from basic aluminium chloride)

In a combined 28-day oral repeated dose toxicity study with reproduction/developmental toxicity screening with basic aluminium chloride involving dosing at 40, 200 and 1,000 mg/kg bw/d, the following results were obtained:

No clinical signs and no effects on organs weights were noted, but body weight gains and food consumption were reduced at 1,000 mg/kg bw/d. There were slight but statistically significant effects on haematocrit and platelet counts, as well as in clinical chemistry (ALP and albumin decreased, potassium and phosphate increased at 1,000 mg/kg bw/d). Merely mild to moderate sub-acute inflammation of the glandular mucosa and minimal to moderate superficial eosinophilic spheroids was observed histopathologically in all examined animals of both sexes at 1000 mg/kg bw/d.

Based on the described effects, the authors concluded on a NOAEL for local effects (males) of 200 mg/kg bw/d, and an overall NOAEL for systemic effects of 1,000 mg/kg bw/d (males and females). Based on the Al content of the test item basic aluminium chloride, the NOAEL for systemic effects is 90 mg/kg bw/day. There were no effects whatsoever on reproductive performance or on organs of reproduction, either on organ weights or upon histopathological investigation.

For the registered substance an average content of Al = 19.4% is used for the stoichiometric recalculation to a NOAEL based on the registered substance. NOAEL for the registered substance = ca. 464 mg/kg bw/day (calculated via Al content).

 

Read-across for oral repeated dose toxicity based on Zr moiety (from zirconium acetate)

In a 28 -day oral repeated dose toxicity study with the test item zirconium acetate, there were no toxicologically relevant effects in any dose group (100, 300 and 1000 mg/kg bw/day based on the test item, corresponding to 53, 159 and 530 mg Zr/kg bw/day. The NOAEL is 530 mg Zr/kg bw/day based on zirconium.

For the registered substance an average content Zr is 10.3% is used for the calculation of a NOAEL based on the registered substance. NOAEL for the registered substance = 5145 mg/kg bw/day (calculated via Zr content).

 

The lower oral NOAEL of 464 mg/kg bw/day, based on the registered substance (calculated via Al content), is taken forward.

 

 

 

Justification for classification or non-classification

In dermal and oral repeated dose toxicity studies relevant for aluminum zirconium chloride hydroxide (see also discussion), there were no effects observed which would result in the need to classify this substance for repeated dose toxicity.