Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
464 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Data on the potential impairment of fertility specifically for aluminium zirconium chloride hydroxide (such as a 2-generation reproduction toxicity study) are not available. However, this data requirement can be waived based on (i) absence of systemic toxicity not only in a sub-chronic dermal RDT study with aluminium zirconium chloride hydroxide glycinate itself but also by way of read-across to 28d oral repeated dose toxicity studies including reproduction/developmental toxicity screening with the read-across substances “aluminium chloride” and “zirconium acetate”, (ii) and well-documented minimal to negligible bioavailability of the dissociation products (i.e., aluminium and zirconium cations) of aluminium zirconium chloride hydroxide.

In a 28 -day oral combined repeated dose toxicity study with reproduction/developmental toxicity screening study (OECD 422) with the test item basic aluminium chloride, there were no effects on fertility at either dose tested (40, 200 or 1000 mg/kg bw/day, based on the test item, corresponding to 3.6, 18 and 90 mg Al/kg bw/day). The NOAEL corresponds to 90 mg/kg bw/day based on aluminium.

In a 28 -day oral combined repeated dose toxicity study with reproduction/developmental toxicity screening study (OECD 422) with the test item zirconium acetate, there were no effects on fertility at either of the three doses (100, 300 and 1000 mg/kg bw/day, based on the test item, corresponding to 53, 159 and 530 mg zirconium/kg bw/day). The resulting NOAEL is 530 mg/kg bw/day based on zirconium.

For the calculation of a NOAEL based on the registered substance, typical contents of 19.4% and 10.3% of Al and Zr, respectively are applied. When the calculation is based on the Al content, the resulting NOAEL for fertility the registered substance is 464 mg/kg bw/day. When the calculation is based on the Zr content, the resulting NOAEL for fertility the registered substance would be 5145 mg/kgbw/day.The lower NOAEL for the registered substance of 464 mg/kg bw/day (read-across based on Al) is taken forward.

 


Short description of key information:
Read-across based on metal (Al and Zr) content: In 28-day oral repeated dose toxicity studies with screening on reproductive toxicity with the test items basic aluminium chloride and zirconium acetate, respectively, no effects on fertility were observed at the limit dose. The NOAEL for the registered substance aluminum zirconium chloride hydroxide has been calculated based on the Al content. This gives a lower NOAEL than the similar calculation based on Zr content.

Justification for selection of Effect on fertility via oral route:
Key study. Read across from study with test item "basic aluminium chloride". NOAEL recalculated based on Al content to the registered substance aluminum zirconium chloride hydroxide.

Effects on developmental toxicity

Description of key information
Oral NOAEL for developmental effects calculated based on Al content, using the NOAEL for developmental effects in an combined 28-day oral toxicity study with reproduction/developmental screening for the read-across substance basic aluminium chloride.
Dermal NOAEL for developmental effects calculated based on Al content, using the NOAEL for developmental effects in a 91-day dermal teratology study with the comparable aluminium zirconium chloride hydroxide glycinate (“ZAG”).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
464 mg/kg bw/day
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
650 mg/kg bw/day
Species:
rabbit
Additional information

A percutaneous developmental toxicity study in rabbits with the comparable aluminium zirconium chloride hydroxide glycinate (“ZAG”), as a 40% solution) is available: pregnant New Zealand White rabbits were dosed topically from days 7-18 of gestation at levels of 500 and 2000 mg/kg bw/d (concurrent vehicle control). Apart from slight skin reddening at the application site, there were no effects on maternal body weight gains, mean number of early and late resorptions, post implantation losses, implantations, and corpora lutea. The mean foetal body weights and the male and female foetal sex ratio in the environmental control group and the vehicle control group were comparable. There were no biologically meaningful differences in the mean foetal body weights or in the male to female sex ratio between either of the test item treated groups and the control groups. Based on the absence of maternal and fetal effects, the NOAEL for developmental toxicity was established at >2000 mg/kg bw/d (40% test item), corresponding to an NOAEL of 126 mg/kg bw/dbased on the analysed aluminium content and 116 mg/kg bw/day based on the analysed Zr content.

For the calculation of a NOAEL based on the registered substance, typical contents of 19.4% and 10.3% of Al and Zr, respectively are applied. When the calculation is based on the Al content, the resulting NOAEL for the registered substance is 650 mg/kg bw/day. When the calculation is based on the Zr content, the resulting NOAEL for the registered substance is 1126 mg/kg bw/day. The lower NOAEL of 650 mg/kg bw/day is taken forward for the registered substance, as the NOAEL for teratogenic effects (via the dermal route).

 

Further, 28 -day oral combined repeated dose toxicity studies with reproduction/developmental toxicity screening (OECD 422) are available for both read-across substances "basic aluminium chloride" and "zirconium acetate", respectively. There was a lack of developmental effects at the highest dose in both studies (1000 mg/kg bw/day in both studies, based on the respective test item). In analogy to the calculations on "fertility", see above, an oral NOAEL for the registered substance aluminium zirconium chloride hydroxide of 464 mg/kg bw/day for developmental effects (oral route) is taken forward (read-across based on Al moiety).

Testing in a second (rodent) species is waived based on the opinion that sufficient weight of evidence is available to conclude on the absence of pre-natal developmental toxicity in such species.This is based on the absence of metabolic conversion,similarities in toxicokinetic profiles of aluminium and zirconium, and the absence of developmental toxicity in rabbits with the substance in question as well as the existence of several negative developmental toxicity studies with various aluminium substances.


Justification for selection of Effect on developmental toxicity: via oral route:
NOAEL calculated based on Al content, using the NOAEL for developmental effects in an combined 28-day oral toxicity study with reproduction/developmental screening for the read-across substance basic aluminium chloride.

Justification for selection of Effect on developmental toxicity: via dermal route:
Key study with comparable substance aluminium zirconium chloride hydroxide glycinate (“ZAG”).

Justification for classification or non-classification

In reproductive and developmental 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 reproductive toxicity (effects on fertility or development).