Registration Dossier

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

71.1 mg/m³

Most sensitive endpoint:

neurotoxicity

Overall assessment factor (AF):

12.5

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

Hazard assessment conclusion:

no hazard identified

1. Introduction:

In this chapter, all the endpoints from Aluminium ammonium (bis) sulfate are re-examined and analyzed in order to establish a DNEL (s)/DMEL (s) for each one of them if possible. The followed method is that proposed in the guidance for the implementation of Reach (Chapter R.8: Characterisation of dose (concentration)-response for human health, May 2008)

2. Classification in the Annex VI of CLP Regulation (Regulation (EC) N°1272/2008)

Aluminium ammonium (bis) sulfate is not classified according to the Directive 67/548/EC and the CLP Regulation..

3. DNELs/DMELs derivation according to the toxicological profile of Aluminium ammonium (bis) sulfate

Inhalation exposure was the most appropriate route for assessing occupational risk in workers. Dermal exposure is not considered as a relevant route of exposure since Aluminium ammonium (bis) sulfate is not likely to be systematically absorbed by dermal route (see §7.1).

Neither indications of carcinogenic nor reprotoxic potential were observed or expected. Tests assessing the mutagenic potential of Aluminium ammonium (bis)sulfatein vitroandin vivoprovided no evidence of mutagenic or genotoxic activity.

No acute toxicity hazard has been identified and no peak exposure has been predicted for Aluminium ammonium (bis)sulfate, therefore the long-term DNEL by inhalation route ensure a sufficient level of protection. No DNEL_acutefor inhalation route has been derived.

Calculation of long-term DNEL by inhalation for systemic effects for Aluminium / Worker

The concentration descriptor has been obtained from the combined toxicity study (OECD 426/452) by oral route (see § 7.9.1). Granulometry on the powder of Aluminium ammonium (bis)sulfate showed no detectable particles in the alveolar fraction and a very low percentage of total particulates in the inhalable fraction (<100 µm). These particles are expected to be dissolved by the mucus from the respiratory tract in order to be swalled. Consequently the toxicity by inhalation is warranted due to the potential for oral toxicity and no uncertainty factor is considered for the absorption between the oral route and the inhalation.

Under the test conditions of the chronic neurotoxicity study using Aluminium citrate (considered as a worst-case relevant aluminium salt), neuromuscular effects were observed on male and female rats. The NOAEL in this study is 30 mg Aluminium/kg bw/d.

The following Table 3.1 indicates the inhalation DNEL-long term for systemic effects calculation.

Table 3.1:Calculation of long-term DNEL by inhalation route for systemic effects

Worker	Long-term DNEL / inhalation / systemic effects
*Step a : determination of the critical dose*
Key study	Combined study OECD 426/452, K2 (read-across)
Relevant dose descriptor	NOAEL = 30 mg Al/kg bw/d (rat, oral) for neuromuscular effects (females and males)
*Step b : Correct starting point – factor for uncertainties*
Differences in absorption depending on route of exposure (route-route extrapolation, human/animal)	1 (oral absorption for aluminium sulfate /absorption by inhalation)
Modification for exposure (experiment in animal and human)	1/0.38 (standard respiratory volume animal/human)
Modification for the respiratory volume	6.7/10 (respiratory rate difference under standard conditions and under conditions of light activity for 8 hours)
Correct starting point = relevant dose descriptor / overall factor for uncertainties	52.9 mg Al/m³
*Step c : assessment factors*
Interspecies differences - Differences in metabolic rate per b.w. (allometric scaling) - Remaining differences	- (Not applicable) 2.5
Intraspecies differences	5 (worker)
Duration extrapolation (sub-acute/sub-chronic/chronic)	1 (one-year repeated dose toxicity study)
Issues related to dose-response	1
Quality of the whole database	1
Overall assessment factor	12.5
DNEL calculation	4.23 mg Al/m³
DNEL calculation	71.1 mg salt/m³*

*Molecular Weight_salt=906.6 at 20°C

The inhalation DNEL long-term for systemic effects is 71.1 mg salt/m3in the worker. This value corresponds to an exposure of 4.23 mgAl/m3 which is already covered by the indicative occupationnal exposure level (IOEL) of 2 mg Al/m³used in many European countries.