Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Aluminium chloride, anhydrous, is classified as corrosive to the skin (harmonized classification as Skin Corr., category 1B, according to Annex VI of Regulation (EC) No 1272/2008), which is why the prevailing health effect upon dermal and inhalative exposure is considered to be local corrosion/irritation of the skin and the mucous membranes.

Since AlCl3anhydrous cannot be tested as a dust aerosol (as demonstrated by a technical trial described in IUCLID chapter 7.5.2; as an attachment to the RSS of the 90-day inhalation study), an aqueous solution of (Al(H2O)6)3+3Cl-(AlCl3hexahydrate) has been tested in a 90-day inhalation study in rats as it most likely represents the substance that is formed when anhydrous AlCl3reaches the humid environment of the respiratory tract. The study demonstrates that an aqueous aerosol of inhaled AlCl3hexahydrate is corrosive to the upper respiratory tract and leads to inflammatory responses in the lung even at low concentrations. It can be stated that an intrinsic hazard of anhydrous AlCl3is its corrosivity to the respiratory tract. However, the LOAEL and NOAEL defined in the study report are not suitable to derive a DNEL which can be used for worker risk assessment of the exposure scenarios reported for the following reasons:

There are no spray uses with anhydrous AlCl3in aqueous solution and the risk of worker exposure to liquid aerosol is not given. The only form in which AlCl3anhydrous is present in the workplace with possible worker exposure is given via solid particles. These, however, are not able to penetrate the deep lung in the way a well-defined liquid aerosol is.

The importance of taking into account the form of a substance during its actual use is also emphasized in chapter R.14.4.1 of ECHA´s guidance on information requirements and chemical safety assessment, chapter R.14: occupational exposure assessment:

“The physicochemical properties of the substance and its form during use are to be taken into account. Depending on the case, the expected exposure may benefit from being quantified to support the argumentation. […] Also, the particle size distribution of the airborne fraction released during use may be different from the distribution measured from stored samples of the manufactured material or from the test material in the toxicity study.”[ECHA, 2016]

The particle size analysis performed during the inhalation study demonstrated that the aerosols were highly respirable for the rats and a very high proportion of the aerosol particles reached the lungs (MMAD between 0.9 and 1.39 µm with GSDs <3).

The values for particle size of anhydrous aluminium chloride obtained in the granulometry measurements [BASF AG, 2007] (see IUCLID chapter 4.5) can be converted to MMAD values by applying the formula of Raabe [Raabe, 1976]. 

The following table represents the particle size distribution for aluminium chloride anhydrous as well as corresponding aerodynamic diameter

  Table 1: Particle size distribution of anhydrous aluminium chloride

Distribution

Particle size

Corresponding MMAD

45 %

< 100 µm

 

< 156.2 µm

7 %

< 10 µm

 

< 15.62 µm

3 %

< 4 µm

 

< 6.25 µm

 

The particle size distribution shows, that only about 3 % of anhydrous AlCl3particles are in the range of respirable particles (MMAD ≤ 10 µm). This is a rather conservative approach, as particle size distribution has been determined under nitrogen atmosphere. Under realistic conditions, the highly hygroscopic particles will rapidly increase in size due to the reaction with air humidity and subsequent agglomeration. This has been shown by the technical trial which demonstrated that it is impossible to obtain a stable dust aerosol of anhydrousaluminium chloride due to its hygroscopic properties. In addition to that trial, it has to be stated that the ambient air in the manufacturing plant is highly humid due to the water-cooling systems of the reactors.

 

Because of the architecture of the respiratory tract, which modulates the airflow, particle size is a critical factor in determining the region of the respiratory tract in which a particle will be deposited. The efficiency of particle deposition in various regions of the respiratory tract depends mainly on particle size [Klaassen, 2018].

Particles deposit by impaction, interception, sedimentation, diffusion, and electrostatic deposition (for positively charged particles only). Impaction is the dominant way of deposition in the upper respiratory tract and large proximal airways where the airflow is faster than in the small distal airways because the cumulative diameter is smaller in the proximal airways.

In humans, most particles bigger than 10 µm are deposited in the nose or oral pharynx and cannot penetrate tissues distal to the larynx. For 0.2 to 10 µm particles, impaction continues to be the mechanism of deposition in the first generations of the tracheobronchial region [Klaassen, 2018].

Even after inhalation, aerosol particles of hygroscopic substances change towards bigger size due to the humid properties of the human respiratory system. It´s one of the responsibilities of the upper respiratory tract (especially the nose) to humidify the inhaled air and subsequently, hygroscopic growth of particles leads to a shift in deposition pattern towards impaction and sedimentation [Haddrell et al., 2017].

In addition to that, nasal passages effectively absorb water-soluble and reactive compounds like anhydrous aluminium chloride.

For all the reasons stated above, it is highly unlikely that inhaled particles of anhydrous AlCl3can reach the lower respiratory tract and elicit an exposure pattern comparable to the situation given in the 90-day inhalation study.

The importance of particle size for the assessment of inhalation exposure is also described in chapter R.14.2.1 of ECHA´s guidance on information requirements and chemical safety assessment, chapter R.14: occupational exposure assessment:

“When assessing the exposure arising from aerosols […], some considerations may need to be taken into account such as the aerodynamic particle size. […] Particle size is important because, firstly it determines the uptake, as some particles will not be inhaled due to their size.[…] However, for particle having an effect by accumulation in a specific area of the respiratory tract (may be regarded as local effects), only the particles within a certain size-range may be of interest in the exposure assessment.”[ECHA, 2016]

However, the 90-day inhalation study describes the intrinsic hazard of anhydrous AlCl3to induce local corrosion after inhalation. Once inhaled, AlCl3particles are mainly deposited in the upper respiratory tract. AlCl3reacts violently with water to form the hexahydrate which then undergoes hydrolyzation. Hydrogen chloride is released and, over time, aluminium hydroxide precipitates [Hollemann, Wiberg, 2007]:

AlCl3+ 6 H2Oà[Al(H2O)6]3+ + 3 Cl-

[Al(H2O)6]Cl3Al(OH)3+ 3 HCl+ 3 H2O

It is reasonable that the release of hydrogen chloride is responsible for the corrosive properties of anhydrous aluminium chloride in the respiratory tract.

The risk minimization measurements therefore are designed to prevent the substance from being inhaled and in contact with the skin where the inhalation and dermal exposure to dust particles or dermal exposure to droplets of the substance in solution cannot be completely ruled out.

 

For all the reasons stated above and with respect to the exposure profile of anhydrous aluminium chloride, the risk assessment has been performed qualitatively. In the following section, the technical measures and personal protection equipment in place have been described in detail for every single use, demonstrating safe handling of the substance.

 

References:

ECHA (2016). Guidance on Information Requirements and Chemical Safety Assessment Chapter R.14: Occupational exposure assessment, version 3.0

BASF AG (2007). Characterisation and particle size distribution of Aluminiumchlorid wasserfrei gemahlen.(PBG 10000464)11

Raabe, Otto G. (1976). Aerosol aerodynamic size conventions for inertial sampler calibration. Journal of the Air Pollution Control Association 26 (9)

BASF SE (2019). Ermittlung und Bestimmung der inhalativen Exposition gegenüber Gefahrstoffen nach TRGS 402. DE/LU/B516/0032/20

Klaassen, Curtis (2018).Casarett & Doulls Toxicology - The Basic Science of Poisons.McGraw-Hill Education Ltd; 9thedition

Haddrell, Allen E. et al. (2017). Pulmonary aerosol delivery and the importance of growth dynamics.Therapeutic delivery 8 (12), 1051-1061

Hollemann, Arnold F., Wiberg, Nils (2007). Lehrbuch der Anorganischen Chemie.102ndedition.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default assessment factor according to ECHA Guidance Chapter R.8.
AF for differences in duration of exposure:
1
Justification:
As the starting point is derived from an adequate chronic toxicity study in rats, no assessment factor for duration extrapolation is needed (in accordance with ECHA Guidance Chapter R.8).
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling from rat to human according to ECHA Guidance Chapter R.8.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor according to ECHA Guidance Chapter R.8.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population according to ECHA Guidance Chapter R.8.
AF for the quality of the whole database:
1
Justification:
Default assessment factor according to ECHA Guidance Chapter R.8.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties anticipated.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

As no reliable oral repeated dose data are available for aluminium chloride, anhydrous, the systemic oral DNELs for general population were derived on the basis of systemic effects of aluminium citrate observed in an oral developmental neurotoxicity study with extended exposure of the pups of up to one year of age (ToxTest, 2010; see chapter 7.8.2 of the IUCLID). The conservative NOAEL of 30 mg Al/kg bw (corresponding to 150 mg AlCl3/kg bw) with regard to neuromuscular effects in the offspring of dams treated with aluminium citrate in the drinking water was employed as a point of departure.