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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
269 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
269 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
1
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

Workers - Hazard for the eyes

Additional information - workers

Long-term DNEL Derivations (worker) for local and systemic inhalation exposure:

 

Substance : read-across from Aluminium hydroxide

 

Key Studies for Dose Descriptor

 

Pauluhn (2009a) is considered the most adequate study from which to obtain a dose descriptor for the basis of a DNEL for repeated dose toxicity (inhalation, local effect) for aluminium hydroxide.

The LOAEC from Pauluhn (2009a), a subacute inhalation study, is 28 mg/m3 for a critical effect of focal septal collagen and a persistent increase in PMNs. The NOAEC from Pauluhn (2009a) is 3 mg/m3. There were no dose levels in the study between 3 and 28 mg/m3.The calculation for Pauluhn (2009a) was provided earlier.

For Alag, due to the granulometry and the chemical composition, the derived LOAEC is 50008 mg/m3, and the derived NOAEL is 5358 mg/m3 (see section 7.5).

Long-term DNEL derivation for Alag based on Pauluhn et al. (2009) study :

KEY REFERENCE: Pauluhn J. Pulmonary toxicity and fate of agglomerated 10 and 40 nm aluminium oxyhydroxides following 4-week inhalation exposure of rats: Toxic effects are determined by agglomerated, not primary particle size. Toxicol Sci 2009; 109(1): 152-167.

TEST ANIMAL:

Wistar rats (male)

TEST SUBSTANCE:

Aluminium oxyhydroxide (AlO(OH))

EXPOSURE ROUTE/MEDIUM/ CONCENTRATION/DURATION

Inhalation/ agglomerates of nanosized particulates AlO(OH)-40 (MMAD = 0.6 μm) and AlO(OH)-10 (MMAD = 1.7μm)/ 0, 0.4, 3 and 28 mg/m3 AlO(OH)/ 6 hrs per day, 5 days per week, 4 weeks [subacute duration]

CRITICAL EFFECT:

Focal septal collagen that did not regress (but did not progress) post-exposure; persistent elevation of polymorphonuclear neutrophilic granulocytes.

MODE OF ACTION:

 Threshold (portal of entry - overload)

DOSE-DESCRIPTOR:

5358

mg/m3(LOAEC)

MODIFYING FACTORS:

 

 

Daily exposure duration

  experiment)

6

6 hours per day, 5 days per week.     

Daily exposure duration (target population)

8

8 hours per day, 5 days per week

Inhalatory volume ( experiment)

6.7

Inhalatory volume (rat): 6.7 m3(8h).

Inhalatory volume (target population)

10

Inhalatory volume (human): 10 m3(8h)

Bioavailability differences between test and target species:

1

No evidence suggesting that there would be a difference between animal species with respect to actual bioavailability.

TOTAL MODIFYING FACTOR:

0.503

 

Corrected Starting Point:

2695

mg/m3

ASSESSMENT FACTORS

 

 

Interspecies:

1

Allometric scaling not necessary as adjustment for inhalation volume has already been done; mode of action is a portal-of-entry effect (overload); scientific evidence suggests a greater susceptibility to overload in rats (Pauluhn, 2010; Jarabek et al., 2005) therefore a factor of 2.5 for remaining uncertainty (the default in the ECHA Guidance) was not considered appropriate.

Intraspecies:

5

Default for workers (ECHA Guidance, Chapter R8, p34)

Duration of exposure:

1

Local threshold effect; further adjustment for time-scaling is not considered justified.

Dose-response extrapolation:

2

Based on a LOAEC; but a suite of very sensitive endpoints were measured in this study; the critical effect was not severe; the inflammatory effects showed reversibility and the focal septal collagen did not show progression post-exposure.

Adequacy of database:

1

The key study was GLP with 3 months of follow-up; sufficient to see the reversibility of observed effects.

TOTAL ASSESSMENT FACTOR:

10

 

 

269

mg/m3substance, daily 8 hour TWA (respirable)

Ratio of inhalation bioavailabilities – test: target

1

 

1

 

Long-term DNEL:

269 

mg/m3Substance, daily 8 hour TWA (respirable)

Short-term DNEL Derivation (worker and consumer):

According to the granulometry and the composition of the substance, the amount of the soluble fraction of aluminium species will be too low in the alveoli. Therefore, no short-term DNEL by inhalation can be reasonably derived for worker and consumer

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

General population is not supposed to be exposed to Alag, while processed. Some short term exposure by dermal or inhalation route could be expected at very low level when people are working for their own. Therefore no adverse effect could be expected in the general population.