Aluminium sulphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

White leghorn laying hens were fed diets containing 0, 0.15% (187.5mg/kg bw Aluminium sulphate) or 0.3% aluminium (375 mg/kg bw Aluminium sulphate) for 17 weeks. The LOAEL was based on significantly depressed fertility and chick body weight at 0.15% and these effects plus significantly reduced total egg production and feed consumption at 0.3% aluminium. Egg hatchability was unaffected.

Effect on fertility: via oral route

Dose descriptor:

NOAEL

310 mg/kg bw/day

Effect on fertility: via inhalation route

Dose descriptor:

NOAEC

38.6 mg/m³

Effect on fertility: via dermal route

Dose descriptor:

NOAEL

7.8 mg/kg bw/day

Additional information

Oral exposure:

The NOAEL (No Observed Adverse Effect Level) for effects on off-spring growth was 310 mg/kg/bw/day.

Growth was retarded and was dependent on the intake of aluminium, but the effect did not appear in the first generation or in the first litter. The subsequent litters manifested a very marked growth retardation, as did those of the third generation.

The NOAEL of 317 mg/kg/bw/day was based on.delay in vaginal opening. No effects on female fertility.delay in vaginal opening

The NOAEL of 633 mg/kg/bw/day was based on decreased forelimb grip strength, decreased pup body weight. No effects on female fertility.

There was a reduction of food consumption and maternal body weight gain during gestational days 7 -15 in the groups exposed to aluminium compared to the control group. There were no differences among the groups in the length of gestation, mean number of pups per litter, viability index, and pup body weight at birth.

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

corrected dermal NOAEL= oral NOAEL

310 mg/kg bw/day 0.025 kg =

NOAELrat 7.8 mg/kg bw/day

Inhalation exposure:

No histological changes were observed in reproductive tissues of Fischer 344 rats or Hartley guinea pigs exposed by inhalation to 6.1 mg Al/m3 or 38.6 mg/m3 as aluminum chlorhydrate for 6 months (Steinhagen et al. 1978).

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Short description of key information:
The NOAEL (No Observed Adverse Effect Level) for effects on off-spring growth was 310 mg/kg/bw/day.
Growth was retarded and was dependent on the intake of aluminium, but the effect did not appear in the first generation or in the first litter. The subsequent litters manifested a very marked growth retardation, as did those of the third generation.
The NOAEL of 317 mg/kg/bw/day was based on.delay in vaginal opening. No effects on female fertility.delay in vaginal opening
The NOAEL of 633 mg/kg/bw/day was based on decreased forelimb grip strength, decreased pup body weight. No effects on female fertility.
There was a reduction of food consumption and maternal body weight gain during gestational days 7 -15 in the groups exposed to aluminium compared to the control group. There were no differences among the groups in the length of gestation, mean number of pups per litter, viability index, and pup body weight at birth.

Effects on developmental toxicity

Description of key information

From the results presented in 7.8.2 (Developmental toxicity / teratogenicity), a definitive No Observed Adverse Effect Level (NOAEL) for Aluminium sulphate of 40 mg/kg/day (injected intraperitoneally) and Lowest Observed Adverse Effect Level (LOAEL) for Aluminium sulphate of 276.8 mg/kg/day ( in drinking water ) were established, based on effects seen in brain, behaviour of the offspring and the activity of choline acetyltransferase (ChAT), at 276.8  mg/kg/day.
Effects recorded in mice included impaired performance of reflexes and simple behaviours (righting reflex, grasping, negative geotaxis, rod climbing).

Effect on developmental toxicity: via oral route

Dose descriptor:

LOAEL

276.8 mg/kg bw/day

Effect on developmental toxicity: via inhalation route

Dose descriptor:

NOAEC

12 mg/m³

Effect on developmental toxicity: via dermal route

Dose descriptor:

LOAEL

6.9 mg/kg bw/day

Additional information

Oral exposure:

From the results presented in 7.8.2(Developmental toxicity / teratogenicity a Lowest Observed Adverse Effect Level (LOAEL)

for Aluminium sulphate of 276.8 mg/kg/day or 750 mg/l was established, based on effects seen in brain, behaviour of the offspring and the activity of choline acetyltransferase (ChAT), at 276.8 mg/kg/day. Effects recorded in mice included impaired performance of reflexes and simple behaviours (righting reflex, grasping, negative geotaxis, rod climbing)

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

corrected dermal LOAEL= oral LOAEL

276.8 mg/kg bw/day 0.025 kg =

LOAELrat 6.9 mg/kg bw/day

Inhalation exposure:

No studies were identified concerning the developmental effects of inhalation exposure to aluminum salts.

The oral dose for the mouse is converted to the corresponding air concentration using a standard breathing volume for the mouse (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m³), assuming 100 % absorption for both routes.

NOAELmouse             

 276.8 mg/kg bw/day

÷1.15m3/kgbw

÷20m3/mouse

NOAECmouse     12 mg/m3

Toxicity to reproduction: other studies

Additional information

This experiment in study of Wisser (1990) was conducted to evaluate the effectof aluminum exposure on productivity, fertility and hatchability.

 Bythesecond week of treatment, 0.30% added dietary aluminum significantly decreased egg output. However, afterthe initial drop in production, hens fed this diet maintained consistent output and did not show signs ofinduced molt. Overall, production was not affected by0.15% added dietary aluminum but was reduced significantly by 0.30% aluminum. Feed consumption wassignificantly reduced by 0.30% added dietary aluminum.

There was no change in egg weight associated withdietary aluminum, which is consistent with a preliminary study. However, an unexpected significant increasein percent shell occurred in both groups receiving addedaluminum.

The addition of 0.30% dietary aluminum slightly but significantly lowered fertility. However, percent hatchability showed no significant changes.

Justification for classification or non-classification

Based on the hazard assessmentof aluminium sulphate in section 2.1 and 2.2.in IUCLID 5.2., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

 

Directive 67/548

Toxicity to reproduction/development Repr. Cat. 1; R61 May cause harm to the unborn child. Repr. Cat. 2; R61 May cause harm to the unborn child. Repr. Cat. 3; R63 Possible risk of harm to the unborn child. Toxicity to reproduction/fertility  Repr. Cat. 1; R60 May impair fertility. Repr. Cat. 2; R60 May impair fertility. Repr. Cat. 3; R62 Possible risk of impaired fertility

CLP

Reproductive toxicity Repr. 1A Repr. 1B Repr. 2 H360: May damage fertility or the unborn child <state specific effect if known > <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H361: Suspected of damaging fertility or the unborn child <state specific effect if known> <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

It is concluded that the substance aluminium sulphate does not meet the criteria to be classified for human health hazards for Reproductive toxicity