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.

Link to relevant study records

Reference

Reference 1

Endpoint:

multi-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Well-presented study, with relevant measurement of chemical concentrations

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.35 (Two-Generation Reproduction Toxicity Test)

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

other: Dobra Voda

Sex:

female

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

The chronic toxicity was studied in a reproduction experiment on white mice. Ten mice received aluminium chloride in their drinking water, receiving on the average 19.3 mg Al/kg./day. They were compared with to control mice. The experiment lasted 180 to 390 days, during which weight increases, number of litters, and number of off-spring were recorded.

Details on mating procedure:

The weanlings were treated from 4 weeks of age like their parents. At the end of the experiment the animals were killed by decapitation, the blood was examined for changes in the red cell count, and the liver, spleen, and kidneys were examined histologically.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Exposure period: 180 - 390 d (weanlings were treated from 4.week of age like parents)

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0; 19.3 mg/kg/d (doses expressed in terms of Al)
Basis:

No. of animals per sex per dose:

10

Control animals:

yes

Positive control:

No

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: daily




WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations:daily

Oestrous cyclicity (parental animals):

not examined

Sperm parameters (parental animals):

not examined

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no


PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring: yes
There were no significant differences in the numbers of litters or off-spring between the treated and control mice. 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

GROSS EXAMINATION OF DEAD PUPS:no

Postmortem examinations (parental animals):

The weanlings were treated from 4 weeks of age like their parents. At the end of the experiment the animals were killed by decapitation, the blood was examined for changes in the red cell count, and the liver, spleen, and kidneys were examined histologically.

Postmortem examinations (offspring):

The weanlings were treated from 4 weeks of age like their parents. At the end of the experiment the animals were killed by decapitation, the blood was examined for changes in the red cell count, and the liver, spleen, and kidneys were examined histologically.

Statistics:

An analysis of variance (Weber, 1964) established that, under the conditions of our experiment, weight variations could be accounted for by aluminium uptake (p < 0.001). The differences in the course of weight plots for successive generations and litters were also statistically Significant (p <0.01).

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Other effects:

effects observed, treatment-related

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

There were no significant differences in the numbers of litters or off-spring between the treated and control mice.
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 . An analysis of variance , under the conditions of this experiment, weight variations could be accounted for by aluminium uptake (p < 0.001).
The differences in the course of weight plots for successive generations and litters were also statistically Significant (p <0.01

The erythrocyte counts and haemoglobin levels in the first and last generations did not differ significantly from those in the controls; and no pathological changes could be found in the tissues examined.

Dose descriptor:

NOAEL

Effect level:

310 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects: The subsequent litters manifested a very marked growth retardation, as did those of the third generation

Remarks on result:

other: Generation: F3 (migrated information)

Clinical signs:

effects observed, treatment-related

Mortality / viability:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings:

effects observed, treatment-related

There were no significant differences in the numbers of litters or off-spring between the treated and control mice.
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 . An analysis of variance , under the conditions of this experiment, weight variations could be accounted for by aluminium uptake (p < 0.001).
The differences in the course of weight plots for successive generations and litters were also statistically Significant (p <0.01

The erythrocyte counts and haemoglobin levels in the first and last generations did not differ significantly from those in the controls; and no pathological changes could be found in the tissues examined.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

310 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

310 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Reproductive effects observed:

not specified

There were no significant differences in the numbers of
litters or off-spring between the treated and control
mice. 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. An analysis of variance
established that, under the conditions of our experiment,
weight variations could be accounted for by aluminium
uptake (P < 0.001). The differences in the course of weight
plots for successive generations and litters were also
statistically significant (P < 0.01).
The erythrocyte counts and haemoglobin levels in the
first and last generations did not differ significantly
from those in the controls; and no pathological changes
could be found in the tissues examined.

Conclusions:

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.

Reference 2

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliable with restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Route of administration:

inhalation: dust

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: Wright dust feed mechanism.

Details on exposure:

Groups of rats and guinea pigs were exposed, by inhalation, to 0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate (ACH) for six months to study the effects of a common component of antiperspirants. Similar groups of animals of both species exposed to clean air served as controls. The ACH was generated as a particulate dust using a Wright dust feed mechanism. After six months of exposure, animals were sacrificed.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 months

Frequency of treatment:

5 day/ week, 6 hours/day

Remarks:

Doses / Concentrations:
0.25, 2.5, and 25 mg/m3 of aluminum chlorhydrate
Basis:
nominal conc.

No. of animals per sex per dose:

na

Control animals:

yes

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule:5day/week, 6 hour/day


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:5day/week, 6 hour/day

BODY WEIGHT: Yes
- Time schedule for examinations:5day/week, 6 hour/day

Clinical signs:

effects observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Decreases in body weight were seen in rats exposed to 25 mg Al/m3

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Decreases in body weight were seen in rats exposed to 25 mg Al/m3

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not examined

Reproductive function: oestrous cycle:

no effects observed

Description (incidence and severity):

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 aluminium sulphate.

Reproductive function: sperm measures:

no effects observed

Description (incidence and severity):

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 aluminium sulphate.

Reproductive performance:

no effects observed

Description (incidence and severity):

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 aluminium sulphate.

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 aluminium sulphate
Decreases in body weight were seen in rats exposed to 25 mg/m3 of ACH. Marked increases in lung weights and significant increases in lung to body weight ratios were seen in rats and guinea pigs exposed to 25 mg/m3 of ACH. The lungs of all rats and guinea pigs showed significant dose-related increases in aluminum accumulation when exposed to either 0.25, 2.5, or 25 mg/m3 of ACH. The lungs of all rats and guinea pigs exposed to either 2.5 or 25 mg Al/m3 of ACH contained exposure-related granulomatous reactions characterized by giant vacuoled macrophages containing basophilic material in association with eosinophilic cellular debris.

Dose descriptor:

NOAEL

Effect level:

38.6 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: 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 as aluminum chlorhydrate or 38.6 mg/m3 as aluminium sulphate for 6 months

Remarks on result:

other: Generation: adult Fischer 344 rats and Hartley guinea pigs e (migrated information)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Reproductive effects observed:

not specified

Conclusions:

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 as aluminum chlorhydrate for 6 months .

Executive summary:

Groups of rats and guinea pigs were exposed, by inhalation, to 0.25, 2.5, and 25 mg Al/m3 of aluminum chlorhydrate (ACH) for six months to study the effects of a common component of antiperspirants. Similar groups of animals of both species exposed to clean air served as controls. The ACH was generated as a particulate dust using a Wright dust feed mechanism. After six months of exposure, animals were sacrificed. Decreases in body weight were seen in rats exposed to 25 mg Al/m3 of ACH. Marked increases in lung weights and significant increases in lung to body weight ratios were seen in rats and guinea pigs exposed to 25 mgAl/m3 of ACH. The lungs of all rats and guinea pigs showed significant dose-related increases in aluminum accumulation when exposed to either 0.25, 2.5, or 25 mgAl/m3 of ACH. The lungs of all rats and guinea pigs exposed to either 2.5 or 25 mgAl/m3 of ACH contained exposure-related granulomatous reactions characterized by giant vacuoled macrophages containing basophilic material in association with eosinophilic cellular debris.

 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

310 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

38.6 mg/m³

Study duration:

chronic

Species:

rat

Effect on fertility: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2.48 mg/kg bw/day

Study duration:

chronic

Species:

mouse

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 mouse is 80g (60-100g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg

corrected dermal NOAEL= oral NOAEL

310 mg/kg bw/day 0.008 kg =

NOAELmouse 2.48 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).

.

Short description of key information:
There are conclusive but not suffcient data for the classification of substance Aluminium sulphate with regard to reproduction.
It is concluded that the substance Aluminium sulphate does not meet the criteria to be classified for human health hazards for Reproductive toxicity
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.

Justification for selection of Effect on fertility via dermal route:
For dermal exposure we taken that:
-the average weight of mouse is 80g (60-100g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg
corrected dermal NOAEL= oral NOAEL
310 mg/kg bw/day 0.008 kg =
NOAELmouse 2.48 mg/kg bw/day

Effects on developmental toxicity

Description of key information

There are conclusive but not suffcient data for the classification of substance Aluminium sulphate with regard to Developmental toxicity / teratogenicity
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).

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Reliable without restrictions. Well-presented study, with relevant measurement of chemical concentrations

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 83-3 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Limit test:

no

Species:

mouse

Strain:

CBA

Route of administration:

other: oral: drinking water and intraperitoneally

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Pregnant mice were injected intraperitoneally with 200mg/kg aluminum-sulfate or saline from days 10 to 13 of gestation inclusive.
A second group of pregnant mice was given aluminum-sulfate at 750 milligrams/liter as their sole drinking water from days 10 to 17 of gestation inclusive.


DIET PREPARATION
- Rate of preparation of diet (frequency): daily
- Mixing appropriate amounts with (Type of food): not applicable
- Storage temperature of food: ambient

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

All doses were administered once daily by gastric intubation, on gestation days 10-17

Frequency of treatment:

daily

Duration of test:

22 weeks

Remarks:

Doses / Concentrations:
750 mg/l as their sole drinking water from days 10 to 17 of gestation inclusive.
Basis:
nominal in water

Remarks:

Doses / Concentrations:
200mg/kg aluminum-sulfate or saline from days 10 to 13 of gestation inclusive
Basis:
other: intraperitoneally

No. of animals per sex per dose:

number not reported

Control animals:

yes, concurrent vehicle

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily



DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
Offspring were sacrificed at ages ranging from 3 to 44 weeks for determination of choline-acetyltransferase activity.
For behavioral and developmental studies, pups were cross fostered on postnatal day one.
Pups were tested for slow righting, cliff aversion, forelimb grasping, pole grasping, climbing on a wire mesh, and eye opening. At 10 weeks, male mice were tested in an eight arm radial maze. At 22 weeks, adult activity tested were carried out.


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes .
- Time schedule for examinations: daily


POST-MORTEM EXAMINATIONS: Yes

- Organs examined: brain, The cholinergic system, as evaluated by the activity of choline acetyltransferase (ChAT), was affected differentially in different regions of the brain, and still showed significant effects in the adult.

Fetal examinations:

- External examinations: Yes:
- Soft tissue examinations: No data
- Skeletal examinations: Yes:
- Head examinations: Yes:
All foetuses were checked for external malformations, the foetuses were subjected to visceral examination (including sectioning of the head) and examined for skeletal changes

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Growth rate and psychomotor maturation in the pre-weaning mouse were affected in the intraperitoneal series only, showing a marked post-natal maternal effect.

Dose descriptor:

LOAEL

Effect level:

276.8 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day (nominal)

Based on:

test mat.

Remarks:

injected intraperitoneally

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
retarded fetal body weight and development in high dose group. No evidence of teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

 The effect on prenatal exposure to aluminum-sulfate (10043013) on brain biochemistry and behavioral development were investigated in CBA-mice. Long term effects on growth, behavior, and the cholinergic system were reported. Pregnant mice were injected intraperitoneally with 200 mg/kg aluminum-sulfate or saline from days 10 to 13 of gestation inclusive. A second group of pregnant mice was given aluminum-sulfate at 750 milligrams/liter as their sole drinking water from days ten to 17 of gestation inclusive. Offspring were sacrificed at ages ranging from 3 to 44 weeks for determination of choline-acetyltransferase activity. For behavioral and developmental studies, pups were cross fostered on postnatal day one. Pups were tested for slow righting, cliff aversion, forelimb grasping, pole grasping, climbing on a wire mesh, andeyeopening. At 10 weeks, male mice were tested in an eight arm radial maze. At 22 weeks, adult activity tested were carried out. The cholinergic system, as evaluated by the activity of choline-acetyltransferase, was affected differentially in different regions of the brain and still showed significant effects in the adult. Differences between the intraperitoneal and oral series in the magnitude of effect seen in the regions of the brain probably reflect differences in the effective level of exposure. Growth rate and psychomotor maturation in the preweaning mouse were affected in the intraperitoneal series only, showing a marked postnatal maternal effect.

Conclusions:

Lowest Adverse Effect Level (LOAEL) for Aluminium sulphate of 276.8 mg/kg/day ( in drinking water ) were established, based on effects seen in growth rate and psychomotor maturation in the preweaning mouse, recorded effects in mice included impaired performance of reflexes and simple behaviours (righting reflex, grasping, negative geotaxis, rod climbing).

Executive summary:

Pregnant mice were injected intraperitoneally with 200 mg/kg aluminum-sulfate or saline fromdays 10 to13 of gestation inclusive. A second group of pregnant mice was givenaluminum-sulfate at 750 milligrams/liter as their sole drinking water fromdays10to 17 of gestation inclusive. Offspring were sacrificed at ages ranging from 3 to 44 weeks for determination of choline-acetyltransferaseactivity.

For behavioral and developmental studies, pups were cross fostered on postnatal day one. Pups were tested for slow righting, cliff aversion, forelimb grasping, pole grasping, climbing on a wire mesh, and eye opening. At 10 weeks, male mice were tested in an eight arm radial maze. At 22 weeks, adult activity tested were carried out.

The cholinergic system, as evaluated by the activity of choline-acetyltransferase, was affected differentially in different regions of the brain and still showed significant effects in the adult. Differences between the intraperitoneal and oral series in the magnitude of effect seen in the regions of the brain probably reflect differences in the effective level of exposure.Growth rate and psychomotor maturation in the preweaning mouse were affected in the intraperitoneal series only, showing a marked postnatal maternal effect.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

276.8 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEC

12 mg/m³

Study duration:

chronic

Species:

mouse

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

2.21 mg/kg bw/day

Study duration:

chronic

Species:

mouse

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 mouse is 80 g (60-100g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg

corrected dermal LOAEL= oral LOAEL

276.8 mg/kg bw/day 0.008 kg =

LOAELmouse 2.21 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.

LOAELmouse             

 276.8 mg/kg bw/day

÷1.15m3/kgbw

÷20m3/mouse

LOAECmouse     12 mg/m3

Justification for selection of Effect on developmental toxicity: via inhalation route:
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.
LOAELmouse             
 276.8 mg/kg bw/day
÷1.15m3/kgbw
÷20m3/mouse
LOAECmouse     12 mg/m3

Justification for selection of Effect on developmental toxicity: via dermal route:
For dermal exposure we taken that:
-the average weight of mouse is 80 g (60-100g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.008 kg
corrected dermal LOAEL= oral LOAEL
276.8 mg/kg bw/day 0.008 kg =
LOAELmouse 2.21 mg/kg bw/day

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 5.4., 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