Aluminium sulphate

Toxicity to reproduction

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1966

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium chloride

EC Number:

231-208-1

EC Name:

Aluminium chloride

Cas Number:

7446-70-0

IUPAC Name:

aluminum trichloride

Details on test material:

Name of test material:others-aluminium chloride
Name of test material: Aluminium chloride
- CAS Number: 7446-70-0
- EC Number: 231-208-1
- Molecular formula (if other than submission substance): AlCl3
- Molecular weight (if other than submission substance): 133.34 g/mol
- Smiles notation (if other than submission substance): Cl[Al](Cl)Cl
- InChl (if other than submission substance):= InChI=1/Al.3ClH/h;3*1H/q+3;;;/p-3
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type:inorganic
- Physical state:solid
- Appearance: white or pale yellow solid, hygroscopic
- Density – 2.48 g/cm3
- Melting point- 192.4 °C
- Solubility in water - 43.9 g/100 ml (0 °C), 44.9 g/100 ml (10 °C), 45.8 g/100 ml (20 °C),46.6 g/100 ml (30 °C), 47.3 g/100 ml (40 °C), 48.1 g/100 ml (60 °C), 48.6 g/100 ml (80 °C), 49 g/100 ml (100 °C
- Solubility: soluble in hydrogen chloride, ethanol, chloroform, carbon tetrachloride slightly soluble in benzene

Test animals

Species:

mouse

Strain:

other: Dobra Voda

Sex:

female

Administration / exposure

Route of administration:

oral: drinking water

Type of inhalation exposure (if applicable):

whole body

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.

Duration of treatment / exposure:

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

Frequency of treatment:

daily

Doses / concentrations

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

Examinations

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).

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

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.

Effect levels (P0)

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)

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

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.

Effect levels (F1)

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'

Results: F2 generation

Effect levels (F2)

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'

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

RS-Freetext:
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.

Applicant's summary and conclusion

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.