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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: I.p. administration is generally not recommended.

Data source

Reference
Reference Type:
publication
Title:
Assessment of genotoxicity of aluminium acetate in bone marrow, male germ cells and fetal liver cells of Swiss albino mice
Author:
D'Souza, Sr.P. et al.
Year:
2014
Bibliographic source:
Mutat Res Genet Toxicol Environ Mutagen 766:16 - 22

Materials and methods

Principles of method if other than guideline:
A sperm-abnormality assay was performed by treating male mice with a single dose and determining the frequency of abnormalities in sperm cells harvested 5 weeks later.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): aluminium acetate, C₆H₉AlO₆
- Physical state: white, light hygroscopic powder
- Analytical purity: no data
- Lot/batch No.: 1049

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: departmental animal house of the Department of Applied Zoology, Mangalore University, Mangalagangothri, India
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 25 ± 2 g
- Diet: commercial food pellets (Amrutha feeds, Bangaloer, India), ad libitum
- Water: unspecified source, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Remarks:
double distilled
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
single treatment
Frequency of treatment:
single treatment
Duration of test:
5 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 100 and 150 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5 males
Control animals:
yes, concurrent vehicle
Details on study design:
Eight-week-old virgin male mice were used. Post-treatment sampling was done after five weeks considering the duration required for spermatogenesis, and for sperm reaching the cauda epididymis. Sperm suspensions were made in phosphate-buffered saline (pH7.2) from both caudae and stained with 1% eosin-Y.

A total of 2000 sperm per animal were scored to determine the frequency of sperm abnormalities, which include hookless, amorphous, banana-shaped, folded, double-headed and double-tailed. The frequency of abnormal sperm was expressed as percentage, calculated with the formula: [number of abnormal sperm - total number of normal and abnormal sperm scored] × 100. In addition, testes weight and sperm count per epididymis were determined.

The positive control was 0.2 mL cyclophosphamide via intraperitoneal injection (50 mg/kg bw).
Statistics:
Statistical analysis of the data was performed by means of the paired t-test. A P-value < 0.05 was considered to correspond with statistical significance.

Results and discussion

Effect levels

Dose descriptor:
LOAEL
Effect level:
50 other: mg/kg bw
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Increased percentage abnormal sperm

Observed effects

Aluminium acetate induced a dose-dependent and statistically significant increase in the frequency of abnormal sperm when compared with the control (see Table 1 under 'Any other information on results incl. tables'). There was a dose-dependent reduction in sperm count, which was significant in the 100 and 150 mg/kg bw groups. The body and testis weights were not significantly affected at any of the doses tested. The positive control cyclophosphamide induced a significant increase in sperm abnormalities and a significant reduction in sperm count (P < 0.001).

Any other information on results incl. tables

Table 1: Frequency of different types of abnormal sperm induced in Swiss albino mice after five weeks of treatment with aluminium acetate*

Dose (mg/kg bw)

A

B

H

F

DH

DT

Total abnormal

% abnormal sperm ± SEM

 Control

33

8

31

26

2

7

107

1.07 ± 0.26

 50 CP

182

43

149

100

12

25

511

5.11 ± 0.59c

 50 Al

89

28

46

36

6

12

217

2.17 ± 0.31a

 100 Al

115

62

48

57

5

25

312

3.12 ± 0.76b

 150 Al

121

52

54

79

22

23

351

3.51 ± 0.81b

A, amorphous; B, banana shaped; H, hookless, F, folded; DH, double headed; DT, double tailed. (a)P < 0.05, (b)P < 0.01, (c)P < 0.001 (paired t-test). * 2000 sperm/animal. Al = aluminium acetate.

 

Applicant's summary and conclusion