Aluminium potassium bis(sulphate)

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented study but not according OECD guideline

Data source

Reference

Reference Type:

publication

Title:

Studies on the toxicity of insecticides and food additives in pregnant rats. 2. Fetal toxicity of alum

Author:

Kanoh, S., Ema, M., Kawasaki, H.

Year:

1982

Bibliographic source:

Pharmacometrics, 24 (1), pp. 65-69

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Al2(SO4)3*K2SO4*24H2O

IUPAC Name:

Al2(SO4)3*K2SO4*24H2O

Details on test material:

Aluminium potassium bis(sulphate) as 24-hydrate

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

Environmental conditions:Temperature: 24+/- 1°CRelative humidity: 55+/- 5%

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Teratogenic effect of alum[Al2(SO4)3 . K2SO4 . 24H2O] was examined inWistar rats fed the diet containing 10, 2.5 or 0.32% of alum for seven days atthe second trimester of gestation. The effect on fetuses at day 20 of pregnancyand the effect on neonatal growth for four weeks after birth were examined.

Frequency of treatment:

Feeding: daily for 7 days at the second week of gestation

Duration of test:

Oral exposure: 7 days at the second week of gestationTotal test duration: 28 days

No. of animals per sex per dose:

16 female per dose

Control animals:

yes

Examinations

Maternal examinations:

Acute oral toxicity of female rats.Survival, food intake, body weight, relative organ weight of uterus and liver.

Ovaries and uterine content:

Uterus weight

Fetal examinations:

Food intake, substance intake, survival, live fetuses, weight, number of fetuses with external malfunctions, skeletal and visceral examinations

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:In acute oral toxicity of female rats no lethal effect was observed at dosesof 2.0, 1.0, 0.5 and 0.25 g/kg, but relative weight of liver was significantlyreduced in all experimental groups.Maternal body weight gain and food intake were reduced according to the dose of the substance.There were no differences among all the groups in the numbers of implantations andresorptions, but fetal weight in substance-administered groups was significantlyreduced compared with control.

Effect levels (maternal animals)

1

Dose descriptor:

other: LD0

Effect level:

>= 250 - <= 2 000 other: mg/kg bw

Based on:

test mat.

Remarks:

as AlK(SO4)2*12 H20

Basis for effect level:

other: other:

2

Dose descriptor:

other: LD0

Effect level:

>= 136 - <= 1 088 other: mg/kg bw

Based on:

test mat.

Remarks:

calculated as AlK(SO4)2 anhydrous

Basis for effect level:

other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:No external malformation of fetuses was observedin any group. Skeletal and visceral observations of fetuses indicated that therewas no significant difference in frequency of anomalies between control andexperimental groups.No adverse effect on postnatal growth was observed in 0.32%group, but the offspring in 10% group showed slow postnatal body weight gain.

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Effect level:

>= 0.32 - <= 10 other: % in diet

Based on:

test mat.

Remarks:

as AlK(SO4)2*12H2O in diet

Basis for effect level:

other: teratogenicity

2

Dose descriptor:

NOAEL

Effect level:

>= 121 - <= 4 031 mg/kg bw/day

Based on:

test mat.

Remarks:

calculated as AlK(SO4)2 anhydrous

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In the acute oral toxicity of female rats, no lethal effect was observed at dosesof 2.0, 1.0, 0.5 and 0.25 g/kg bw, but relative weight of liver was significantlyreduced in all experimental groups.In the teratogenic study, maternal bodyweight gain and food intake were reduced according to the dose of alum. Therewere no differences among all the groups in the numbers of implantations andresorptions, but fetal weight in alum-administered groups was significantlyreduced compared with control. No external malformation of fetuses was observedin any group. Skeletal and visceral observations of fetuses indicated that therewas no significant difference in frequency of anomalies between control andexperimental groups. No adverse effect on postnatal growth was observed in 0.32%group, but the offspring in 10% group showed slow postnatal body weight gain.From above results, it is concluded that alum possesses no teratogenic effect inrats fed the diet containing ranging from 0.32 to 10% during the secondtrimester of gestation.Calculated for Aluminium potassium bis sulphate anhydrous:LD0 = 250 - 2000 mg AlK(SO4)2*12 H2O/kg bw = 136 mg/kg bw - 1088 mg /kg bw Aluminium potassium bis sulphate.NOAEL: 0.32-10% Aluminium potassium bis sulphate*24H2O or AlK(SO4)2*12 H2O in diet - no teratogenic effects in rats.Calculated for Aluminium potassium bis sulphate anhydrous: NOAEL: 121 - 4031 mg/kg bw/day Aluminium potassium bis sulphate anhydrous - no teratogenic effects in rats.

Executive summary:

In the acute oral toxicity of female rats, no lethal effect was observed

at doses of 2.0, 1.0, 0.5 and 0.25 g/kg bw, but relative weight of liver was

significantly reduced in all experimental groups. In the teratogenic study,

maternal body weight gain and food intake were reduced according to the dose of alum.

There were no differences among all the groups in the numbers of implantations and

resorptions, but fetal weight in alum-administered groups was significantly reduced

compared with control. No external malformation of fetuses was observed in any group.

Skeletal and visceral observations of fetuses indicated that there was no significant

difference in frequency of anomalies between control and experimental groups.

No adverse effect on postnatal growth was observed in 0.32% group,

but the offspring in 10% group showed slow postnatal body weight gain.

From above results, it is concluded that alum possesses no teratogenic effect

in rats fed the diet containing ranging from 0.32 to 10% during the second trimester of gestation.

Calculated for Aluminium potassium bis sulphate anhydrous:

LD0 = 250 - 2000 mg AlK(SO4)2*12 H2O/kg bw = 136 mg/kg bw - 1088 mg /kg bw Aluminium potassium bis sulphate.

NOAEL: 0.32-10% Aluminium potassium bis sulphate*24H2O or AlK(SO4)2*12 H2O in diet - no teratogenic effects in rats.

Calculated for Aluminium potassium bis sulphate anhydrous:

NOAEL: 121 - 4031 mg/kg bw/day Aluminium potassium bis sulphate anhydrous - no teratogenic effects in rats.