Aluminium potassium bis(sulphate)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

There is no study information about other effects of Aluminium potassium bis (sulphate) available.

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented study according to OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Qualifier:

according to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Deviations:

no

GLP compliance:

yes

Species:

rat

Strain:

CD-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

Temperature: 21-25 °CRelative Humidity: 36-59%12h-dark/light cycleAir-conditioned room: ventilation at 10–15 times/h

Route of administration:

oral: drinking water

Vehicle:

water

Details on mating procedure:

Each female was mated with a single male of the same dosage group until successfulcopulation occurred or the mating period of 2 weeks had elapsed. For F1matings, cohabitation of siblings was avoided. During the mating period, vaginalsmears were examined daily for the presence of sperm, and the presence of spermin the vaginal smear and/or a vaginal plug were considered as evidence of successfulmating. The day of successful mating was designated as day 0 of gestation. Femalesthat did not mate successfully during the 2-week mating period were cohabited withanother male from the same group who had been proven to copulate with limits ofnot less than 7 days.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The substance was kept in a sealed container under cool and dark conditions. The test article was dissolved in ion-exchanged water, and served as drinking water to the animals. Control rats were given the ion-exchanged water alone as drinking water. Before the start of the study, the stability of the substance in ion-exchanged water at concentrations of 0.1, 0.6 and 15mg/mLwas confirmed after at least 4-day storage at room temperature following 6-dayrefrigerated storage; therefore, dosing solutions were prepared at least once every6 days and kept in a cool place until serving. Fresh drinking water was served at leastonce every 4 days. During the study, the concentrations of the substance in drinking water wereanalyzed in the first and last preparations and once every 3 months, and confirmedto be 97.5–106.3% of the target by high performance liquid chromatography. The substancecontained in the drinking water for the control group was less than the quantifiedlimit (5µg/mL).

Duration of treatment / exposure:

Dose finding study:Males were dosed for 7 weeks, beginning 14 days before mating, and females were dosed for 6–8 weeks beginning14 days before mating to day 4 of lactation throughout the mating and gestation period.Main study:Twenty-four F0 rats (5-week-old males and females)/sex/group were exposed toAluminium sulfate (AS) in drinking water at 0, 120, 600 or 3000 ppm. After 10-week administration of AS,each female rat was mated with a male rat of the same dosage group, and pregnantfemales were allowed to deliver spontaneously and nurse their pups. Administrationof AS was continued throughout the mating, gestation and lactation periods.F0 parental male rats were necropsied after the parturition of paired females. F0females were necropsied after weaning of their pups.For the second (F1) generation, 24 male and 24 female weanlings in each groupwere selected as F1 parents on PNDs 21–25 to equalize the mean body weightsamong groups as much as possible. One male and 1 female F1 weanlings wereselected from each of litters born during the 5 days including the day of the largestnumber of F0 parturition, and if the number of litters was insufficient, a secondweanling pup in the litter was selected with care to prevent litter effects. The day onwhich F1 parental animals were selected was designated as day 0 of dosing for the F1generation. F1-selected rats were given drinking water with the respective formulation,and were mated, allowed to deliver and nurse their F2 pups, and necropsiedin the same manner as described for F0 rats. Unselected F1 weanlings and all F2weanlings were necropsied on PND 26.

Frequency of treatment:

as fresh water every 4 days

Remarks:

Doses / Concentrations:120, 600, 3000 ppmBasis:analytical conc.

No. of animals per sex per dose:

Twenty-four F0 rats (5-week-old males and females)/sex/group

Control animals:

yes

Parental animals: Observations and examinations:

Throughout the study, all parental animals were observed for clinical signs oftoxicity at least twice a day. The body weight and food consumption were measuredweekly. For females exhibiting evidence of successful mating, body weight and foodconsumption were recorded on gestational days 0, 7, 14 and 20 of gestation anddays 0, 7, 14 and 21 of lactation (and additionally day 4 of lactation for body weight).Water consumption was recorded twice a week, and on days 0, 4, 7, 11, 14, 17 and20 of gestation and days 0, 4, 7, 11, 14, 17, 19 and 21 of lactation. The intake oftest substance was calculated based upon mean values for body weight and waterconsumption in each group.

Oestrous cyclicity (parental animals):

For each female, daily vaginal lavage samples were evaluated for estrous cyclicitythroughout the last 2 weeks of the premating period and during cohabitationuntil evidence of copulation was detected. Females having repeated 4–6 day estrouscycles were judged to have normal estrous cycles.

Sperm parameters (parental animals):

Sperm parameters were determined for all F0 and F1 male adults on theday of the scheduled sacrifice. The right testis was used to count testicularhomogenization-resistant spermatid heads. The right epididymal cauda wasweighed and used for sperm analysis. For sperm motility, the percentage of motilesperm and progressively motile sperm, and the swimming speed and pattern weredetermined using a computer-assisted cell motion analyzer (TOX IVOS; HamiltonThorne Bioscience, Beverly, MA, USA). After recording sperm motion, the cauda epididymalfluid was diluted and the sperm were enumerated with a hemacytometerunder a light microscope. Sperm count per gram of epididymal tissue was obtainedby dividing the total count by the gram weight of the cauda epididymis. The spermwas stained with eosin and mounted on a slide glass. Two hundred sperm in eachsample were examined under a light microscope, and the percentage of morphologicallyabnormal sperm was calculated.

Litter observations:

Once insemination was confirmed, female rats were checked at least three timesdaily on days 21–25 of gestation to determine the time of delivery. The females wereallowed to deliver spontaneously and nurse their pups until PND 21 (the day ofweaning). The day on which dams held their pups under the abdomen in the nest by13:00 was designated as day 0 of lactation or PND 0. On PND 0, all live and dead pupswere counted, and live pups were sexed and examined grossly. They were observeddaily for clinical signs of toxicity, and the body weight of live pups was recorded onPNDs 0, 4, 7, 14 and 21. On PND 4, litters were randomly adjusted to eight pups offour males and four females. No adjustment was made for litters of fewer than eightpups. Pups were assigned a unique number and limb tattooed on PND 4.

Postmortem examinations (parental animals):

All surviving parental male rats were euthanized by exsanguination under etheranesthesia after the parturition of paired females. All female rats showing successfulreproductive performance were evaluated for estrous cycle stage by examination ofthe vaginal smear after weaning of pups, and euthanized at the proestrous stageby exsanguination under ether anesthesia. Females that did not copulate or hadnot completed parturition and dams with total litter loss were euthanized in thesame way around the same time as females with successful reproduction. For allparental animals, the external surfaces were examined. The abdomen and thoraciccavity were opened, and gross internal examination was performed. Major organswere removed and the number of uterine implantation sites was recorded for eachfemale. The testis and epididymis were fixed with Bouin’s solution and preservedin 70% ethanol, and the other organs were stored in 10% neutral-buffered formalin.The brain, pituitary, thyroids, thymus, liver, kidneys, spleen, adrenals, testes,epididymides, seminal vesicles (with coagulating glands and their fluids), ventralprostate, uterus and ovaries were weighed before fixation. The thyroid and seminalvesicle were weighed after fixation.Histopathological evaluations were performed in all animals of the control andhighest dose groups, in females with abnormal estrous cycles, abnormal delivery ortotally dead pups, in males and females without evidence of copulation or insemination,and in all animals with grossly abnormal reproductive organs. Of theseanimals, the testes, epididymides, seminal vesicles, ventral prostate, coagulatinggland, ovaries, uterus and vagina, which were fixed as mentioned above, wereembedded in paraffin by a routine procedure. They were sectioned, stained withhematoxylin–eosin and examined histopathologically under a light microscope. Iftreatment-related histopathological changes were found in the highest dose group,were the same tissues from the next lower dose group then examined.In 10 F1 females, randomly selected from the control and highest dose groups,the number of primordial follicles was counted as follows. The right ovary, fixedin 10% neutral-buffered formalin, was dehydrated and then embedded in paraffinin longitudinal orientation by routine procedures. Sections were cut serially at5µm and every 20th section was serially mounted on a slide and stained withhematoxylin and eosin. About 40 sections per ovary were used to determine theprimordial follicles.

Postmortem examinations (offspring):

Following the adjustment of litter size on PND4, culled pups were euthanizedby inhalation of carbon dioxide and subjected to a gross external and internalobservation. Grossly abnormal organs/tissues were removed and stored in 10%neutral-buffered formalin. All pups found dead before weaning were necropsiedimmediately, and the whole body was stored in 10% neutral-buffered formalin.F1 weanlings not selected to become parents and all F2 weanlings were euthanizedand necropsied on PND 26, as described for adults. For one male and onefemale F1 and F2 weanlings selected from each dam, the brain, thymus, liver, kidneys,spleen, adrenals, testes, epididymides, ventral prostate, uterus and ovarieswere removed and the organ weights were measured. Major organs, including theweighed organs, were stored in 10% neutral-buffered formalin.Since test substance-related organ weight changes were found in the liver andspleen of the highest dose group, they were histopathologically examined for 10male and 10 female F1 and F2 weanlings in the control and highest dose groups. Theexamined animals were randomly selected from animals whose organs were stored.If treatment-related histopathological changes were observed in the highest dosegroup, were the same tissues from the next lower dose group then examined. Forthe histopathological examination, paraffin sections were routinely prepared andstained with hematoxylin and eosin.

Statistics:

Parametric data, such as body weight, food and water consumption, length of theestrous cycle and gestation, precoital interval, the number of implantations and pupsborn, delivery index, reflex response time, age at sexual maturation, parameters ofbehavioral tests, organ weight and sperm parameters, were analyzed by Bartlett’stest for homogeneity of distribution. For preweaning pups, body weight, AGD, viability,and age at the completion of developmental landmarks were similarly analyzedusing the litter as the experimental unit. When homogeneity was recognized, onewayanalysis of variance was performed. If a significant difference was detected,Dunnett’s test was conducted for comparisons between control and individual treatmentgroups. Data without homogeneity were analyzed using the Kruskal–Wallisrank sum test. If significant differences were found, the Mann Whitney’s U test wasconducted for comparison between the control and each dosage group. The incidenceof parental animals with clinical signs, and autopsy and histopathologicalfindings, the incidence of females with normal estrous cycles, incidence of weanlingswith histopathological findings, copulation, fertility and gestation index, neonatalsex ratio and completion rate of negative geotaxis were compared between the ASand control group using Fisher’s exact test. The incidence of pups with clinical signsor autopsy findings per litter, the completion rate of pinna unfolding in each litter,and the success rate of surface and mid-air righting reflex were analyzed bythe Wilcoxon rank sum test. The number of primordial follicles in the control andhighest dose groups was compared by Student’s t-test because the homogeneity ofvariance was indicated by the F-test. All of these statistical analyses were conductedusing the 5% level of probability as the criterion for significance.

Reproductive indices:

Reproductive performance of F0 and F1 parental animals:F0 generation:Copulation index (%)Fertility index (%)Delivery index (%)F1 generation:Copulation index (%)Fertility index (%)Delivery index (%)

Offspring viability indices:

Sex ratio, viability and body weight for F1 and F2 pups:F1 offspring:Sex ratio of pupsViability index of pups (%)Male pup weight during lactation (g)Female pup weight during lactation (g)F2 offspring:Sex ratio of pupsViability index of pups (%)Male pup weight during lactation (g)Female pup weight during lactation (g)

Clinical signs:

no effects observed

Description (incidence and severity):

No significant difference was seen between control and substance-treated groups in the incidence of clinical signs of toxicity in either male or female F0 rats.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Water consumption and food consumption decreased partially during test period. The body weight of F0 males and females was significantly lowered in the first 2 or 3 weeks of dosing at 3000 ppm.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Water consumption and food consumption decreased partially during test period. The body weight of F0 males and females was significantly lowered in the first 2 or 3 weeks of dosing at 3000 ppm.

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No significant change

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Test substance intake: With increasing aluminium sulphate concentration water consumption decreases. This effect was taken into account for the results.

Reproductive function: oestrous cycle:

no effects observed

Description (incidence and severity):

Adverse effects were not found in estrous cyclicity.

Reproductive function: sperm measures:

no effects observed

Description (incidence and severity):

Adverse effects were not found in sperm parameters.

Reproductive performance:

no effects observed

Description (incidence and severity):

See table 1 attached

Dose descriptor:

NOAEL

Effect level:

600 ppm (analytical)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observed for any parameters determined in the study

Dose descriptor:

NOAEL

Effect level:

41 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects observed for any parameters determined in the study

Clinical signs:

no effects observed

Description (incidence and severity):

No significant effects

Mortality / viability:

no mortality observed

Description (incidence and severity):

No significant effects

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Decreased body weight at PND 21 for 3000 ppm.

Sexual maturation:

no effects observed

Description (incidence and severity):

No significant effects

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Differences in absolute and relative organ weight for various organs: see table 3

Gross pathological findings:

no effects observed

Description (incidence and severity):

No significant effects

Histopathological findings:

no effects observed

Description (incidence and severity):

No significant effects

Remarks on result:

other: definitive conclusions could not be reached since paired-comparison data are not available to assess the effects of decreased water intake in the absence of exposure of Aluminium sulfate.

Reproductive effects observed:

not specified

In summary, Aluminium sulfate administered via drinking water at 120, 600 or 3000ppm

resulted in decreased water consumption. This change was associated with

decreased food consumption in the 600 and 3000ppm groups and decreased body

weight in the 3000ppm group. In the 3000ppm group, male and female pups had a

lower body weight on PND 21.

No definitive effects were found in the other reproductive/developmental parameters,

including developmental neurobehavioral toxicity.

Although there is a possibility that observed developmental effects are results

of decreased water consumption, more definitive conclusions could not be

reached since paired-comparison data are not available to assess the effects

of decreased water intake in the absence of exposure of Aluminium sulfate.

Conclusions:

Aluminium sulfate administered via drinking water at 120, 600 or3000ppm resulted in decreased water consumption. This changewas associated with decreased food consumption in the 600 and3000ppm groups and decreased body weight in the 3000ppmgroup. In the 3000ppm group, male and female pups had alower body weight on PND(Post Natal Day) 21. At this dose, vaginal opening wasslightly delayed. No definitive effects were found in the otherreproductive/developmental parameters, including developmentalneurobehavioral toxicity. Although there is a possibility thatobserved developmental effects are results of decreased water consumption,more definitive conclusions could not be reached sincepaired-comparison data are not available to assess the effects ofdecreased water intake in the absence of exposure of Aluminium sulfate.NOAEL : 600 ppm = 41.0 mg/kg bw/day Aluminium sulfateCalculated for Aluminium potassium bis sulphate:NOAEL > 31 mg Aluminium potassium bis sulphate/kg bw/daybecause the NOAEL of second read across substance potassium sulfate is 1500 mg/kg bw/day.

Executive summary:

Aluminium sulfate administered via drinking water at

120, 600 or 3000ppm resulted in decreased water consumption.

This change was associated with decreased food consumption in the

600 and 3000ppm groups and decreased body weight in the 3000ppm group.

In the 3000ppm group, male and female pups had a lower body weight on PND(Post Natal Day) 21.

At this dose, vaginal opening was slightly delayed.

No definitive effects were found in the other reproductive/developmental parameters,

including developmental neurobehavioral toxicity.

Although there is a possibility that observed developmental effects are results

of decreased water consumption, more definitive conclusions could not be

reached since paired-comparison data are not available to assess the effects

of decreased water intake in the absence of exposure of Aluminium sulfate.

NOAEL : 600 ppm = 41.0 mg/kg bw/day Aluminium sulfate

Calculated for Aluminium potassium bis sulphate:

NOAEL > 31 mg Aluminium potassium bis sulphate/kg bw/day because the NOAEL

of second read across substance potassium sulfate is 1500 mg/kg bw/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

31 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

NOAEL aluminium potassium bis sulphate was calculated from NOAEL aluminium sulfate and should be > 31 mg/kg bw/day because the NOAEL of potassium sulfate for toxicity of reproduction is 1500 mg/kg bw/day.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction

No effects on fertility were observed for concentration up to 3000 ppm (max).

Based on the Key study on aluminium sulfate as Read-across substance and OECD Supporting study on potassium sulfate as Read-across substance the calculated NOAEL for aluminium potassium bis sulphate from NOAEL aluminium sulfate (41 mg/kg bw/day) is 31 mg aluminium potassium bis sulphate. The NOAEL of aluminium potassium bis sulphate should be higher than the calculated NOAEL of 31 mg/kg bw/day because the NOAEL of potassium sulfate for toxicity of reproduction is 1500 mg/kg bw/day. The LOAEL could not be determined because there were not any adverse effects ascertained. Aluminium potassium bis sulphate dissociates in water to ions the AL 3+, K+ and SO42- which are the same as the ions of the dissolved Read-across substances Aluminium sulfate and potassium sulfate.

Short description of key information:
Based on the Key study on aluminium sulfate as Read-across substance and OECD Supporting study on potassium sulfate as Read-across substance the calculated NOAEL for aluminium potassium bis sulphate from NOAEL aluminium sulfate (41 mg/kg bw/day) is 31 mg aluminium potassium bis sulphate. The NOAEL of aluminium potassium bis sulphate should be higher than the calculated NOAEL of 31 mg/kg bw/day because the NOAEL of potassium sulfate for toxicity of reproduction is 1500 mg/kg bw/day. The LOAEL could not be determined because there were not any adverse effects ascertained. Aluminium potassium bis sulphate dissociates in water to ions the AL 3+, K+ and SO42- which are the same as the ions of the dissolved Read-across substances Aluminium sulfate and potassium sulfate.

Justification for selection of Effect on fertility via oral route:
Well documented study according OECD guideline 416 (Two-Generation Reproduction Toxicity Study)
of Aluminium sulfate as read across substance of Aluminium potassium bis sulphate.
No effects on fertility were observed for concentration up to 3000 ppm (max).
In summary, Aluminium sulfate administered via drinking water at 120, 600 or
3000ppm resulted in decreased water consumption. This change
was associated with decreased food consumption in the 600 and
3000ppm groups and decreased body weight in the 3000ppm
group. In the 3000ppm group, male and female pups had a
lower body weight on PND 21.
No definitive effects were found in the other reproductive/developmental parameters,
including developmental neurobehavioral toxicity.
Although there is a possibility that observed developmental effects are results
of decreased water consumption, more definitive conclusions could not be
reached since paired-comparison data are not available to assess the effects
of decreased water intake in the absence of exposure of Aluminium sulfate.
Based on the NOAEL of Aluminium sulfate the NOAEL of Aluminium potassium
bis sulphate was calculated for the observed developmental effects,
but the NOAEL of aluminium potassium bis sulphate should be higher
than the calculated NOAEL of 31 mg/kg bw/day because the NOAEL
of potassium sulfate for toxicity of reproduction is 1500 mg/kg bw/day.

Effects on developmental toxicity

Description of key information

NOAEL-28d oral rat: 121 - 4031 mg/kg bw/day as Aluminium potassium bis sulphate anhydrous under the test conditions.

Link to relevant study records

Reference

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

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Deviations:

not specified

GLP compliance:

not specified

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

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

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

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

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.

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:

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:

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.

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

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

Abnormalities:

not specified

Developmental effects observed:

not specified

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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

4 031 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

NOAEL of the substance: 121 - 4031 mg/kg bw/day as Aluminium potassium bis sulphate anhydrous without any teratogenic effect to test animals based on calculation from NOAEL of Aluminium potassium bis sulphateas 0.32 - 10 % in diet.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Development toxicity/teratogenicity

Based on the well documented key study on development toxicity/ teratogenicity from Kanoh et al. (1988) and the OECD SIDS report as supporting study with potassium sulfate as read across substance of aluminium potassium bis sulphate, it is concluded that aluminium potassium bis sulphate 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.

Based on the OECD SIDS report as supporting study of potassium sulfate as read across substance there are the following results:

Toxicity subgroup: There were no treatment-related deaths and no signs of overt clinical toxicity. There were no effects on body weight, food consumption, or food efficiency. Functional observational battery (FOB) and motor activity tests identified no treatment-related changes in behavior, function, or motor activity. No treatment-related histopathological changes were reported.

NOAEL: 1500 mg/kg bw/day (general toxicity)

LOAEL: No adverse effects were seen on general toxicity endpoints.

NOAEL-28d oral rat: 121 - 4031 mg/kg bw/day as Aluminium potassium bis sulphate anhydrous

under the test conditions.

Justification for selection of Effect on developmental toxicity: via oral route:
Well documented study not according OECD guideline

Justification for classification or non-classification

Based on the results of Key study and Supporting study on toxicity to reproduction of the Read across substances aluminium sulfate and

potassium sulfate and Key study and Supporting study on development toxicity of aluminium potassium bis sulphate 24 -hydrate and

the Supporting OECD study of potassium sulfate the substance aluminium potassium bis sulphate is not classified for toxicity to reproduction according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).