Aluminium nitrate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test guideline (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Report meets generally accepted scientific standards, well documented and acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Principles of method if other than guideline:

Male rats were treated orally for 60 days prior to mating and female rats were treated for 14 days prior to and throughout the mating period, gestation, delivery, and lactation.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna Iberica, Spain
- Weight at study initiation: (P) Males: 240-280 g; Females: 240-280 g
- Diet: ad libitum, high protein rat diet (Panlab, Barcelona, Spain)
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 2 °C
- Humidity (%): 55 +- 5 %

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
no data

Dose levels were selected to approximate to 1/20, 1/10, and 1/5 of the acute oral LD50 value estimated for aluminium nitrate.

Male rats were treated by gavage for 60 days prior to mating and the females were dosed for 14 days prior to mating and then throughout the mating period, gestation, delivery and lactation.

Details on mating procedure:

Groups of 25 females were used at each dose level. Following pairing with treated males, proof of pregnancywas indicated by sperm in vaginal smears. The day sperm were observed was referred to as day 0 of pregnancy (Gestation day 0)

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

Male rats were dosed for 60 days prior to mating and female rats were treated for 14 days prior to and throughout the mating period, gestation,
delivery, and lactation.

Frequency of treatment:

Daily

Details on study schedule:

Males were treated for 60 days and females for 14 days prior to pairing. The rats were mated within the dose group. Day 0 of gestation was taken as the day sperm were observed in the vaginal smear. Dams were treated throughout the gestation and lactation phases. On Day 13 of gestation half of the dams in each group were terminated and examined to determine the number of corpora lutea, total number of implantations, early and late resorptions and the number of live and dead foetuses. The remaining dams were allowed to litter and nurse the neonates to day 21 of lactation

Remarks:

Doses / Concentrations:
0, 180, 360, 720 mg/kg bw/d
Basis:
actual ingested
aluminium nitrate nonahydrate

Remarks:

Doses / Concentrations:
0, 102, 204, 409 mg/kg bw/d
Basis:
actual ingested
equivalent dose anhydrous aluminium nitrate

No. of animals per sex per dose:

25

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: doses were selected based on a prior 100 days study at 1/20, 1/10 and 1/5 of the LD50 (gavage)

Positive control:

no data

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Not specified

FOOD CONSUMPTION: Not specified

WATER CONSUMPTION: Not specified

Oestrous cyclicity (parental animals):

Not specified

Sperm parameters (parental animals):

Parameters examined in male parental generations: not specified

Litter observations:

STANDARDISATION OF LITTERS
Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in [F1] offspring: mortality, normal body weight gain, body and tail lengths and general symptomatology after 1, 4, and 21 days of nursing

Postmortem examinations (parental animals):

On day 13 of gestation, one-half of the dams from each group were killed. The following examinations were made: determination of the number of corpora lutea, total implantations, living and dead fetuses as well as the number of early and late resorptions.

Postmortem examinations (offspring):

The offspring were killed after 21 days; heart, lungs, spleen, liver, kidneys, brain, and testicles were removed and weighed. The ratios of organ weight/body weight, were calculated.

Statistics:

Statistical analyses were made by means of the distribution-free ranking test according to Wilcoxon in the modified version of Mann-Whitney, and using the chi-square test. The effect of aluminium on relative organ weights of rats pups was evaluated by the Kruskal-Wallis statistical test. In all cases a minimum level of significance of P < 0.05 was used.

Reproductive indices:

not specified

Offspring viability indices:

not specified

Clinical signs:

no effects observed

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Fertility rates and reproductive data were unaffected by the treatment. Treatment with aluminium did not affect the survival of adult rats and no deaths were noted in any group. The percentage of pregnant females was similar in each treatment group.

Dose descriptor:

NOAEL

Remarks:

general toxicity

Effect level:

720 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects were reported

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

720 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects were reported

Clinical signs:

not examined

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:

not examined

Histopathological findings:

not examined

Data from rat pups nursed by aluminium-treated mothers are presented on days 1, 4 and 21 after birth. The number of litters was lower for the aluminium-treated groups (mid and high dose). Although survival of rats was rather low for all groups, the number of living young per litter was lower for the aluminium-treated groups. On the other hand, the number of dead young per litter was higher for these groups. The differences were more remarkable for the high dose group. Body weight, body length and tail length of the rat pups in the treated groups showed significant decreases when compared with the control group.
The fresh organ weights of rat pups killed after 21 days of lactation were measured in ten animals from each group. There were no significant differences between the control and treated groups when expressed relative to body weight.

The number of litters was decreasing with time, and the dead/living ratio and the number of dead young per litter were increasing during the lactation. Dose-response relationships could be induced.
With regard to the growth of the offspring as a measure of body weight, body length and tail length, it was always significantly lower for the treated groups. These decreases must be imputed to the treatment and an important dose response relationship can be remarked. However, the significance of the differences was decreasing with time.
On the other hand, no hypertrophy or hypotrophy in the organs removed after the treatment could be detected.

Dose descriptor:

LOAEL

Remarks:

developmental toxicity

Generation:

F1

Effect level:

180 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Reduced litter numbers, litter size and offspring viability

Reproductive effects observed:

not specified

 

The effect of oral administration of aluminium in Sprague-Dawley rats on gestation day 13

	Dose level mg/kg bw/d  aluminium nitrate nonahydrate (Al(NO3)3.9H2O)
	0	180	360	720
Litters	9	7	10	10
Corpora lutea	18.2	16.9	15.9	14.5^a
Total implants	13.7	13.1	12.5	14.0
Early resorptions	0.1	0.7	0.1	0.8
Late resorptions	1.5	0.9	1.4	1.1
Live foetus	12.1	11.1	10.8	10.8
Dead foetus	0.1	0.4	0.2	0.3
^asignificantly different from controls P<0.05

 

 

 

Summary of data for pups nursed by aluminium treated mothers

	Day	Dose level mg/kg bw/d  aluminium nitrate nonahydrate (Al(NO3)3.9H2O)
		0	180	360	720
No. of litters	1 4 21	9 9 9	10 10 10	7 7 7	7 5 4
No. of living young	1 4 21	108 106 66	115 108 56	91 83 27	66 52 19
No. of dead young	1 4 21	0 2 40	2 7 52	2 8 56	12 14 33
Dead/living ratio (x100)	1 4 21	0.0 1.9 37.7	1.7 6.1 48.1	2.2 8.8 67.5	18.1 21.2 63.5
Male/female ratio	1 4 21	1.00 0.96 0.94	0.90 1.03 1.00	0.65 0.69 0.50	0.94 0.86 1.11
Living young/litter	1 4 21	12.0 11.9 7.3	11.5 10.8 5.6	13.0 11.9 4.5^a	9.4 10.4 4.8^a
Dead young/litter	1 4 21	0.0 0.2 4.4	0.2 0.7 5.2	0.3 1.1 9.3	1.7 2.8 8.3
^asignificantly different from controls P<0.05

 

 

Effects of aluminium nitrate on rat pups nursed by aluminium treated mothers

	Sex	Day	Dose level mg/kg bw/d  aluminium nitrate nonahydrate (Al(NO3)3.9H2O)
			0	180	360	720
Bodyweight (g)	M	1 4 21	7.2 (54) 9.3 (52) 39.9 (32)	6.9 (55) 9.4 (55) 40.7 (28)	6.7 (36)^a 9.4 (34) 32.4 (9)^a	6.2 (32)^c 8.6 (24)^a 29.7 (10)^b
	F	1 4 21	6.9 (54) 9.3 (54) 36.3 (34)	6.3 (60)^a 8.7 (53) 38.1 (28)	6.3 (55)^a 9.2 (49) 38.6 (18)	6.1 (34)^c 8.3 (28)^b 30.9 (9)^a
Body length (mm)	M	1 4 21	55.4 64.0 118.4	54.8 63.0 115.7	53.3^b 62.4 110.3^a	51.8^c 61.2^b 110.3^a
	F	1 4 21	55.3 63.9 116.6	52.6^b 63.8 118.2	52.6^b 60.6^b 116.6	52.0^c 59.8^c 114.0
Tail length (mm)	M	1 4 21	20.4 25.8 77.2	19.8 24.5 76.5	18.7 24.0^b 76.0	17.2^b 23.0^c 62.0^b
	F	1 4 21	20.2 27.3 74.6	18.7^a 24.6^a 75.3	17.9^b 24.0^a 73.8	17.7^c 23.4^b 71.1^b
^a,b,csignificantly different from controls P<0.05; <0.01 or <0.001 M/F male/female (number of animals studied)

 

Conclusions:

Fertility rates and reproductive indices were unaffected in the parents but numbers of litters reduced in aluminium treated rats and the ratio of dead to living pups and the number of dead pups showed an increase duration lactation. Pup growth as measured by bodyweight, body length and tail length indices was inhibited in treated groups. The lowest dose level, 180 mg/kg bw/d, resulted in some adverse effects in the offspring in this study although no effects were apparent in the parents.

Executive summary:

 Aluminium nitrate was tested for its effects on reproduction, gestation, and lactation in Sprague-Dawley rats, at dosages of 0, 180, 360 and 720 mg/kg bw/d. Mature male rats were treated orally for 60 days prior to mating with mature virgin female rats treated for 14 days prior to mating with treatment continuing throughout mating, gestation, parturition, and weaning of the litters. One-half of the dams in each group were killed on Day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored. No adverse effects on fertility or general reproductive parameters were evident at doses employed in these studies, however effects on post-natal pup growth and survival were apparent in all treated groups.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

102 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

A number of studies are available for this endpoint, including a screening study and one-generation study.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No effects on fertility were observed in an OECD 422 screening study (Beekhuijzen, 2007) performed with aluminium chloride at dose levels of up to 1000 mg/kg bw/d (equivalent to 90 mg/kg bw/d Al3⁺).  In a one-year developmental / neurotoxicity performed with aluminium citrate (ToxTest, 2010), no effects on fertility were observed at dose levels of up to 3225 mg/kg bw/d (300 mg/kg bw/d (Al3⁺); however reduced post-natal survival was seen at this dose level.  A one generation study performed with aluminium nitrate (Domingo et al, 1987) similarly demonstrates an absence of effects on fertility but indicates effects on pup growth and survival at all dose levels (≥180 mg/kg bw/d) although a dose-response relationship is not always apparent. Llobet et al (1995) demonstrate that the administration of aluminium nitrate by intraperitoneal injection at dose levels of 50, 100 or 200 mg/kg bw/d resulted in systemic toxicity; effects on the male reproductive tract and fertility were seen at 100 and 2000 mg/kg bw/d. The results of this study are not considered to be of direct relevance to the human risk assessment due to the non-physiological route of administration and the known low bioavailability of aluminium nitrate.

The findings of reduced offspring growth and survival from the reproductive study with aluminium nitrate are not consistent with those of the longer term study with aluminium citrate, in which effects were observed only at a much higher dose level. Additionally the oral bioavailability of aluminium is known to be significantly enhanced by the presence of citrate.

Short description of key information:
A screening study (OECD 422) is available for the read-across substance aluminium chloride; a one-generation study study is available for aluminium nitrate and a chronic study is available for aluminium citrate. A study of male fertility using aluminium nitrate is considered to be of limited relevance due to the use of intraperitoneal dosing.

Justification for selection of Effect on fertility via oral route:
One-generation study showing adverse effects

Effects on developmental toxicity

Description of key information

A guideline-comparable developmental toxicity study in the rat is available for aluminum nitrate

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: Report meets generally accepted scientific standards, well documented and acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Three groups of ten pregnant rats were exposed to the test substance from day 6-14 of gestation at three different dose levels.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna Iberica, Spain
- Weight at study initiation: 240-280 g
- Housing: 1 male was cohoused with 2 females until copulation was detected
- Diet: ad libitum, Panlab diet, Barcelona, Spain
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23 °C
- Humidity (%): 50 +- 5 %
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The aluminum nitrate solutions were prepared to give a dose in a volume of 1 ml/250 g body weight.
Dose levels of aluminium nitrate nonahydrate were 180, 360 and 720 mg/kg bw/day

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1 male / 2 females
- Length of cohabitation: until copulation was detected
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: sperm in vaginal smear referred to as day 1 of pregnancy

Duration of treatment / exposure:

from day 6 to day 14 of gestation

Frequency of treatment:

daily

Duration of test:

continuous dosing until day 20 of gestation

Remarks:

Doses / Concentrations:
0, 180, 360, 720 mg/kg bw/d
Basis:
actual ingested
test material

Remarks:

Doses / Concentrations:
0, 102, 204, 409 mg/kg bw/d
Basis:
actual ingested
anhydrous aluminium nitrate

No. of animals per sex per dose:

four groups of ten pregnant rats (incl. control group)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: doses were selected based on a prior 100 days study at 1/20, 1/10 and 1/5 of the LD50 (gavage)

Maternal examinations:

CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Not specified, weight gain during gestation was determined

POST-MORTEM EXAMINATIONS: Not specified

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included: number of corpora lutea, total implantations, number of live and dead fetuses, number of resorptions, average fetal body weights, number of stunted fetuses (under 2/3 average body weigth), placental weights per litter, fetal body lengths and fetal tails lengths per litter.

Fetal examinations:

- External examinations: Yes: [all per litter]
- Skeletal examinations: Yes: [more than half per litter]
- Soft tissue examinations: Yes: [the remainder of the litter]
- Head examinations: No data

Statistics:

All statistical analyses compared the treatment groups to the control group with the level of significance at P<0.05. Maternal body weights, fetal body weights, fetal body lengths, fetal tail lengths, corpora lutea, implantations, resorptions, and live and dead fetuses were analyzed statistically using a one-way analysis of variance and Mann-Whitney U test. Fetal abnormalities were analyzed using the chi-square test criterion with Yates' correction for 2 x 2 contingency tables and/or Fisher's exact probability test to judge significance of differences.

Indices:

no data

Historical control data:

no data

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Dams given aluminium nitrate gained significantly (P< 0.01) less body weight than the control dams throughout the gestation period.

Dose descriptor:

LOAEL

Effect level:

180 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Dose descriptor:

LOAEL

Effect level:

180 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Aluminium-nitrate intubation had no significant adverse effects on the following parameters: number of corpora lutea, number of implantations, number of resorptions, and number of live and dead fetuses. These values were similar for the treated and the control groups. Nevertheless, the number of runt fetuses as well as the number of litters with runt fetuses showed recognizable dose-dependent increases in the aluminium-treated groups.
Body weight and tail length of fetuses from the treated groups showed significant decreases (P< 0.001) compared with the control values. Also, body length was significantly lower in the fetuses from the high dose group. The average weight of placentas decreased significantly in the mid and high dose groups.
The most common statistically significant increased variations and visceral malformations were hematomas (especially in abdominal cavity and thorax), renal hypoplasia, and dextrocardia in the high dose group. Furthermore, fetal examinations revealed effects on skull (decreased ossifications of supraoccipital bone), ribs (hypoplastic deformations; vertebral alterations), and sternebrae (partial ossification; bilobed appearance; other variations) in all treatment groups.

Abnormalities:

not specified

Developmental effects observed:

not specified

Effects of aluminium nitrate administered by gavage to rats during gestation day 6-14

	Dose level mg/kg bw/d   aluminium nitrate nonahydrate (Al(NO3)3.9H2O)
	0	180	360	720
Number of litters	10	8	7	8
No. of corpora lutea	14.5	13.9	15.6	15.4
No. of total implants	12.5	10.3	13.2	13.4
No. of live foetuses	12.3	9.3	12.5	12.8
No. of resorptions	0.2	0.3	0.5	0.5
No. of dead foetuses	0.0	0.7	0.2	0.1
No. of total foetuses	126	83	88	101
No. of runt foetuses	0	4	6	20
No. of litters with runt foetuses	0	2	3	5
Weight gain during gestation (g)	122	99.4	97.9	98.8
Placental weight (g)	1.05	1.06	0.82	0.89
Mean foetal bodyweight (g)	3.29	2.82	2.75	2.19
Mean foetal body length (mm)	37.9	38.5	37.3	34.7
Mean foetal tail length (mm)	13.0	11.5	11.7	11.1
^*significantly different from controls P<0.05

summary of malformations and variations in rats given aluminium nitrate during organogenesis

Malformations	Dose level mg/kg bw/day   aluminium nitrate nonahydrate (Al(NO3)3.9H2O)
	0	180	360	720
External
No. of foetuses observed	126	83	88	101
Oedema	0 (0.0)	0 (0.0)	2 (2.27)	3 (2.97)
Micrognathia	0 (0.0)	0 (0.0)	7 (7.95)**	2 (1.98)
Oligodactyly	0 (0.0)	0 (0.0)	0 (0.0)	2 (1.98)
Visceral
No. of foetuses observed	42	27	29	33
Microphthalmia	0 (0.0)	0 (0.0)	2 (6.89)	0 (0.0)
Anophthalmia	0 (0.0)	0 (0.0)	4 (3.79)	3 (9.09)
Telencephalaic hypoplasia	0 (0.0)	0 (0.0)	1 (3.44)	0 (0.0)
Renal hypoplasia	0 (0.0)	0 (0.0)	0 (0.0)	4 (12.12)
Hydrocephaly	0 (0.0)	0 (0.0)	1 (3.44)	2 (6.06)
Dextrocardia	0 (0.0)	0 (0.0)	0 (0.0)	4 (12.12)
Skeletal
No. of foetuses observed	84	56	59	68
Skull
Decreased ossification of supraoccipital bone	0 (0.0)	5 (8.92)*	6 (10.16)*	38 (68.0)***
Ribs
Hyoplastic deformed	2 (2.38)	27 (48.21)***	14 (23.72)**	14 (20.58)**
Total vertebral alterations	5 (5.95)	25 (44.64)***	14 (23.72)*	15 (22.05)*
Sternebral variations
Partial ossification	10 (11.90)	12 (21.42)	27 (45.76)**	47 (69.11)***
Bilobed appearance	8 (9.52)	10 (17.86)	27 (45.76)**	47 (69.11)***
other	2 (2.38)	11 (19.64)**	11 (18.64)**	49 (72.05)***
Variations
No. of foetuses observed	126	83	88	101
Haematomas
In facial area	1 (0.79)	2 (2.40)	2 (2.27)	1 (0.99)
In abdominal cavity	2 (1.58)	2 (2.40)	4 (4.54)	13 (12.87)
In thorax	1 (0.79)	1 (1.20)	4 (4.54)	11 (10.89)
In limbs	1 (0.79)	1 (1.20)	2 (2.27)	7 (6.93)
^*significantly different from controls P<0.05 ^**significantly different from controls P<0.01 ^***significantly different from controls P<0.001

Conclusions:

Teratogenic effects were evident at maternally toxic dose levels in rats administered aluminium nitrate during the period of organogenesis. While the numbers of copora lutea, total implants, resorptions and live/dead ratios were not significantly affected in the treated groups, there were significant increases in the number of runts per litter in the treated groups, and treatment related malformations and variations were identified in all dose groups.

Executive summary:

The embryotoxic and teratogenic potential of aluminium was investigated in pregnant Sprague-Dawley rats. Daily doses of 0, 180, 360 or 720 mg/kg bw/d, were administered by oral gavage from the sixth to fourteenth day of gestation. Foetal examinations were completed on Gestation Day 20, including determination of numbers of corpora lutea, total implants, resorptions, live and dead foetuses. None of these parameters showed any significant changes in treated groups compared with controls. It was concluded from these data that embryolethality could not be induced, but exposure of rats to aluminium nitrate did result in decreased foetal bodyweight and an increase in the incidence, and type, of external, visceral and skeletal malformations and variations in all treated groups. High doses of orally administered aluminium nitrate results in teratogenic effects in rats at levels that induce concommitant maternal toxicity.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

102 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

A guideline-comparable developmental toxicity study is available

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

The embryotoxic and teratogenic potential of aluminium was investigated in pregnant Sprague-Dawley rats. Daily doses of 0, 180, 360 or 720 mg/kg bw/d, were administered by oral gavage from the sixth to fourteenth day of gestation. Foetal examinations were completed on Gestation Day 20, including determination of numbers of corpora lutea, total implants, resorptions, live and dead foetuses. None of these parameters showed any significant changes in treated groups compared with controls. It was concluded from these data that embryolethality could not be induced, but exposure of rats to aluminium nitrate did result in decreased foetal bodyweight and an increase in the incidence, and type, of external, visceral and skeletal malformations and variations in all treated groups. High doses of orally administered aluminium nitrate results in teratogenic effects in rats at levels that induce concommitant maternal toxicity.

The findings from the developmental toxicity study with aluminium nitrate are not consistent with those of the longer term study with aluminium citrate, in which effects were observed only at a much higher dose level. Additionally the oral bioavailability of aluminium is known to be significantly enhanced by the presence of citrate.

Justification for selection of Effect on developmental toxicity: via oral route:
Standard study design, reporting adverse effects

Justification for classification or non-classification

No classification proposed for aluminium nitrate based on the results of reproductive and developmental toxicity studies