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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

The reproductive toxicity to Ammonium molybdate (13106-79-8) was considered to be NOAEL at 260.58 µmol /L /day concentration in Hartley Albino guinea pigs and their offspring.

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer reviewed journal
Qualifier:
equivalent or similar to
Guideline:
other: As mention below
Principles of method if other than guideline:
Reproductive study of ammonium molybdate was performed on guinea pig.
GLP compliance:
not specified
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): ammonium molybdate(VI)
- Molecular formula: MoO4.2H4N
- Molecular weight: 196.0132 g/mol
- Smiles notation: [Mo](=O)(=O)([O-])[O-].[NH4+].[NH4+]
- InChl: 1S/Mo.2H3N.4O/h;2*1H3;;;;/q;;;;;2*-1/p+2
- Substance type: Inorganic
- Physical state: Solid
Species:
guinea pig
Strain:
Hartley
Remarks:
Albino
Details on species / strain selection:
No data available
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: Mature
- Weight at study initiation: Female :500g and male:600g
- Fasting period before study: No data available
- Housing: Galvanized metal mesh cage
- Diet (e.g. ad libitum): Milne feeds containing 212µmol /kg Cu(ad libitum)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
Route of administration:
oral: drinking water
Type of inhalation exposure (if applicable):
not specified
Vehicle:
water
Remarks:
Distilled
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Test material was added in distilled water

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 0 and 5.11 mg/kg
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
- M/F ratio per cage:1:1
- Length of cohabitation: For each female ,male was introduced into cage twice a day for 8.00 to 10.00 and 19.00 and 21.00
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy: If copulation plug was found under the cage and /or sperm were detected in vaginal smear referred to as day 0.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility :No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]:No data available
- After successful mating each pregnant female was caged (how): Individually
- Any other deviations from standard protocol:No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Approx 63 days
Frequency of treatment:
Daily
Details on study schedule:
not specified
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
5.115 mg/kg bw/day
No. of animals per sex per dose:
Total: 12
0 mg/kg bw: 6
5.115 mg/kg bw: 6
Control animals:
yes, concurrent vehicle
Details on study design:
not specified
Positive control:
not specified
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily for aborted fetuses
- Cage side observations checked in table [No.?] were included. No data available

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: as per autopsy schedule

BODY WEIGHT: Yes
- Time schedule for examinations: body weight of dams and pups were recorded each week.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OTHER: In per-mating period all the animals’ received tap water containing 1 g L- ascorbic acid /L /day. After mating in treated group received 16mg L- ascorbic acid /L/day while neonatal guinea pig received 4mg L- ascorbic acid/day in 0.125 ml distilled water up to 14 days old and there after 8mg L- ascorbic acid/day in 0.25ml distilled water until 6 weeks old .
Oestrous cyclicity (parental animals):
Yes
Sperm parameters (parental animals):
not specified
Litter observations:
Viability,clinical signs, Body weight and weight gain were examined.
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: yes
- Maternal animals: yes ( All the animals were anaesthetised with diethyl ether and blood was withdrawn by cardiac puncture into heparinised tubes and animals killed )

GROSS NECROPSY:
- No data available

HISTOPATHOLOGY / ORGAN WEIGHTS:
Pancreas of two dams in each group were examined
Postmortem examinations (offspring):
SACRIFICE
-At birth 2 animals of each litter were retained with dam for 6 weeks then both pups were killed. Young in excess of 2 were killed at birth.

GROSS NECROPSY: No data available


HISTOPATHOLOGY / ORGAN WEIGTHS: Sample of liver ,kidney ,sciatic nerve, gastrocnemius muscle, femur ,brain , spinal cord were carried out
Statistics:
Statistics was done using two sample t test using equal and unequal variances.
Reproductive indices:
No data available
Offspring viability indices:
Yes, on day 0, 4 and 6 weeks.
Clinical signs:
no effects observed
Description (incidence and severity):
No clinical sign of toxicity were observed in treated rats as compared to control.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality were observed in treated rats as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of treated female rats were observed as compared to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No significant change were observed on RBC, haemoglobin and mean corpuscular haemoglobin concentration in treated rats as compared to control.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Significant histological changes were in pancreas such as atrophy, lysis of single cells, loss of acinar pattern and vacuolation of acinar cells.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect on estrous cycle of treated rats were observed as compared to control.
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on Number pregnant, Aborted resorbing, Stillborn and Born alive in treated rats as compared to control.
Dose descriptor:
NOAEL
Effect level:
5.115 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
haematology
gross pathology
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
mortality observed, non-treatment-related
Description (incidence and severity):
No effect on viability of pups were observed as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on body weight of pups at week 6 were observed as compared to control.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
No significant change were observed on RBC, haemoglobin and mean corpuscular haemoglobin concentration in treated rats as compared to control.
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Significant histological changes were in pancreas such as atrophy, lysis of single cells, loss of acinar pattern and vacuolation of acinar cells in six weeks old pups.
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
5.115 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
body weight and weight gain
haematology
Remarks on result:
other: No effect observed
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Clinical signs and deaths in adult guinea pigs

Group

A

B

C

D

E

F

 

Before and after mating

After mating

Treatment

Control

AM

TM

TM

TM

TM

µmol litre -1

0

261

261

130

261

130

Number in group

8

8

8

8

8

8

Loss of hair

around mouth and ears

0

0

6

0

4

0

Transient diarrhea

0

0

1

0

4

0

Died pregnant

0

0

2

0

3

0

Died non pregnant

0

0

1

1

0

1

Killed during pregnancy

0

0

1

2

5

0

Ossified ridge in animals killed

0/8

0/8

3/5

0/7

4/5

1/7

Reproductive performance and viability of offspring of guinea pigs given AM or TM

Group

A

B

C

D

E

F

 

Before and after mating

After mating

Treatment

Control

AM

TM

TM

TM

TM

µmol litre -1

0

261

261

130

261

130

Adults

 

 

 

 

 

 

Number in group

8

8

8

8

8

8

Number pregnant

7

4

6

6

8

6

Fetuses

 

 

 

 

 

 

Number

23

12

16

21

21

19

Aborted resorbing

0

0

9

0

15

0

Stillborn

2

2

4

11

6

1

Born alive

21

10

 3

10

0

18

Pups killed at 6 weeks

 

 

 

 

 

 

Number of pups killed

14

7

3

8

 

 

 Weight at birth (g) (SE)

114-4 (4.3)

116.0

(2.3)

107.6

(3.1)

108.8

(3.3)

NA

106.1

(9.7)

Weight gain (g) from birth (SE)

3642 (31.3)

376.9

(12.7)

317.4

(28.1)

343.5

(36.4)

NA

407.6

(21.1)

 

Conclusions:
NOAEL was considered to be 5.115 mg/kg bw when Hartley Albino female guinea pig were treated with ammonium molybdate orally in drinking water approx. 63 days.
Executive summary:

In Reproductive toxicity test, Hartley Albino female guinea pig were treated with ammonium molybdate in the concentration of 0 and 5.115 mg/kg bw orally in drinking water. No mortality, clinical sign, change in body weight, no change in RBC, haemoglobin and mean corpuscular haemoglobin concentration and gross pathology were observed in treated rats as compared to control. Similarly, no effect on estrous cycle, Number pregnant, aborted resorbing, Stillborn and Born alive in treated rats as compared to control. Significant histological changes were in pancreas such as atrophy, lysis of single cells, and loss of acinar pattern and vacuolation of acinar cells. In addition, No effect on viability, body weight and hematology of pups were observed as compared to control. Significant histological changes were in pancreas such as atrophy, lysis of single cells, and loss of acinar pattern and vacuolation of acinar cells in six weeks old pups. The effects on pancreas were considered to result from copper deficiency rather than molybdenum toxicity. Therefore, NOAEL was considered to be 5.115 mg/kg bw when Hartley Albino female guinea pig were treated with ammonium molybdate orally in drinking water approx. 63 days.

 

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
260.58 µg/kg bw/day
Study duration:
subacute
Species:
guinea pig
Quality of whole database:
K2 and from peer reviewed journal
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Description of key information

Reproductive toxicity

In different studies,Ammonium molybdate (13106-79-8)has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments i.e. most commonly in rats and guinea pig forAmmonium molybdate (13106-79-8).

 

In experimental study given byJ.Mcc Howell,Y.Shunxiang, J.M.Gawthorne(Research in veterinary science, 1993, 55, 224-230)Ammonium molybdate (13106-79-8)was tested for reproductive toxicity.Reproductive toxicity test was performed in Hartley Albino guinea pigs in a group 8 at concentration of dose260.58µmol /L/day in distilled water by oral route .The mature female animals entered in third oestrous cycle for each female, male was introduced into cage twice a day for 8.00 to 10.00 and 19.00 and 21.00, If copulation plug was found under the cage and /or sperm were detected in vaginal smear then it is considered to have mated. Cage side observation done daily for aborted fetus , At birth 2 animals of each litter were retained with dam for 6 weeks then both pups were killed. Young in excess of 2 were killed at birth. Body weight of dams and pups were recorded each week.

All the animals were sacrifice and histopathological changes in pancreas observed in dam and in six week old pup like atrophy, lysis of single cells, loss of aciner pattern and vacuolation of acinar cells, thinning, beading and fragmentation or loss of reticulum fibres. Ammonium molybdate did not appeared to have adverse effect atconcentration of dose260.58µmol /L/day in distilled water by oral routeTherefore, the endpoint for reprotoxicity to Ammonium molybdate (13106-79-8) was considered to be NOAEL at 260.58 concentration in Hartley Albino guinea pigs.

 

It is further supported by experimental study given byGeeta Pandey and Gyan Chand Jain(Int.J.Curr.Microbiol.App.Sci (2015) 4(1): 150-161).Reprotoxicity test was performed in male wistar rats. 8 animals per group in dose concentration 50, 100, 150 mg/kg/day.Group with dose concentration 150 mg /kg /day were considered as recovery group. The Ammonium molybdate dissolved in water and given by oral route while control group received only vehicle .The rats were sacrificed within 24 h of the last administration of the compound and organ weight were calculated and blood samples were also collected. Histomorphometric observations and Histopathology of testis were studied. Effects of chemical on seminiferous tubule diameter, Leydig cell area and nuclear diameter were observed. In histopathology of testis degeneration in spermatogenic and Leydig cells, shrinked seminiferous tubules, thinner germinal epithelium, exfoliation of germ cells and depletion of spermatozoa from lumen of seminiferous tubule were observed. 60 days of recovery testicular histoarchitecture represented almost normal appearance. Therefore, the endpoint for reprotoxicity to Ammonium molybdate (13106-76-8) was considered to be LOAEL at 50 mg/kg/day in male wistar rat.

 

 Based on the above study on Ammonium molybdate (13106-79-8), it can be concluded that NOAEL value is 260.58

µmol /L/day

Justification for classification or non-classification

 Based on the above study on Ammonium molybdate (13106-79-8), it can be concluded that NOAEL value is 260.58

µmol /L/day