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Diss Factsheets

Toxicological information

Toxicity to reproduction

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Administrative data

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Ammonium sulfate CAS N°: 7783-20-2
Author:
Anonymous
Year:
2004
Bibliographic source:
UNEP Publications: SIDS Initial Assessment Report SIAM 19, Berlin, Germany
Report date:
2004
Reference Type:
other: unpublished data
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
In the OECD SIDS report, unpublished data from an OECD 422 study conducted by the The Fertilizer Institute, 2002 on diammonium phosphate is cited.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Diammonium hydrogenorthophosphate
EC Number:
231-987-8
EC Name:
Diammonium hydrogenorthophosphate
Cas Number:
7783-28-0
Molecular formula:
H3N.1/2H3O4P
IUPAC Name:
diammonium hydrogen phosphate
Specific details on test material used for the study:
- Name of the test material: Diammonium phosphate

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
See "any other information on material and methods incl. tables".
Details on mating procedure:
See "any other information on material and methods incl. tables".
Duration of treatment / exposure:
See "any other information on material and methods incl. tables".
Frequency of treatment:
See "any other information on material and methods incl. tables".
Details on study schedule:
see box "Any other information on material and methods incl. tables"
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Control
Dose / conc.:
250 mg/kg bw/day (nominal)
Remarks:
Low-dose group
Dose / conc.:
750 mg/kg bw/day (nominal)
Remarks:
Mid-dose group
Dose / conc.:
1 500 mg/kg bw/day (nominal)
Remarks:
High-dose group
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
n.a.
Positive control:
n.a.

Examinations

Parental animals: Observations and examinations:
See "any other information on material and methods incl. tables".
Litter observations:
See "any other information on material and methods incl. tables".
Reproductive indices:
See "any other information on material and methods incl. tables".
Offspring viability indices:
See "any other information on material and methods incl. tables".

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
A dosage dependent increase in transient post-dosing salivation was apparent, which was considered to be due to the palatability of the test formulations rather than toxicity. A dosage-dependent increase in the number of animals with reddening of the extremities was also apparent mainly during the early stages of treatment.
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Description (incidence):
No treatment-related deaths were observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Body weight gain and food consumption of males at 1500 mg/kg bw/day appeared to be suppressed when compared with the control group (78 % of controls during weeks 0–5). The body body weight gain for reproductive subgroup females receiving 1500 mg/kg bw/day was reduced during the first week of gestation, after which the values returned to levels comparable with the control.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Body weight gain and food consumption of males at 1500 mg/kg bw/day appeared to be suppressed when compared with the control group (78 % of controls during weeks 0–5).
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
In males, a dosage-dependent reduction in total protein at 750 and 1500 mg/kg bw/day with a slightly elevated albumin/globulin ratio at the top dose was observed.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Some treatment-related effects on haematology were evident (reduction in activated partial thromboplastin time for males at 750 and 1500 mg/kg bw/day, a non-dosage-dependent elevation of alkaline phosphatase levels at 1500 mg/kg bw and 750 mg/kg bw/day, reduced glucose and phosphorous levels at 1500 mg/kg bw/day). Changes in females were limited to a decrease in phosphorous levels and a non-significant increase in alkaline phosphatase level at 1500 mg/kg bw/day.
Endocrine findings:
not specified
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Description (incidence and severity):
There were changes apparent at behavioural testing.
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
The only histological findings related to treatment were the inflammatory/degenerative stomach changes in all treated groups that were considered likely to have arisen due to an irritant effect of the test formulations.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
Mating performance and fertility were unaffected by treatment. For details please refer to box "details on results (P0)".

Details on results (P0)

Summary of effects on reproduction parameters (control, low, mid, high dose):
Females achieving pregnancy: n = 9, 10, 10, 10
Dams with live young born: n = 9, 10, 10, 10
Implants/dam (mean): 15.7, 15.7, 14.1, 15.4
There were no effects on the time to achieve conception, and pregnancy length.

Effect levels (P0)

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
250 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse signs of toxicity were observed in the low dose
Dose descriptor:
LOAEL
Effect level:
750 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
No adverse effects observed.
Histopathological findings:
not specified
Other effects:
not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not examined

Details on results (F1)

Parental treatment had no apparent effect on the offspring to day 4 of age.
Summary of effects (control, low, mid and high dose):
Live pups/dam at birth (mean): 14.8, 14.6, 12.7, 14.0
Live pups/dam at day 4 (mean): 14.6, 14.3, 12.7, 14.0
sex ratio (% m) at birth (mean): 54.2, 52.7, 50.0, 48.5
sex ratio (% m) at day 4 (mean): 54.2, 53.0, 50.0, 48.5
Male pup weight at birth (mean): 6.4, 6.3, 6.6, 6.3
Male pup weight at day 4 (mean): 8.7, 8.5, 9.2, 8.7
Female pup weight at birth: 5.9, 6.0, 6.1, 6.0
Female pup weight at day 4: 8.2, 7.9, 8.6, 8.4
Post-implantation survival index: 95.2, 93.5, 90.0, 94.8
Live birth index: 99.3, 99.4, 100.0, 95.9
Viability index: 98.6, 98.2, 100.0, 100.0

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed at the high dose

Target system / organ toxicity (F1)

Critical effects observed:
no

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
In a repeated dose toxicity study combined with the reproduction/developmental toxicity screening test (OECD 422), the test item diammonium phosphate was administered to male and female CD rats by gavage at dose levels of 0, 250, 750 and 1500 mg/kg bw/day. The NOAEL for parental toxicity was determined to be 250 mg/kg bw/day. No adverse effects were seen on any reproductive or developmental toxicity parameters. Thus, the NOAEL for reproductive/developmental toxicity can be considered to be 1500 mg/kg bw/day.
Executive summary:

In a repeated dose toxicity study combined with the reproduction/developmental toxicity screening test (OECD 422), the test item diammonium phosphate was administered to male and female CD rats (10 females and 5 males/dose group) by gavage at dose levels of 0, 250, 750 and 1500 mg/kg bw/day. Animals were paired 2 weeks after start of treatment. No mortality occurred. Some treatment-related effects on haematology parameters at 1500 and 750 mg/kg bw were evident, and body weight gain was temporarily reduced in the high dose group. Offspring was unaffected by parental exposure. Viability up to day 4 post-partum and macroscopic necropsy showed no effect on the pups. Based on the results, the maternal NOAEL is considered to be 250 mg/kg bw and the NOAEL for reproductive/developmental toxicity is considered to be 1500 mg/kg bw/day.