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Key value for chemical safety assessment

Effects on fertility

Description of key information
No additional information is available.
Effect on fertility: via oral route
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Additional information

Urea phopshate dissociates directly into urea and phosphoric acid in aqueous environment.

Urea

Large quantities of urea are formed naturally in the human body as a consequence of normal protein catabolism. Urea is shown to be essentially without toxicity in the available studies and no effects (organ weight, gross pathology, histopathology) were observed on the reproductive organs of rats and mice exposed to urea at very high dietary levels for 12 months (Fleischman et al, 1980). The level of any primary, occupational or secondary exposure to urea is likely to be insignificant compared to the quantities (20-50 g/day) produced by normal metabolism and present at high concentrations in the blood. It is therefore considered that urea is very unlikely to be a reproductive toxin and testing cannot be justified scientifically.

Diammonium hydrogenorthophosphate (containing the phosphate part like ureaphosphate)

In an OECD 422 study rats (10/sex/dose) were dosed with 250, 750 and 1500 mg/kg bw/day orally via gavage. Males were treated until termination during week 6 of treatment. Doses were administered to the females for two weeks prior to pairing, throughout pairing and gestation until Day 3 of lactation. No effects on reproduction parameters were observed up to the highest dose tested. Therefore, the NOAEL is considered to be1500 mg/kg bw/day.

The two-generation reproduction toxicity study (OECD Guideline 416) was waived based on the following rationale: although the standard requirement at the tonnage band of >1000 tonnes includes a two-generation reproductive toxicity study (OECD 416), the Intellegent Testing Strategy (ECHA Guidance document, Chapter R.7a: Endpoint specific guidance. Section 7.6.6) indicates that if sufficient data exist to permit a robust conclusion on reproductive toxicity then no further testing will be required. The currently available data for reproductive/developmental testing on phosphoric acid include: 1) Negative in vitro mutagenicity genotoxicity evidence (bacterial reverse mutation and in vitro Chromosomal Aberration) suggests a low potential for germ-cell mutagenicity. 2) In an oral gavage study according to OECD 422 guideline (i. e., combined Repeat Dose/Reproductive-Developmental Toxicity test), diammonium hydrogenorthophosphate was administered to rats. No resulting reproductive or developmental effects were identified, nor were overall toxicological effects seen. A No-Observed Adverse Effects Level (NOAEL) for toxicity, reproduction and developmental effects was established at >1500 mg/kg-bw/day. 3) An oral gavage study of monosodium phosphate in mice and rats, similar to OECD 414, showed no apparent effects on nidation (i. e., implantation of a fertilized egg in a uterus) or on maternal or fetal survival. There were no significant skeletal or soft tissue abnormalities relative to sham-treated controls.


Short description of key information:
Urea phopshate dissociates directly into urea and phosphoric acid in aqueous environment. Reliable data available on diammonium hydrogenorthophosphate shows a NOAEL for reproduction toxicity after oral exposure of rats of ≥1500 mg/kg bw/day. The test was performed according to OECD Guideline 422. For urea: It is considered extremely unlikely that occupational, primary or secondary exposure to urea will result in any effects on fertility as the levels of exposure will be insignificant compared to those present in the body as a result of protein catabolism.

Effects on developmental toxicity

Description of key information
Urea phopshate dissociates directly into urea and phosphoric acid in aqueous environment.
Reliable data available on diammonium hydrogenorthophosphate shows a NOAEL for reproduction toxicity after oral exposure of rats of ≥1500 mg/kg bw/day. The test was performed according to OECD Guideline 422. For the developmental toxicity/teratogenicity endpoint, read-across with monosodium phosphate, anhydrous was done based on structural similarities and as shown in the toxicokinetic assessment (as soon as phosphoric acid reaches the blood system, it hydrolysis in phosphate and therefore, cannot become systemically bio-available as such). The 10 days NOAEL for maternal and developmental toxicity, following oral (gavage) exposure, in male/female CD-1 mouse was > or = 370 mg/kg bw/day and in male/female Wistar rats was > or = 410 mg/kg bw/day. The test was performed according to a method similar to OECD Guideline 414.
No standard studies are available for urea. It is considered extremely unlikely that occupational, primary or secondary exposure to urea will result in developmental toxicity as the levels of exposure will be insignificant compared to those present in the maternal and foetal circulation as a result of protein catabolism.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Additional information

Urea phopshate dissociated directly into urea and phosphoric acid in aqueous environment.

Urea:

Large quantities of urea are formed naturally in the human body as a consequence of normal protein catabolism. Urea is shown to be essentially without toxicity in the available studies. The level of any primary, occupational or secondary exposure to urea is likely to be insignificant compared to the quantities (20-50 g/day) produced by normal metabolism and present at high concentrations in the maternal and foetal circulation. It is therefore considered that urea is very unlikely to be a reproductive toxin and testing cannot be justified scientifically.

Diammonium hydrogenorthophosphate (containing the phosphate part like ureaphosphate)

In an OECD 422 study rats (10/sex/dose) were dosed with 250, 750 and 1500 mg/kg bw/day orally via gavage. Males were treated until termination during week 6 of treatment. Doses were administered to the females for two weeks prior to pairing, throughout pairing and gestation until Day 3 of lactation. No effects on developmental parameters were observed up to the highest dose tested. Therefore, the NOAEL is considered to be1500 mg/kg bw/day.

Monocalcium phosphate (containing the phosphate part like ureaphosphate)

The administration of up to 370 mg/kg (body weight) of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls. The NOAEL was > or = 370 mg/kg bw/day for maternal and developmental toxicity. The administration of up to 410 mg/kg (body weight) of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls. The NOAEL was > or = 410 mg/kg bw/day for maternal and developmental toxicity.

Justification for classification or non-classification

Based on the available data and according to the criteria laid down in the CLP Regulation, urea phosphate should not be classified for reproductive toxicity.