Reaction mass of dipotassium hydrogen phosphite and potassium dihydrogen phosphite

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013, January-May

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, well conducted

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 422

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Potassium Phosphonate KH2PO3/K2HPO3

IUPAC Name:

Potassium Phosphonate KH2PO3/K2HPO3

Details on test material:

Batch number : 20111216-014
Date of expiry : 13 December 2013
Appearance : White clear fluid solution
Storage conditions : Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Animal supply and acclimatisation
A total of 90 Sprague Dawley rats (45 males and 45 virgin females), 6 to 7 weeks old and weighing 176 to 200 g for males and 151 to 175 g for females, have been ordered from Charles River Italia S.p.A., Calco (Lecco), Italy.
After arrival the weight range for each sex have been determined and the animals have been temporarily identified within the cage by means of a coloured mark on the tail. A health check has then been performed by a veterinarian.
An acclimatisation period of approximately 2 weeks has been allowed before the start of treatment, during which time the health status of the animals has been assessed by thorough observations. Rats considered unsatisfactory have been killed and were appropriate subjected to pathological examination.

Animal husbandry
The animals have been housed in a limited access rodent facility. Animal room controls have been set to maintain temperature and relative humidity at 22°C +/- 2°C and 55%+/- 15% respectively; actual conditions have been monitored, recorded and the records retained. There will be approximately 15 to 20 air changes per hour and the rooms will be lit by artificial light for 12 hours each day.
From arrival to pairing, animals have been housed up to 5 of one sex to a cage, in polisulphone solid bottomed cages measuring 59.5x38x20 cm (Techniplast Gazzada S.a.r.l., Buguggiate, Varese). Nesting material has been provided inside suitable bedding bags and changed at least twice a week.
During mating, animals have been housed one male to one female in clear polycarbonate cages measuring approximately 43x27x18cm with a stainless steel mesh lid and floor (Techniplast – Gazzada S.a.r.l.). Each cage tray holded absorbent material which has been inspected and changed daily.
After mating, the males have been recaged as they were before mating, the females have been transferred to individual solid bottomed cages (Techniplast Gazzada S.a.r.l.) for the gestation period, birth and lactation. Suitable nesting material has been provided and has been changed as necessary.
Drinking water has been supplied ad libitum to each cage via water bottles, except in the case of urinalysis investigations.
A commercially available laboratory rodent diet (4 RF 21, Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI), Italy) will be offered ad libitum throughout the study.
There is no information available to indicate that any non-nutrient substance likely to influence the effect of the test item is present in the drinking water or the diet. Records of analyses of water and diet are kept on file at RTC.
Dated and signed records of activities relating to the day to day running and maintenance of the study in the animal house will be recorded.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Males
Animals have been dosed once a day, 7 days a week, for a minimum of 2 consecutive weeks prior to pairing and thereafter through the day before necropsy.
Dose volumes will be adjusted once per week for each animal according to the last recorded body weight.

Females
Animals will be dosed once a day, 7 days a week, for a minimum of 2 consecutive weeks prior to pairing and thereafter during pairing , post coitum and post partum periods until Day 3 post partum or the day before sacrifice. Dose volumes will be adjusted once per week for each animal according to the last recorded body weight.
During the gestation period, dose volumes will be calculated according to individual body weight on Days 0, 7, 14 and 20 post coitum and on Day 1 post partum. Thereafter individual dose volumes will remain constant.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10 mg/Kg bw
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
100 mg/Kg bw
Basis:
actual ingested

Doses / concentrations 3

Remarks:

Doses / Concentrations:
1000 mg/Kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10 per sex per dose

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOEL oral rat > 1000 mg/Kg bw