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Administrative data

Description of key information

The potential toxicity of sodium hypophosphite following repeated administration was investigated  according to OECD guideline 422 and EPA 
guideline OPPTS 870.3650.
Sodium hypophosphite is of low toxicity by repeated administration:
The NOAEL was established to 1080 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 080 mg/kg bw/day
Species:
rat

Additional information

Two studies are reported for this endpoint:

The objective of the first study was to determine dose-levels of Sodium hypophosphite to be administered in a combined repeated-dose toxicity study with the reproduction/ developmental toxicity screening test.

The second study, which was chosen as the key study, is the combined repeated dose toxicity study with reproduction/developmental toxicity screening test. This study was performed according to OECD guideline 422 and was conducted in compliance with the principles of Good Laboratory Practices.

In the main study, three groups of 10 males and 10 females were administered Sodium hypophosphite once daily by gavage for 2 weeks before mating, during mating (up to 3 weeks), and, for the females, through gestation until day 5post-partum. The dose-levels selected on the basis of a 2- week range finding toxicity study were 101, 309 and 1080 mg/kg/day. A concurrent vehicle control group received purified water.

Clinical signs and mortality were checked daily and detailed clinical observations were performed weekly. Body weight and food consumption were recorded weekly until mating and then at designated intervals throughout gestation and lactation. A Functional Observation Battery including touch response, forelimb grip strength, pupillary reflex, visual stimulus response, auditary startle reflex, tail pinch response, righting reflex, landing foot splay, rectal temperature and motor activity was performed at the end of the study. Blood and urine samples were taken for analysis of haematology, clinical chemistry and urinalysis at the end of the study.

Males were sacrificed after completion of the mating period and females on day 6 post-partum. Afterwards the designated organs were weighed and gross pathology as well as histopathology were performed.

There were no treatment-related unscheduled deaths during the study and no relevant clinical signs were observed. There were no treatment-related effects on body weight, body weight gain or food consumption at any dose-level. The functional observation battery assessment and hematology and blood biochemistry revealed no treatment-related effects but males from all groups had protein in the urine at a non-dose-related incidence.

There were no treatment-related macroscopic findings and the only effect on organ weights was a lower thymus weight in females treated at 309 or 1080 mg/kg/day which, in the absence of histopathological changes was considered to be of low toxicological significance. Microscopic examination revealed minimal increased epithelial thickness of the forestomach, in males treated at 309 mg/kg/day and in both sexes treated at 1080 mg/kg/day.

This change was considered to be related to treatment with the test item. However, due to the minimal degree of severity of this change compared with the administered dose-level (more than 1000 mg/kg/day), this effect was considered to be non-adverse and in the absence of a similar structure in the stomach from human beings, this change was not considered relevant for human health.

Under these experimental conditions the No Observed Adverse Effect Level (NOAEL) was 1080 mg/kg/day.

Justification for classification or non-classification

According to the criteria laid down in EU regulation (EC) n° 1272/2008 (CLP) and the EU directive 67/548/EEC, sodium hypophosphite is not classified for repeated dose toxicity by oral route.