Phosphinic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NoAEL (maternal parameters) : 1000 mg/kg/day (OECD guideline 414)
NoAEL ( embryofetal development based on increased slight development) : 300 mg/kg/day (OECD guideline 414)
NoAEL (embryofetal development) : 1000 mg/kg/day (OECD guideline 414)

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 080 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The data from toxicity of sodium phosphinate are used to assess the toxicity of phosphinic acid as it is commercially prepared as the result of pH adjustment of sodium phosphinate salt. Therefore conclusions are the same.

The reproductive toxicity of phosphinic acid was assessed using a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD guideline 422).The study was in compliance with the Principles of Good Laboratory Practice.

Possible toxicological effects likely to arise from repeated exposure on male and female reproductive performance of Sprague-Dawley rats, such as gonadal function, mating behavior, conception, development of the conceptus and parturition, were investigated. Phosphinic Acid was administered orally once a day by gavage (10 animals per sex per treatment group) at dose-levels of 101, 309 and 1080 mg/kg/d for 2 weeks pre-mating, during mating (up to 3 weeks), and for the females through gestation until day 5 post-partum. A control group was included (10 animals per sex).

Clinical signs and mortality were checked once and twice a day respectively 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. Blood and urine samples were taken for analysis of haematology, clinical chemistry and urinalysis at the end of the study. After 15 days of dosing, the females were paired with males from the same dose-level group for mating and gestation was monitored. The females were allowed to litter and rear their progeny until day 5 post-partum. The total litter sizes and numbers of pups of each sex were recorded after birth. Pup clinical signs were recorded daily and pup body weights were recorded on days 1 and 5 post‑partum. Males were sacrificed after completion of the mating period and the females on day 6 post-partum. A complete macroscopic examination was performed with particular attention to the reproductive organs. Afterwards the designated organs were weighed and gross pathology as well as histopathology was performed. Pups sacrificed on day 6 post-partum and those found dead, were carefully examined for gross external abnormalities and a macroscopic post-mortem examination was performed.

There were no treatment-related unscheduled deaths during the study and no relevant clinical signs were observed. There were also no treatment-related effects on body weight or food consumption at any dose-level. Haematology and clinical chemistry revealed no treatment-related effects, while urinalysis showed that males from the exposed groups had protein in the urine in a non-dose-related manner. There were no differences from controls for mating and fertility parameters. Also the mean number of corpora lutea, implantations and the mean number of live born pups were all comparable to the controls. The test item did not exert any effects on pup development in utero and also no effects of treatment on pup survival, clinical signs, sex ratio or body weight performance after birth. There were no treatment-related macroscopic findings and the only observed effect on organ weights was a lower absolute and relative thymus weight in females treated at 309 or 1080 mg/kg/day. For the latter dose level this effect was statistically significant (p<0.05). However this effect could not be associated with any histopathological change.

Consequently, under the experimental conditions the No Observed Adverse Effect Level (NOAEL) for parental toxicity is 1080 mg/kg/day. The NOEL for reproductive performance (mating and fertility) is 1080 mg/kg/day and the NOEL for toxic effects on progeny is 1080 mg/kg/day.

Short description of key information:
NOEL (mating and fertility) = 1080 mg/kg/day (OECD guideline 422)
NOEL (toxic effects on progeny) = 1080 mg/kg/day (OECD guideline 422)

Justification for selection of Effect on fertility via oral route:
GLP guideline study (OECD 422 Guideline, EPA OPPTS 870.3650 Guideline)

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Species:

rat

Additional information

Justification for selection of Effect on developmental toxicity: via oral route:
Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Toxicity to reproduction: other studies

Additional information

The data from toxicity of sodium phosphinate are used to assess the toxicity of phosphinic acid as it is commercially prepared as the result of pH adjustment of sodium phosphinate salt. Therefore conclusions are the same.

The teratogenicity of sodium phosphinate was assessed using a prenatal toxicity study by gavage, to mated female rats from implantation to the day prior to the scheduled hysterectomy (OECD guideline 414). The study was in compliance with the Principles of Good Laboratory Practice. The animals checked daily for mortality and/or clinical signs. Body weight and food consumption were recorded at designated intervals. On day 21 post-coïtum(p.c.), females were sacrificed and submitted to macroscopic post-mortem examination. Hysterectomy was performed and the numbers ofcorpora lutea, implantations, early and late resorptions, and live and dead fetuses were recorded. The foetuses were weighed, sexed and examined for external, soft tissue and skeletal abnormalities.

At termination on day 21p.c., there were 24, 24, 24 and 23 dams with live fetuses in the vehicle control, 100, 300 and 1000 mg/kg/day groups, respectively. There were no clinical observations in the 100 and 300 mg/kg/day groups. At 1000 mg/kg/day, there were a few clinical signs (piloerection and ptyalism) probably due to the taste of the test item. These findings were considered not to be adverse or toxicologically relevant.

 

There were no toxicological significant findings at examination of fetal cartilages [at 300 and 1000 mg/kg/day, the slight but statistically increases in the number of foetuses with cartilage of thoracic vertebrae present (21.0 and 25.8%vs.12.3% in controls, p<0.05 and 0.01, respectively) were treatment-related but considered of non toxicological significance.

At 100 and 300 mg/kg/day, there were no treatment-related variations. At 1000 mg/kg/day, there was an increased number of litters with foetuses with ossification point of the 14^ththoracic vertebra (47.8%vs.8.3% in controls, p<0.01) anda slight increase in the number of foetuses with incomplete ossification of thoracic vertebrae centrum (23.9 %vs.11.7% in controls, p<0.01). While probably treatment-related, these findings were considered to represent slight development variations and to be non-adverse.

At 1000 mg/kg/day, an increase in the number of foetuses with absence of lumbar vertebrae was observed (1.9% vs. 0.0 % in controls). As the incidence was low, not statistically significant and in the absence of other malformations, this finding was considered to be incidental.

On the basis of the results obtained in this study:

The No Observed Adverse Effect Level (NOAEL) for maternal parameters was considered to be 1000 mg/kg/day,

The No Observed Effect Level (NOEL) for embryo-foetal development was considered to be 300 mg/kg/day, based on increased slight development variation (increased incomplete ossifications or increased ossification points in a few foetuses at 1000 mg/kg/day),

The NOAEL for embryo-fetal development was considered to be 1000 mg/kg/day, based on the absence of toxicologically significant effects at this dose level.

 

The test item did not elicit any teratogenic potential.

Justification for classification or non-classification

According to regulation 67-548 EEC and CLP regulation (EC) N° 1272/2008, Phosphinic Acid is not classified as a reproductive and a toxicant and also does not exhibit effects on or via lactation.