Diphenyl phosphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

40 mg/kg bw/day

Additional information

Diphenyl phosphonate (DPP) is expected to have similar toxicology to that of triphenyl phosphite (TPP), which is a structurally similar compound and minor constituent in DPP. This relationship is explained more fully in the paper attached in Section 13 of this dossier. TPP was administered by gavage once daily at 0, 5, 15, and 40 mg/kg/day to parental F0 CD® (SD) rats, 10/sex/group, through prebreed, mating, gestation, and lactation and direct dosing to Fl offspring (10/sex/group) from weaning to postpartum day 70 (Tyl, 2004). Treatment with TPP resulted in adult F0 parental toxicity at 40 mg/kg/day, increasing over time (reduced body weights, ataxia, and foot splay). Reproductive toxicity was not present in F0 males or females.

 

F1 offspring in the 40 mg/kg/day group were terminated at pnd 22 due to mortality and reduced body weight gain during lactation. F1 offspring from the other groups were weaned at Day 22 and then treated with TPPi for 7 weeks (until postpartum day 70). For these retained Fl males and females, in-life systemic parameters were unaffected, with acquisition of puberty in both sexes and andrological parameters in adult F1 males also unaffected in the surviving dose groups.

 

Based on these results, the F0 male and female systemic no observable adverse effect level (NOAEL) was 15 mg/kg/day. The NOAELs for F0 reproductive toxicity were at or above 40 mg/kg/day for males and females. The Fl adult male and female systemic NOAEL was also 15 mg/kg/day.

 

The above results from Tyl (2004) are supported by studies of TPP metabolites phenol (2 -generation study by Ryan et al, 2001) and triphenyl phosphate (1 -generation study by Welsh et al, 1987). These studies of TPP metabolites showed no evidence of reproductive toxicity.

TPP was also tested for development toxicity

Effects on developmental toxicity

Description of key information

In a guideline OECD 414 prenatal developmental toxicity study conducted according to GLP, triphenyl phosphite was administered by gavage on gestation days 5 -19 to groups of 25 female rats at dose levels of 0, 15, 40, and 110 mg/kg/day. Overt maternal toxicity, morbidity and mortality occurred at the high dose level of 110 mg/kg/day. Lower body weights and skeletal growth retardation were observed in fetuses at the high dose level, and are considered secondary to maternal toxicity.No treatment related effects were observed in maternal and developmental parameters at dose levels of15 and 40 mg/kg/day. Based on these results, the maternal and developmental NOAELS for triphenyl phosphite are considered to be 40 mg/kg/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

15 mg/kg bw/day

Additional information

TPPi was administered by gavage once daily at 0, 5, 15, and 40 mg/kg/day to parental F0 CD® (SD) rats, 10/sex/group, through prebreed, mating, gestation, and lactation and direct dosing to Fl offspring (10/sex/group) from weaning to postpartum day 70 (Tyl, 2004). Treatment with TPPi resulted in adult F0 parental toxicity at 40 mg/kg/day, increasing over time (reduced body weights, ataxia, and foot splay). Reproductive toxicity was not present in F0 males or females.

 

F1 offspring in the 40 mg/kg/day group were terminated at pnd 22 due to mortality and reduced body weight gain during lactation. F1 offspring from the other groups were weaned at Day 22 and then treated with TPPi for 7 weeks (until postpartum day 70). For these retained Fl males and females, in-life systemic parameters were unaffected, with acquisition of puberty in both sexes and andrological parameters in adult F1 males also unaffected in the surviving dose groups.

 

Based on these results, the F0 male and female systemic no observable adverse effect level (NOAEL) was 15 mg/kg/day. The NOAELs for F0 reproductive toxicity were at or above 40 mg/kg/day for males and females. The NOAEL for Fl offspring effects during lactation were 15 mg/kg/day for males and females. The Fl adult male and female systemic NOAEL was also 15 mg/kg/day.

 

The above results from Tyl (2004) are supported by developmental toxicity studies of TPP metabolites phenol (EU RAR, 2006; NTP, 1983a,b) and triphenyl phosphate (Welsh et al, 1987). These studies of TPP metabolites showed no evidence of developmental toxicity.

Justification for classification or non-classification

Based on data available for TPP and its metabolites phenol and triphenyl phosphate, TPP is not considered to be a reproductive or development toxicant. As such TPP is not classified as a reproductive hazard.