Registration Dossier

Administrative data

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

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 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.


Short description of key information:
TPP showed no evidence of effects on fertility at a systemically toxic dose of 40 mg/kg/day in a well conducted OECD 422 study which was extended and studied acquisition of puberty and andrology in F1 offspring at doses up to 15 mg/kg/day.

Effects on developmental toxicity

Description of key information
Mortality and reduced body weight gain were observed at a maternal dose of 40 mg/kg/day TPP in F1 offspring during lactation.  This finding was observed in a well conducted OECD 422 study which extended exposures of F1 offspring to pnd 70.  This finding is considered to be secondary to severe maternal toxicity or of the same nature as the adult toxicity observed at this dose, and is not considered to be indicative of a specific effect by TPP on development.
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.