7-[2-(2-hydroxymethylethoxy)methylethoxy]tetramethyl-3,6,8,11-tetraoxa-7-phosphatridecane-1,13-diol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Guideline OECD 422 oral screening study in rats

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The test item was administered by gavage to three groups, each of twelve male and twelve female Wistar Han™:RccHan™:WIST strain rats, for approximately six weeks (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg bw/day. A control group of twelve males and twelve females was dosed with vehicle alone (Polyethylene glycol 400) over the same treatment period and at the same dosage volume. At 1000 mg/kg bw/day there was a clear effect on fertility leading to only a single pregnancy which appeared to be attributable to treatment-related effects on the testes and epididymides. Although pregnancy rate was satisfactory at lower dosages, treatment-related effects were apparent for the testes and epididymides at 300 mg/kg bw/day and the testes at 100 mg/kg bw/day.

A No Observed Adverse Effect Level (NOAEL) for systemic toxicity and for reproduction of the male could not therefore be established.

For females, there were no findings apparent at 300 mg/kg bw/day that were considered to preclude this dosage from being a NOAEL for systemic toxicity or for reproduction.

Effects on developmental toxicity

Description of key information

Guideline OECD 422 screening study in rats

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The test item was administered by gavage to three groups, each of twelve male and twelve female Wistar Han™:RccHan™:WIST strain rats, for approximately six weeks (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg bw/day. A control group of twelve males and twelve females was dosed with vehicle alone (Polyethylene glycol 400) over the same treatment period and at the same dosage volume.

At 300 mg/kg bw/day, post-natal survival between Days 1 to 4 was slightly lower than control, but offspring mortality was restricted to just three litters and overall no association between maternal treatment and post-natal offspring survival was proven. Additionally the mean success rate at assessment of surface righting for the offspring at Day 1 of age was lower than control. However, there was no indication of any effect on fetal body weight gain, which is probably the most accurate indicator of fetal maturity and development. In view of this the NOAEL for the offspring was considered to be at least 100 mg/kg bw/day and probably 300 mg/kg bw/day.

Justification for classification or non-classification

In a Guideline OECD 422 screening study, at 1000 mg/kg bw/day there was a clear effect on fertility leading to only a single pregnancy which appeared to be attributable to treatment-related effects on the testes and epididymides. Although pregnancy rate was satisfactory at lower dosages, treatment-related effects were apparent for the testes and epididymides at 300 mg/kg bw/day and the testes at 100 mg/kg bw/day.

A No Observed Adverse Effect Level (NOAEL) for systemic toxicity and for reproduction of the male could not therefore be established.

For females, there were no findings apparent at 300 mg/kg bw/day that were considered to preclude this dosage from being a NOAEL for systemic toxicity or for reproduction.

The clear NOAEL for the offspring was considered to be at least 100 mg/kg bw/day.

Based on these results, the test item is classified as Category 2 reproductive toxicant according to the criteria described in Regulation (EC) No 1272/2008. Based on the testicular degeneration findings in the OECD 422 screening study, the test item is placed in Group 2, medium potency, and assigned a Generic Concentration Limit of 3.0%.