1-Propanaminium, 3,3',3''-[phosphinylidynetris(oxy)]tris[N-(3-aminopropyl)-2-hydroxy-N,N-dimethyl-, N,N',N''-tri-C6-18 acyl derivs. trichlorides

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

Justification for type of information:

In view of the asence of effects to reproductive organs in a 90 day study on this substance and in view of the absence of effects in development studies, further animal work cannot be justifed.
The data refers to the non-pposphated form of the substance that is conisdered to be a metabolite of the substance to be registered

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Administration on gestation days 5 - 19 (14 day period)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Information taken from US EPA review of surrogate substance
Considered reliable by EPA, although primary source not known.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Administration by gavage on days 5 - 19 of gestation in rats

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

The test material is a betaine formed by hydrolysis of the phosphate ester
A justification for read-across is attached.

Species:

rat

Strain:

CD-1

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Treatment from day 5 - day 19 of gestation

Frequency of treatment:

Daily

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

Control

Dose / conc.:

95 mg/kg bw/day (nominal)

Dose / conc.:

286 mg/kg bw/day (nominal)

Dose / conc.:

950 mg/kg bw/day (nominal)

No. of animals per sex per dose:

21 females

Control animals:

yes, concurrent vehicle

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

At top dose level, one animal died and others showed reduced body weights and damage to GI tract.

Mortality:

mortality observed, treatment-related

Description (incidence):

One death in top group; assumed treatment related

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Reduced body weight top dose

Total litter losses by resorption:

effects observed, treatment-related

Description (incidence and severity):

Resoprtions seen at highest dose levels

Dose descriptor:

NOAEL

Effect level:

95 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

clinical signs

Dose descriptor:

NOAEL

Effect level:

286 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reduction in number of live offspring

Developmental effects observed:

no

The reduced litter sizes due to resorptions considered to be related to maternal toxicity effects

Conclusions:

The betaine was tested at up to tolerated treatment levels with reduction in live pups directly related to maternal toxicity.
There were no developmental effects.
Although there is little detail in the reivew document, the EPA considered the data valid in their assessment that there is no apparent developmental toxicity.