Reaction products of triphenyl phosphite and isodecanol (1:2)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

not specified

Principles of method if other than guideline:

This study was performed in compliance with OECD Guideline 422, (1996) and was performed under OECD (1998), and EPA TSCA (1989) Good Laboratory Practice regulations. This study exceeded the OECD 422 study design by following the F1 offspring to weaning.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triisodecyl phosphite

EC Number:

246-998-3

EC Name:

Triisodecyl phosphite

Cas Number:

25448-25-3

Molecular formula:

C30H63O3P

IUPAC Name:

Phosphorus acid, triisodecyl ester

Details on test material:

- Name of test material (as cited in study report): TDP
- Analytical purity: > 99%
- Lot/batch No.: Doverphos 6, Batch 162T041801

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Male and female CD (Sprague-Dawley(SD)) F0 rats were administered TDP orally by gavage at 0, 50, 250 and 1000 mg/kg/day at a dose volume of 5 ml/kg/day in Mazola® corn oil, 10 animals/sex/dose, for 2 weeks of prebreed exposure (males and females), 2 weeks of mating (males and females) and 3 weeks of gestation and lactation each (F0 females).

Details on mating procedure:

After the 2-week prebreed exposure period, animals were randomly mated within treatment groups for a 2-week mating period to produce the F1 generation, with continuing exposure.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

Once a day/7days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 250 and 1000 mg/kg/day
Basis:

No. of animals per sex per dose:

10

Control animals:

other: Needed for CSR report

Examinations

Parental animals: Observations and examinations:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least once daily for F0 males and females until necropsy.

BODY WEIGHT: Yes
- Time schedule for examinations: F0 males and females were recorded weekly during the prebreed period for both sexes and for F0 females during gestation and lactation.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- F0 males and females were recorded weekly during the prebreed period for both sexes and for F0 females during gestation and lactation.

Litter observations:

On the day of birth (postnatal day [pnd] 0), anogenital distance was measured and body weights recorded for all live F1 pups in all litters. F1 litters were culled on pnd 4 to yield as nearly as possible 5 males and 5 females per litter. The culled F1 pups were weighed, euthanized, and necropsied with complete external and visceral examinations. For the remaining F1 pups, survival indices were calculated at least weekly through weaning (pnd 21). In addition, hematology, clinical biochemistry and urinalysis assays were performed at necropsy for 5 randomly selected F0 males. Clinical biochemistry was also assessed for the 28-day females.

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No signs of reproductive or developmental toxicity up to 1000 mg/kd/day

Results: P1 (second parental generation)

Effect levels (P1)

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No signs of reproductive or developmental toxicity up to 1000 mg/kd/day

Results: F1 generation

Details on results (F1)

TDP administered by gavage once daily at 0, 50, 250 and 1000 mg/kg/day to parental F0 CD (SD) rats, 10/sex/group through prebreed, mating, gestation and lactation resulted in essentially no treatment- or dose-related adult F0 parental toxicity at any dose at any time. Reproductive toxicity was not present in F0 males and females. There was also no F1 offspring toxicity observed postnatally through the weanling necropsy. Therefore, the F0 male and female systemic no observable adverse effect level (NOAEL) was at or above 1000 mg/kg/day. The NOAELs for F0 reproductive toxicity during lactation were also at or above 1000 mg/kg/day for males and females.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No signs of reproductive or developmental toxicity up to 1000 mg/kd/day

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

TDP administered by gavage once daily at 0, 50, 250 and 1000 mg/kg/day to parental F0 CD (SD) rats, 10/sex/group through prebreed, mating, gestation and F1 lactation resulted in essentially no treatment or dose related adult F0 parental toxicity at any dose at any time. Reproductive toxicity was not present in F0 males or females. There was also no F1offspring toxicity observed postnatally through the weanling necropsy. Therefore, the F0 male and female systemic no observable adverse effect level (NOAEL) was at or above 1000mg/kg/day for males and females. The NOAELs for F0 reproductive toxicity were observed at or above 1000 mg/kg/day for males and females. The NOAELs for F1 offspring toxicity during lactation were also at or above 1000 mg/kg/day for males and females. (Author)

Executive summary:

DP administered by gavage once daily at 0, 50, 250 and 1000 mg/kg/day to parental F0 CD (SD) rats, 10/sex/group through prebreed, mating, gestation and F1 lactation resulted in essentially no treatment or dose related adult F0 parental toxicity at any dose at any time. Reproductive toxicity was not present in F0 males or females. There was also no F1offspring toxicity observed postnatally through the weanling necropsy. Therefore, the F0 male and female systemic no observable adverse effect level (NOAEL) was at or above 1000mg/kg/day for males and females. The NOAELs for F0 reproductive toxicity were observed at or above 1000 mg/kg/day for males and females. The NOAELs for F1 offspring toxicity during lactation were also at or above 1000 mg/kg/day for males and females. (Author)