Reaction mass of 2-ethylhexyl diphenyl phosphite and bis(2-ethylhexyl) phenyl phosphite and triphenyl phosphite

Toxicity to reproduction

Administrative data

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Rationale: GLP Guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

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:

yes

Remarks:

This protocol exceeded the OECD 422 study design by following the F1 offspring to adulthood, with continued exposure and assessments of neurologic, immunologic and reproductive structures and functions. The protocol also assessed F0 recovery males, 28-day

Principles of method if other than guideline:

Method: Modified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triphenyl phosphite

EC Number:

202-908-4

EC Name:

Triphenyl phosphite

Cas Number:

101-02-0

Molecular formula:

C18H15O3P

IUPAC Name:

triphenyl phosphite

Constituent 2

Reference substance name:

Triphenyl phosphate

EC Number:

204-112-2

EC Name:

Triphenyl phosphate

Cas Number:

115-86-6

Molecular formula:

C18-H15-O4-P

IUPAC Name:

triphenyl phosphate

Details on test material:

- Name of test material (as cited in study report): TPPi
- Analytical purity: 99.7%
- Lot/batch No.: 237T03101

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Premating exposure period for males (P and F1) as appropriate: 2 weeks
Premating exposure period for females (P and F1) as appropriate: 2 weeks

Details on mating procedure:

Mating period lasted for 2 weeks; gestation and lactation lasted 3 weeks

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

16 weeks

Frequency of treatment:

1/day 7d/wk

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 5, 15 and 40 mg/kg/day
Basis:

No. of animals per sex per dose:

10 animals/sex/dose for 2 weeks of prebreed exposure (males and females); Five additional F0 males per group from the control and 40 mg/kg/day groups were designated as recovery animals and held without dosing for 2 weeks after the F0 male dosing period was completed, to evaluate recovery from any possible treatment-related effects identified in the high-dose group. Additional 28-day females (5/group at 0 and 40 mg/kg/day) and 28-day recovery females (5/group at 0 and 40 mg/kg/day) were also similarly assessed.

Control animals:

yes

Examinations

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of (5/sex/litter as nearly as possible)

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: 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.

GROSS EXAMINATION OF DEAD PUPS:
The culled F1 pups were weighed, euthanized, and necropsied with complete external and visceral examinations.

Postmortem examinations (offspring):

All F0 parental animals, non-selected F1 weanlings and retained F1 adults were necropsied with complete histologic evaluation of 5 selected F0 males and females in the 0 and 40 mg/kg/day groups. Because of extreme toxicity in the F1 offspring at 40 mg/kg/day, no F1 offspring were retained after weaning. Therefore, tissues from 5 F1 males and females per group at 0 and 15 mg/kg/day were examined histopathologically.

Reproductive indices:

For the remaining F1 pups after standardization performed, survival indices were calculated at least weekly through weaning (pnd 21).

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

>= 40 mg/kg bw/day

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

15 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: This value is for F1 toxicity during lacation.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The F0 male and female systemic no observable adverse effect (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 NOAELs for F1 offspring toxicity during lactation were 15 mg/kg/day for males and females. The F1 male and female systemic NOAEL was also 15 mg/kg/day.

Executive summary:

Used for data submission.