Diisotridecyl phenyl phosphite

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

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

Reason / purpose for cross-reference:

reference to same study

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

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

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

Remarks:

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

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

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.

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Clinical signs:

no effects observed

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Reproductive effects observed:

not specified

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.

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:

No effects on reproductive performance or development up to 1000 mg/kg/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Use of data on a closely related analogue, triisodecyl phosphite (TDP), has been selected to represent the reproductive and developmental toxicity of PDiTDP. Based on similar toxicity on other mammalian endpoints it appears appropriate to use TDP repeat-dose toxicity data to read-across to PDiTDP. In addition, the OECD- accepted category approach for the C10 and C13 isoalkyl alcohols, hydrolysis products of TDP and TiTDP, respectively, further supports this read-across approach. See justification document in Section 13.  

 

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.

.

The following information is taken into account for any hazard / risk assessment:

No effects on fertility up to the top dose of 1000 mg/kg.

Short description of key information:

The reproductive toxicity of PDiTDP via the oral route has been read-across from the closely related analogue TDP and based on the following study: TDP showed no signs of reproduction/developmental toxicity in an enhanced OECD 422 reproduction/developmental screening toxicity test at doses up to 1000 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:

The effects on fertility of PDiTDP via the oral route has been read-across from a study conducted with the closely related analogue TDP. The study was conducted according to OECD Guideline 422 and to GLP and is adequately reported. Justification for read across to TDP is provided in Section 13.

Effects on developmental toxicity

Description of key information

The reproductive toxicity of TiTDP via the oral route has been read-across from the closely related analogue TDP and based on the following study: TDP showed no signs of reproduction/developmental toxicity in an enhanced OECD 422 reproduction/developmental screening toxicity test at doses up to 1000 mg/kg bw/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no definitive developmental toxicity studies available on PDiTDP. However, an in vitro gene mutation study in bacteria (Ames test, OECD Guideline 471) of TiTDP, a very close analog, is negative. The results of an in vivo chromosome aberration study in mouse bone marrow (OECD Guideline 474) was also negative. Furthermore, The developmental toxicity of PDiTDP via the oral route has been read-across from the closely related analogue TDP (see discussion under fertility). Based on the available data, PDiTDP is not considered to be a developmental toxicant.

The following information is taken into account for any hazard / risk assessment:

Negative genotoxicity results (OECD 471; OECD 474). No effects seen in a reproductive/development screening toxicity study with the top dose of 1000 mg/kg (read across from TDP).

Justification for selection of Effect on developmental toxicity: via oral route:

Using a read-across approach with the closely related analogue TDP, PDiTDP is not expected to be a developmental toxicant. Justification for read across to TDP is provided in Section 13.

Justification for classification or non-classification

No effects on reproductive performance or development.