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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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

Constituent 1
Reference substance name:
Triisodecyl phosphite
EC Number:
246-998-3
EC Name:
Triisodecyl phosphite
Cas Number:
25448-25-3
IUPAC Name:
tris(8-methylnonyl) phosphite
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:
yes, concurrent vehicle

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)

General toxicity (P0)

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 / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Effect levels (P0)

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

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
no effects observed

Results: F1 generation

General toxicity (F1)

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

Effect levels (F1)

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

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

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.

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:

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