Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

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
Justification for type of information:
see Read-across justification attached.

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
U.S. HIGH PRODUCTION VOLUME (HPV) CHEMICAL CHALLENGE PROGRAM ROBUST SUMMARY Phosphorous acid, triisodecyl ester (CAS# 25448-25-3)
Author:
General Electric Company on behalf of the Phosphite Producers HPV Consortium and Phosphite Manufacturers Consortium
Year:
2001
Bibliographic source:
US Environmental Protection Agency, HPV Information System
Reference Type:
secondary source
Title:
Unnamed
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
exceeded OECD 422 by following the F1 offspring to weaning
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Doverphos 6, Batch 162T041801
Purity: > 99%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female CD (Sprague-Dawley(SD)) F0 rats, no other detail given

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
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:
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)
Frequency of treatment:
daily
Details on study schedule:
rats were dosed 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).
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 250 and 1000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
10 per sex per dose

Examinations

Parental animals: Observations and examinations:
Body weights and feed consumption for the F0 males and females were recorded weekly during the prebreed period for both sexes and for F0 females during gestation and lactation.
Clinical signs were recorded at least once daily for F0 males and females until necropsy.
Functional Observational Battery (FOB) including home cage observations, handling observations, open field observations, sensory and neuromuscular observations and physiological observations, was performed on all initial animals once during quarantine and at least once per week for F0 animals during prebreed, mating (both sexes), gestation and lactation (F0 females).
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.
Five F0 males and five F0 females per dose group were evaluated for auditory function, motor activity, and assessment of grip strength prior to necropsy.
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.
Postmortem examinations (parental animals):
All F0 parental animals were necropsied with complete histologic evaluation of 5 selected males and females in the 0 and 1000 mg/kg/day groups.

Postmortem examinations (offspring):
The culled F1 pups were weighed, euthanized, and necropsied with complete external and visceral examinations.
Offspring viability indices:
For the remaining F1 pups, survival indices were calculated at least weekly through weaning (pnd 21).

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

No systemic toxicity was shown at any dose at any time.

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: clinical signs; mortality; body weight; food consumption; haematology; clinical chemistry; urinalysis; gross pathology; organ weights; histopathology; FOB

Results: F1 generation

Details on results (F1)

No reproductive toxicity was shown in the offspring generation.

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: body weight and external and visceral examination

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the test conditions, 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.
Executive summary:

Triisodecyl phosphite 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.