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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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)
Version / remarks:
Version: 1996
See: Principles of method
Deviations:
yes
Remarks:
exceeded OECD 422 by following the F1 offspring to weaning
Principles of method if other than guideline:
The study exceeded the OECD 422 guideline design by extending dosing of F0 females through Day 21 of lactation. The original study design included evaluation of 28 day exposure in females (to correlate with 28 day exposure in males), male and female recovery groups, and extended post weaning evaluation (70 days) in F1 offspring. The final study report contains all sections required by the OECD 422 guideline (1996), including data collected on the FO parental animals and on the Fl offspring to their weaning on pnd 21 (an extension beyond the specified termination on pnd 4 in the OECD 422 [1996] testing guideline). The data collected on the 28-day females, the recovery males and females, and on the F1 offspring animals after weaning were collected as initially specified in the protocol but were not included in the study report. The data not reported (and wet tissues, blocks and slides not processed or examined) were retained in the study records and archived with the study upon the submission of the final report.
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 oral exposure:
Rats were administered Triisodecyl phosphite (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).
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).
Therefore:
F0 males were exposed 28 days
F0 females were exposed until 10 weeks (14 days prebreed, mating, gestation, lactation through pnd 21).
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Remarks:
Basis: actual ingested
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Remarks:
Basis: actual ingested
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Remarks:
basis: actual ingested
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Remarks:
basis: actual ingested
No. of animals per sex per dose:
10 per sex per dose

Examinations

Observations and examinations performed and frequency:
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.
Sacrifice and pathology:
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.
The culled F1 pups were weighed, euthanized, and necropsied with complete external and visceral examinations.
Other examinations:
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. 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 of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No systemic toxicity was shown at any dose at any time.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
clinical biochemistry
urinalysis
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
other: Functional Observational Battery (FOB)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the test conditions, the F0 male and female systemic no observable adverse effect level (NOAEL) was at or above 1000mg/kg/day for males and females.
Executive summary:

Triisodecyl phosphite (TDP) was tested for repeated toxicity according to the OECD 422 test guideline

Triisodecyl phosphite (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 F1 offspring toxicity observed postnatally through the weanling necropsy. Therefore, the F0 male (28 days) and female (8 - 9 weeks) systemic no observable adverse effect level (NOAEL), including neurotoxicity, was at or above 1000 mg/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.