Registration Dossier

Administrative data

Description of key information

An OECD 422 modified test was carried out with triisodecyl phosphite used for read across. CD rats were administered the test item by ingestion and showed no treatment related toxicity effects up to 1000 mg/kg bw/d. Moreover, no effects were seen is any of the acute studies by any of the routes, even for Phosphorous acid, tri-C12-14-alkyl esters in the acute oral study. Additionnaly no adverse systemics effects were oserved in the OECD 414 up to 1000 mg/kg bw/d.

For these reasons, it is considered not relevant to use other animals for testing Phosphorous acid, tri-C12-14-alkyl esters by inhalation or dermal route and also for testing further repeated exposure.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
quoted Klimlisch 1, then quoted 2 for read across approach
Justification for type of information:
see Read-across justification attached.
Reason / purpose:
read-across source
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
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.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Other 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.
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
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
Critical effects observed:
not specified
Conclusions:
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

An OECD 422 modified test was carried out with triisodecyl phosphite used for read across. CD rats were administered the test item by ingestion and showed no treatment related toxicity effects up to 1000 kg/kg bw/d. Moreover, no effects were seen is any of the acute studies by any of the routes, even for Phosphorous acid, tri-C12-14-alkyl estersi n the acute oral study. No classification for target organ toxicity is then required for Phosphorous acid, tri-C12-14-alkyl esters.