Diisotridecyl phosphonate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: short-term oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in compliance with the OECD (1998) and EPA TSCA (1989) Good Laboratory Practices Guidance. (Author)

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:

other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

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

Test material information

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).

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

once daily/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

Observations and clinical examinations performed and frequency:

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.

Neurobehavioural examinations performed and frequency:

FUNCTIONAL OBSERVATIONAL BATTERY: Yes
- 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).

Sacrifice and (histo)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.

Other examinations:

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.

Results and discussion

Results of examinations

Behaviour (functional findings):

no effects observed

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Sex:

male/female

Remarks on result:

other: Generation: maternal (migrated information)

2

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Sex:

male/female

Remarks on result:

other: Generation: offspring (migrated information)

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 nervous system or behaviour up to 1000 mg/kg/day.