Dibutyl phosphonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Remarks:

other: range-finding study

Type of information:

other: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

31 August to 14 September, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

NTP Study, very reliable source

Justification for type of information:

Justification for Read Across is provided in Section 13 of IUCLID

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: range-finding study

Deviations:

not applicable

Principles of method if other than guideline:

2.5 mL/kg bw/day of test item in 1 % (v/v) corn oil was administered to groups of 5 male and 5 female Fischer 344 rats via oral gavage for 15 days at doses of 250, 500, 1000, 2000, 3000 mg/kg bw/day, alongside a vehicle control group. Animals were checked two times per day for signs of moribundity and mortality; moribund animals were killed. Initial (day 0) but not final body weights were taken. Necropsy was performed on all animals, except those autolyse/cannibalised.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Source Chemical 01

IUPAC Name:

Source Chemical 01

Test material form:

liquid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: 43 days
- Weight at study initiation: male 116-130 g, females 91-95 g
- Housing: 5 per cage, Polycarbonate cage with Ab-Sorb-Dri hardwood chips
- Diet: Purina Lab Chow, ad libitum
- Water: Acidified with HCl (pH 2.6) tap water; available ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
Not reported.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for use and choice of vehicle: the vehicle was chosen because of the potential for chemical hydrolysis in water.
- Concentration in vehicle: 1% w/w
- Dose (vol): 2.5 mL/kg
- Highest rat dose undiluted: 3000 mg/kg.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analyses for the test item in corn oil were performed on every eighth dose mixture to confirm that the correct concentrations were administered to the test animals. The method of analysis involved a methanolic extraction as a purification step and a gas chromatographic assay as a quantitation step.

Duration of treatment / exposure:

15 days

Frequency of treatment:

15 consecutive days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

2 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5 per sex per doses

Control animals:

yes, concurrent vehicle

Details on study design:

Animals were checked two times per day for signs of moribundity and mortality; moribund animals were killed. Initial (day 0) but not final body weights were taken.

Examinations

Sacrifice and pathology:

Necropsies were performed on all animals, except those excessively autolysed or cannibalised.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

effects observed, treatment-related

Other effects:

not examined

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical signs; mortality

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

All rats receiving 1000, 2000, or 3000 mg/kg/day, and 4/5 males and 2/5 females that received 500 mg/kg, died before the end of the study. Rats receiving 500 mg/kg/day or more were inactive after dosing. There were no dose-related findings at necropsy.

Applicant's summary and conclusion

Conclusions:

NOAEL (sub-acute, rat) = 250 mg/kg bw/day
LOAEL (sub-acute, rat) = 500 mg/kg bw/day (based on mortality)

Executive summary:

Sub-acute toxicity of the substance was evaluated in a dose range finding study. 2.5 mL/kg bw/day of test item in 1 % (v/v) corn oil was administered to groups of 5 male and 5 female Fischer 344 rats via oral gavage for 15 days at doses of 250, 500, 1000, 2000, 3000 mg/kg bw/day, alongside a vehicle control group. Animals were checked two times per day for signs of moribundity and mortality; moribund animals were killed. Initial (day 0) but not final body weights were taken. Necropsy was performed on all animals, except those autolyse/cannibalised.

All animals receiving either 1000, 2000 or 3000 mg/kg bw/day, plus and 4/5 males and 2/5 females receiving 500 mg/kg bw/day, died before the end of the study period. No mortality occurred in the low-dose group receiving 250 mg/kg bw/day. There were no dose-related findings at necropsy. Based on mortality, the NOAEL for sub-acute toxicity may be considered 250 mg/kg bw/day. The findings of this study were used to set the doses for a subsequent sub-chronic toxicity study.