Triphenylphosphine oxide

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: acute oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: proposed guidelines of the United States Environmental Protection Agency (E.P.A) 163, 81 - 7 Acute delayed neurotoxicity study, published in the Federal Reqister on August 22, 1978, Part II, pages 37362 and 37363

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Triphenylphosphine oxide

EC Number:

212-338-8

EC Name:

Triphenylphosphine oxide

Cas Number:

791-28-6

Molecular formula:

C18H15OP

IUPAC Name:

triphenylphosphine oxide

Details on test material:

- Name of test material (as cited in study report): TPPO
- Physical state: white powder
- Purity: 99.6%

Test animals

Species:

hen

Strain:

not specified

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Graygable Poultry Service, 12 Leech Walk, Bury St Edmunds, Suffolk
- Age at study initiation: >12 months
- Weight at study initiation: 2000-3000g
- Housing: housed in groups in floor pens in a poultry building which was designed to provide a satisfactory range of environmental conditions for this species . The pen size for the LD50 determinations was 2 .4 x 3 .1 m for 30 birds
- Diet (e.g. ad libitum): standard HRC layer diet in meal form obtained from Flowers and Son (Ramsey) Ltd ., Cambridgeshire

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 10 - 27 (mean 21)
- Humidity (%): 52-75 (63)
- Air changes (per hr): ventilation fans were adjusted as necessary
- Photoperiod (hrs dark / hrs light): 7/17

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

VEHICLE
- Concentration in vehicle: 40% w/w

MEAN VOLUME APPLIED: 47.8 mL/ animal

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

once (as 3 doses over a 9-hour period (approximately )), with an observation period of 21 d

Frequency of treatment:

once

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 7400 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

10 females (control), 20 females (TS, two groups)

Control animals:

yes, concurrent vehicle

Examinations

Positive control:

TOCP (500 mg/kg bw)

Results and discussion

Results of examinations

Details on results:

Mortality:
10/20 birds died.

Symptoms:
1/10 birds dosed with TPPO at 7400 mg/kg bw showed grade 1 and 2 ataxia on days 13 and 14, respectively. However, since this bird died on day 15 it is likely that the signs of ataxia observed could be attributed to general weakness. No other birds dosed with TPPO showed any clinical signs of neurotoxicity.
All birds dosed with TOCP at 500 mg/kg showed clinical signs of neurotoxicity, with 3 birds sacrificed with Grade 8 ataxia prior to the termination of the observation period.

Body weight:
Over the post dose observation period (Days 0 to 21) birds dosed with TPPO at 7400 mg/kg showed a group mean bodyweight decrease. This decrease occurred over Days 0 to 14 with a group mean bodyweight increase over Days 14 to 21. Birds dosed with TOCP at 500 mg/kg showed a steady reduction in group mean bodyweight over the post dose observation period. The negative control birds also showed a group mean bodyweight decrease over the post dose observation period but this decrease was smaller than for the other groups of birds .

Food consumption:
Food consumption data were variable but there was evidence of a marked reduction in consumption over Days 1 to 17 for Group 3 birds (TPPO 7400 mg/kg) and Days 1 to 14 for Group 4 birds (TPPO 7400 mg/kg). There was evidence of a small reduction in the food consumption of the birds dosed with TOCP at 500 mg/kg over Days 11 to 21 when compared with Days 1 to 10. Food consumption for the Group 1 birds (Control) was within normal limits, with the exception of the food spillage which occurred over Days 8 to 10 .

Neurotoxic signs:
Signs of neurotoxicity were observed in all birds dosed with TOCP at 500 mg/kg; the first signs being observed on Day 9. Three birds with Grade 8 ataxia were sacrificed prior to the termination of the 21-day observation period.
One bird dosed with TPPO at 7400 mg/kg showed Grades 1 and 2 ataxia on Days 13 and 14 respectively. However since this bird died on Day 15 it is likely that the signs of ataxia observed could be attributed to general weakness . No other birds dosed with TPPO showed any clinical signs of neurotoxicity. No signs of ataxia were observed in any of the negative control birds.

Necropsy:
The most common observation made for the birds dosed with TPPO was the presence of muscular atrophy and three of the birds examined had a distended gall bladder. There was evidence in all groups of birds, including the negative and positive control birds, of pole areas on the endocardium and epicardium ofthe heart.

Histopathology
The morphological grades in the positive control group (TOCP 500 mg/kg) corresponded well with the clinical ataxia grades. The site of maximum damage in this group was the cervical and thoracic spinal cord. There was no evidence of neurotoxicity by TPPO, the morphological findings in these groups being undistinguishable from those in the controls.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 7 400 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: no clinical signs of neurotoxicity observed

Remarks on result:

other: