Tributyl phosphate

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: guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Reference 2

Reference Type:

publication

Title:

Neurotoxicity studies in Sprague-Dawley rats with tributyl phosphate

Author:

Healy C, Beyrouty P, Losos G, Broxup BR

Year:

1992

Bibliographic source:

Toxicologist 12, 324 (1992)

Reference 3

Reference Type:

publication

Title:

Acute and subchronic neurotoxicity studies with tri-n-butyl phosphate in adult Sprague-Dawley rats

Author:

Healy CE, Beyrouty PC, Broxup BR

Year:

1995

Bibliographic source:

Am Ind Hyg Assoc J 56, 349-355

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.6050 (Neurotoxicity Screening Battery)

Principles of method if other than guideline:

Groups of 12 male and 12 female Sprague-Dawley rats were treated, by gavage, with tributyl phosphate (TBP) on a single occasion at dose levels of 100, 325 or 1000 mg/kg and then observed for 14 days. A control group was handled in an identical manner, except is was treated with the vehicle, corn oil, at the same dosage volume (10 ml/kg). The animals were examined using a functional observation battery (FOB) pre-study, at approximately 1 hour, 6 hours and 24 hours postdosing, and on observation days 7 and 14. Motor activity testing was conducted pre-study and on days 0 (approximately 11 hours following treatment), 7 and 14. Animals were subjected to a gross pathological examination at the completion of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tributyl phosphate

EC Number:

204-800-2

EC Name:

Tributyl phosphate

Cas Number:

126-73-8

Molecular formula:

C12H27O4P

IUPAC Name:

tributyl phosphate

Details on test material:

tributyl phosphate was received from FMC Corp.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

single treatment/ 14 d observation period

Frequency of treatment:

single treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 325 or 1000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

12 males and 12 females

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: NOAEL concerning neurotoxicity (single treatment/ 14 d observation period)

Remarks on result:

other:

Any other information on results incl. tables

no data

Applicant's summary and conclusion

Executive summary:

Groups of 12 male and 12 female Sprague-Dawley rats were treated, by gavage, with tributyl phosphate (TBP) on a single occasion at dose levels of 100, 325 or 1000 mg/kg and then observed for 14 days. A control group was handled in an identical manner, except is was treated with the vehicle, corn oil, at the same dosage volume (10 ml/kg). The animals were examined using a functional observation battery (FOB) pre-study, at approximately 1 hour, 6 hours and 24 hours postdosing, and on observation days 7 and 14. Motor activity testing was conducted pre-study and on days 0 (approximately 11 hours following treatment), 7 and 14. Animals were subjected to a gross pathological examination at the completion of the study.

Dosages of 325 and 1000 mg/kg resulted in transient clinical changes and 1000 mg/kg resulted in transient decreases in male body weights, forelimb gripstrengh and motor activity levels for both sexes. The pattern of effects seen was attributed to an acute, non-specific toxicity without apparent neurotoxicity. No gross pathological findings were seen indicative of a treatment-related effect.