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Toxicological information

Neurotoxicity

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990
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 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:
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

Reference
Name:
Unnamed
Type:
Constituent
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.