Registration Dossier

Administrative data

Endpoint:
immunotoxicity: oral
Remarks:
other: 120 day exposure
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication with basic data given: comparable to guidelines

Data source

Reference
Reference Type:
publication
Title:
Evaluation of immunotoxicity in a subchronic feeding study of triphenyl phosphate
Author:
Hinton DM, Jessop JJ, Arnold A, Albert RH, Hines FA
Year:
1987
Bibliographic source:
Toxicol. Ind. Health 3:71-89

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The primary aim of the study was to investigate the immune system at dietary TPP concentrations of 0, 0.25, 0.5, 0.75, and 1 %; corresponds to approx. 0, 161, 345, 517 and 711 mg/kg bw/day). Only limited data are reported and standard parameters of repeated dose toxicity is missing. The animals were observed for clinical symptoms. Body weights and food consumption were recorded weekly. Immunotoxicity was assessed by measurements of the weights of lymphoid organs, immunohistochemical evaluation of spleen, thymus, lymph nodes, and the humoral response to antigens. The only clinical chemistry parameter investigated was serum proteins.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
98% pure
"stable under the experimental conditions of the feeding study"

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
120 days
Frequency of treatment:
in the diet
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.25, 0.5, 0.75 and 1 %
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
approx. 0, 161, 345, 517 and 711 mg/kg bw/day)
Basis:
other: estimated
No. of animals per sex per dose:
10 males and 10 females per group
Control animals:
yes, plain diet

Results and discussion

Results of examinations

Details on results:
BODY WEIGHT: significant reduction of growth rate in males at 1%
FOOD CONSUMPTION: temporary increase in males, decrease in females
CLIN CHEMISTRY: increased levels of alpha- and beta- globulin only in female resp. male rats. Effects were not dose dependent but similar in all treated groups.
ORGAN WEIGHT: no effects
HISTOPATHOLOGY: expanded immunohistochemical evaluation with the humoral response to a T-lymphocyte dependent antigen (SRBC) and immunohistochemical evaluation of B- and T-lymphocyte regions of the spleen, thymus and lymph nodes was without effect.
NOEL 0.75 %

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
517 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
calculated based on a dietary concentration of 0.75%
Sex:
male/female
Basis for effect level:
other: lower body weight gain seen at 711 mg/kg bw/day
Dose descriptor:
LOAEL
Effect level:
711 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
calculated based on a dietary concentration of 1%
Sex:
male/female
Basis for effect level:
other: lower body weight gain

Applicant's summary and conclusion

Executive summary:

The primary aim of this study was to investigate immunotoxicity. No significant immunotoxic effects were noted for either sex at any of the dose levels tested. The only effects noted were a decreased rate of growth at high levels of TPP and increases in the levels of a- and β-globulins suggestive of increased hepatic activity. The NOAEL for systemic toxicity in this study was 517 mg/kg/day based on reduced body weight gain at the higher dose of 711 mg/kg/day.