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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non standard study, main features reported, standard endpoints missing, high dose, study aiming at neurotoxicity. Also assessed by OECD.

Data source

Reference
Reference Type:
publication
Title:
Evaluation of delayed neurotoxicity and dose-response relationships of phosphate esters in the adult hen.
Author:
Johannsen FR, Wright PL, Gordon DE, Levinskas GJ, Radue RW, Graham PR
Year:
1977
Bibliographic source:
Toxicol. Appl. Pharmacol. 41(2), 291-304

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other:
Deviations:
yes
Principles of method if other than guideline:
Study aimed at investigating neurotoxicity of TPP
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
hen
Strain:
other: Leghorn
Sex:
female

Administration / exposure

Route of administration:
other: oral
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 days (days 1-3, 21-23)
Frequency of treatment:
twice/day
Doses / concentrations
Remarks:
Doses / Concentrations:
2 x 5000 mg/kg bw/day
No. of animals per sex per dose:
9 per group
Details on study design:
Post-exposure period: treatment-free intervals: days 4 to20 and days 24-42

Results and discussion

Results of examinations

Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
OBSERVATION: no effects, neurotoxic response: 0/9 (number positive/number of birds) BODY WEIGHT: not reported MORTALITY: not reported NECROPSY: not reported HISTOPATHOLOGY: no effects

Effect levels

Dose descriptor:
NOAEL
Effect level:
10 000 mg/kg bw/day
Sex:
female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

OBSERVATION: no effects, neurotoxic response: 0/9
(number positive/number of birds)
BODY WEIGHT: not reported
MORTALITY: not reported
NECROPSY: not reported
HISTOPATHOLOGY: no effects

Applicant's summary and conclusion

Conclusions:
The NOAEL is 10000 mg/kg bw /day based on lack of any adverse effects during the study.
Executive summary:

In this non standard study to investigate the neurotoxicity of TPP in hens, 9 hens per group were administered 2 x 5000 mg/kg bw/day TPP by gavage. No neurotoxic effects were observed, and no effects on histopathology. Body weight, mortality, necropsy observations were not reported. Only main features were reported, standard endpoints were missing.