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Toxicological information

Neurotoxicity

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Description of key information

In the chicken, a sensitive species for delayed neurotoxicity, triethylphosphate gave no indication of neurotoxicity. After single administration of high doses (rat, mouse, i.p. >= 300 mg/kg; dog oral 250 mg/kg) TEP causes narcosis and a cholinesterase inhibition which is slight compared to other phosphoric esters. Cholineesterase inhibition is detectable in in vitro studies.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Link to relevant study records
Reference
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.
Qualifier:
according to
Guideline:
other: EPA-Guideline: Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic animals, Addendum 10. Revised edition November 1984; U.S. Environmental Protection Agency; Washington, D.C. 20460 (PB 86-108958), § 81-7 (2).
GLP compliance:
yes
Limit test:
no
Species:
hen
Strain:
other: Leghorn
Sex:
female
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
single dose treatment; observation period after application: 2 days
Frequency of treatment:
single dose
Remarks:
Doses / Concentrations:
2000 mg/kg bw.
Basis:

No. of animals per sex per dose:
6
Control animals:
yes
Observations and clinical examinations performed and frequency:
Estimation of movement coordination.
Neurobehavioural examinations performed and frequency:
Estimation of movement coordination. In order to identify ataxia and paresis the animals were forced to move on a surface of 18 m² for appoximately 2-3 minutes.
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
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
Clinical biochemistry findings:
effects observed, treatment-related
Behaviour (functional findings):
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Neuropathological findings:
not specified
Details on results:
see: remarks on results
Basis for effect level:
other: see: Remarks on results
Remarks on result:
not measured/tested
Remarks:
Effect level not specified
Dose descriptor:
other: neuropathy target esterase (NTE)
Effect level:
2 000 mg/kg bw (total dose)
Sex:
female
Basis for effect level:
other: triethyl phosphate caused only a moderate inhibition of NTE at the applied dose of 2000 mg/kg bw
Remarks on result:
other:

Following acute symptoms were observed: apathy, staggering gait, decreased motility, dazed condition, poor reflexes, labored breathing, diarrhea, red-brown colored feces and ruffled feathers

In 2 surviving animals of the NTE Experiment a slight reduction of body weight could be observed.

No gross pathology findings in NTE experimental animals that survived observed.

Inhibition in brain- , spinal cord- and spare nerv-homogenates after single dose application of TEP, respectively vehicle:

     Brain     Spinal cord     Spinal nerve   
  Substance   Dose  Time/h  animal No.  actvitya  inhibition (%) b    actvitya   inhibition (%) b    actvitya    inhibition (%) b
 Control  0  48 h  1, 2, 3  2875    756    119  
 TEP  2000  27,5 h  7  2120  26  420  44  79  34
     48 h  6, 8  1917  33  435  42  55  54

a = nmol Phenyl valerat/min*g tissue

b = Media of individual inhibition

Activity of Cholinesterase and inhibition in brain and blood plasma of hens after single oral application of TEP, respectively vehicle:

 Substance/ dose (mg/kg bw)   time (h)   animal No.  Brain       
Blood Plasma      
   actvitya    inhibition (%) b  actvitya    inhibition (%) b
 Control0  0 h  1, 2, 3      0,75c  
   48 h  1, 2, 3  27,27    0,72  
 TEP2000  0 h  4 -9      0,86c  
   27,5 h  7  30,38  0    
   48 h  6,8  25,24  7  8,69d  0

a = U7g Tissue

b = media of control values for calculation of ChE-inhibition in %.

c = Value before treatment

d = Value to high (reason not detectable

e = kU/l

NTE analysis results:

 Substance  Dose (mg/kg bw)  NTE-inhibition (%)      
     Brain  Spinal Cord Spinal Nerve
 TEP  2000 31   43 47 
Executive summary:

In order to detect a possible potential of a delayed neurotoxicity of TEP, an exploratory study of the effect on NTE (Neuropathy Target Esterase) in adult hens was executed. TEP was administered in a single oral (gavage) dose of 2000 mg/kg bw. This dose is in accordance with the oral LD50 of approximate 2000 mg/kg bw which was tested before (1000 mg/kg bw; 2000 mg/kg bw; 5 animals /dose; 2 animals died in the 2000 mg/kg bw group). in the TEP group following acute symptoms were observed: apathy, staggering gait, decreased motility, dazed condition, poor reflexes, labored breathing, diarrhea, red-brown colored feces and ruffled feathers. In 2 surviving animals (2/6) of the NTE experiment a slight reduction of body weight could be observed. No gross pathology findings in NTE experimental animals that survived could be observed. No relevant decrease of cholinesterase activity in brain (7%) and blood plasma (0%) were observed. Slight decrease of NTE; no evidence of delayed neurotoxicity ( brain 31%; spinal cord 43%; spinal nerve 47%; the effects observed were under the threshold of 80 % which is defined as the lower limit).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Species:
hen
Quality of whole database:
GLP guideline study (EPA-Guideline: Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic animals, Addendum 10. Revised edition November 1984; U.S. Environmental Protection Agency; Washington, D.C. 20460 (PB 86-108958), § 81-7 (2).)

Additional information

Triethyl phosphate gave no indication of neurotoxicity in chicken


Justification for selection of effect on neurotoxicity via oral route endpoint:
The most reliable study was used as key study and for classification.

Justification for classification or non-classification

Based on the available data a classification is not justified