Triethyl phosphate

Neurotoxicity

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

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.	actvity^a	inhibition (%) ^b	actvity^a	inhibition (%) ^b	actvity^a	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
			actvity^a	inhibition (%) ^b	actvity^a	inhibition (%) ^b
Control0	0 h	1, 2, 3			0,75^c
	48 h	1, 2, 3	27,27		0,72
TEP2000	0 h	4 -9			0,86^c
	27,5 h	7	30,38	0
	48 h	6,8	25,24	7	8,69^d	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