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Toxicological information

Neurotoxicity

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Description of key information

Neurotoxicity was evaluated in two studies. The results suggest that DBPP does not induce delayed neurotoxicity in chickens.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Species:
hen
Quality of whole database:
Two K2 and K4 study available.

Effect on neurotoxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Effect on neurotoxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Neurotoxicity was evaluated in two studies (Abou-Dania 1987 (supporting study); Abou-Dania 1988 (supporting study)).

In the study of Abou-Donia (1988) the effects of DBPP in chickens on brain neurotoxic esterase (NTE), acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) were investigated. The oral LD50 of di-n-butylphenyl phosphate (DBPP) was determined to be 1863 mg/kg body weight in leghorn hens unprotected against its cholinergic effects. The acute effect of this dose was studied on hen brain NTE, AChE and BuChE 24 h after dosing. While this treatment had no effect on brain AChE, it produced statistically significant inhibition of brain NTE (38% inhibition) and plasma BuChE (70% inhibition). Because it is generally assumed that approximately 75% inhibition of hen brain NTE 24h after dosing is required for an organophosphorous compound to have the potential to produce delayed neurotoxicity, the present results suggest that DBPP does not produce delayed neurotoxicity in chickens. These results, however, are equivocal since the oral LD50 dose of DBPP caused statistically significant inhibition of hen brain NTE and plasma BuChE, enzymes that are sensitive to inhibition by delayed neurotoxic organophosphorous compounds. The positive control, tri-o-cresyl phosphate (TOCP) also caused a statistically significant inhibition of hen brain NTE (87% inhibition) and plasma BuChE (62% inhibition). TOCP did not produce a significant effect on brain AChE activity (11% inhibition).

In another study (Abou-Donia 1987) the potential delayed neurotoxicity of DBPP was investigated in hens. A group of hens treated with TOCP served as a positive control. Although 12 out of the 20 hens treated with one or two oral doses (at a 21-day interval) of the LD50 of DBPP died, none of the hens that survived developed delayed neurotoxicity. The lack of delayed neurotoxicity potential of DBPP was demonstrated by a) the absence of any neurologic dysfunction such as leg weakness, ataxia, or paralysis characteristic of organophosphorous compound-induced delayed neurotoxicity (OPIDN) and b) the absence of neuropathology lesions pathognomonic of OPIDN such as Wallerian-type degeneration reported in the literature (Cavanagh 1973; Abou-Donia and Graham 1978, 1979a,b; Abou-Donia et al. 1983,1986) and seen in positive control hens treated with TOCP.

Justification for classification or non-classification