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Toxicological information

Neurotoxicity

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Description of key information

In a reliable study, hindlimb stiffness was seen in rats given benzyl butyl phthalate (BBP) in the diet at 3000 mg/kg bw/day for 44 days, but there was no evidence of neuropathological abnormalities on microscopic examination of tissues from the peripheral and central nervous system. The study was performed in compliance with GLP (Bischoff, 1983; Branch, 1982). A study in hens provided no evidence of neurotoxicity with BBP (Monsanto, 1992). Microscopic examination of central and peripheral nervous tissue from several mammalian species collected from a number of repeated-dose and chronic bioassays has also produced no evidence of neuropathology.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
1 500 mg/kg bw/day

Additional information

In a 6-week study, groups of 10 male and 10 female Sprague Dawley rats were given benzyl butyl phthalate in the diet at levels providing about 500, 1500 or 3000 mg/kg bw/day. A control group of 6 males and 6 females received diet only. At the end of treatment, half the animals in each group were subjected to a gross pathology examination and half were sent to another testing facility for neuropathological examination. Stiffness of the hind limbs was seen at 3000 mg/kg bw/day (in 3 males from week 1 and 6 by week 6, and in 2 females during weeks 4 -6), an effect that was apparently reversible once exposure had ceased. Body weight and food consumption were lower in the top two dose groups in both sexes. There were no effects on gross pathology, and no evidence of histopathological abnormalities in tissues from the peripheral and central nervous system (Bischoff, 1983; Branch, 1982).

The EU RAR reports a 42 -day study in which groups of 10 hens were treated orally with BBP (5000 mg/kg bw/day) or tri-o-tolyl phosphate (positive control) for three consecutive days and then again 21 days later. The positive controls showed signs of neurotoxicity within 11 -18 days of dosing, whereas no such effects were seen in the BBP-treated birds (Monsanto, 1992).

Microscopic examination of central and peripheral nervous tissue from several mammalian species collected from a number of repeated-dose and chronic bioassays has also produced no evidence of neuropathology.

Justification for classification or non-classification

The available data are sufficient to conclude that BBP does not need to be labelled for neurotoxicity under the EU CLP regulations.