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Neurotoxicity

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Description of key information

Delayed Neurotoxicity of Organophosphorus Substances Following Acute Exposure; Limit test (similar to OECD 418): NOAEL (neurotoxicity):  ≤ 120000 mg/kg bw (total dose): no neurotoxic potential.

Key value for chemical safety assessment

Effect on neurotoxicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
20 000 mg/kg bw/day

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

In the key acute delayed neurotoxicity study IDDPP was administered via gavage to each test animal (10 mature chickens) at a rate of 10000 mg/kg bw, twice daily for 3 consecutive days. The procedure was repeated following a 21-day observation period. The total dosage of IDDPP administered to each chicken was 120000 mg/kg. Positive control birds received a single oral dose of 0.5 g/kg tri-ortho cresyl phosphate (TOCP). Test and control-birds appeared normal throughout the 42-day test period. No signs of neurotoxicity (extreme weakness of legs and wings) were noted. Gross pathological examination of all animals revealed no abnormal tissue-alterations. Histopathologic examination of sections of brain, spinal cord and sciatic nerve revealed no lesions related to treatment with IDDPP. Based on these results, it is therefore concluded that IDDPP did not induce the neuropathologic alterations characteristic of delayed neurotoxicity in the hen, and the NOAEL for neurotoxicityogy was 20000 mg/kg bw/d.

Two supporting studies were available for neurotoxicity. Both were acute, oral, limit tests. In one study 10 hens were dosed with 25000 mg/kg (5000 mg/kg per day for 5 consecutive days) of IDDPP. The hens were observed for 21 days post dose. A second dose was given (20000/kg (5000 mg/kg per day for 4 consecutive days) of IDDPP, and hens observed an additional 21 days. No clinical neurotoxic response was detected during the first and second test period. No mortality occurred. Results from the biochemical method supported the clinical findings: no inhibition of the neurotoxic esterase was detected at 40000 mg/kg. Based on these results, it is concluded that IDDPP did not induce the neuropathologic alterations characteristic of delayed neurotoxicity in the hen, and the NOAEL for neurotoxicity was 5000 mg/kg bw/day.

In the other supporting study, performed similar to OECD 418, 10 mature chickens received 2 doses of IDDPP per day for 3 consecutive days, 10000 mg/kg at each dose. This dose schedule was repeated on Day 21. Ten positive control birds received a single oral dose of 0.5 g/kg tri-ortho cresyl phosphate (TOCP). All, except one, test birds appeared normal throughout the 42-day test period, exhibiting no signs of neurotoxicity. Histological examination of brain, spinal cord and sciatic nerve revealed no evidence of demyelination in any bird treated with IDDPP. Based on these results, it is therefore concluded that IDDPP did not induce the neuropathologic alterations characteristic of delayed neurotoxicity in the hen and the NOAEL for neurotoxicity was 20000 mg/kg.

Justification for classification or non-classification

Based on the available data, there is no evidence of neurotoxic effects for IDDPP. Therefore, based on the EU criteria outlined in 67/548/EEC and 1272/2008/EC IDDPP does not have to be classified with regard to neurotoxicity.