Tris(2,4-ditert-butylphenyl) phosphite

Neurotoxicity

Description of key information

not neurotoxic to the domestic fowl

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 418 (Delayed Neurotoxicity of Organophosphorus Substances Following Acute Exposure)

Deviations:

yes

Remarks:

No negative control. No preliminary study. No body weight or biochemical parameters measured.

GLP compliance:

no

Limit test:

yes

Species:

hen

Strain:

other: White Leghorn strain

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: VALO" SPF, Lohmann GmbH., Cuxhaven, Germany
- Age at study initiation: 12 months old
- Weight at study initiation: 1.1-2.1 kg- Housing: kept in groups of 5 or 6 (5 females, or 3 males, 3 females) in polyester cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + /-1°C
- Humidity (%): 5 5 +/- 5 %
- Photoperiod (hrs dark / hrs light): 10 hours light cycle

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

Treatment was performed orally by gavage. The test substance was administered twice, initially and after 21 days. TOCP was administered once.

Frequency of treatment:

Treatment was performed orally by gavage. The test substance was administered twice, initially and after 21 days. TOCP was administered once.

Dose / conc.:

2 150 mg/kg bw/day (actual dose received)

Dose / conc.:

6 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

2150 mg/kg 20 female 6000 mg/kg 30 female

Control animals:

no

Details on study design:

Fowls treated with the test substance were observed during a 50-day observation period and those treated with TOCP during a 21-day period.

Observations and clinical examinations performed and frequency:

acute nor delayed systemic symptoms

Details on results:

Signs of acute and delayed toxicityTest substance: Neither acute nor delayed systemic symptoms were observed after the first and second treatinent during the 50 observation days. TOCP; Only slight ataxy and sedation was observed during 2 to 7 days after treatment in those birds that received 600 up to 2150 mg/kg. VJithin 8 to 13 days after administration the male and female birds of all treated groups showed progressive ataxy and deterioration of reflexes, as well as sedation and partially ventral or curved position. These symptoms were more pronounced in the higher dose groups. The male birds of all groups seemed to be less affected than the females.

Dose descriptor:

NOAEL

Effect level:

> 6 000 mg/kg bw/day

Remarks on result:

other:

Conclusions:

The acute oral LD50 of the test substance in hens was found to be greater than 10'000 mg/kg. Doses of 2150 and 6000 mg/kg were administered in the neurotoxicity assay.The oral administration of 2150 and 6000 mg/kg of the test substance dosed twice at an interval of 21 days revealed no toxic symptoms. Histopathological lesions of the nervous system were absent and there was no evidence that delayed neurotoxicity was produced. Therefore, it was concluded that the test substance did not cause neurotoxicity in hens, such as observed with TOCP* included in the test as the reference compound ("positive control").

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

6 000 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

The substance was applied to a total of 50 hens of the White Leghorn strain. The treatment by gavage was performed twice at an interval of 21 days with doses of 2150 (20 hens) and 6000 mg/kg bw (30 hens).

Neither acute nor delayed toxic symptoms were recorded during the 50-day observation period. Histopathological lesions of the nervous system were absent and there was no evidence for delayed neurotoxicity.

Justification for classification or non-classification

There are conclusive but not sufficient data for classification of the test substance with regard to neurotoxicity. The substance is not classified for this endpoint in accordance to the CLP Regulation (EC) No 1272/2008.