Neodymium di(2-ethylhexyl) phosphate

Endpoint summary

Description of key information

Oral route (rat, gavage, 28 days):
- No Observed Adverse Effect Level for local effects (NOAEL local) is less than 150 mg/kg/day based on microscopic findings in the forestomach.
- No Observed Adverse Effect Level for systemic effects (NOAEL systemic) is = 450 mg/kg/day based on systemic effects.

Additional information

A repeated toxicity study is available on neodymium tris (di-2-ethylhexylphosphate). This study was performed according to OECD guideline n° 407 (and EU B.7 and US/EPA/OPPTS 870.3050) and in accordance with GLP. This study was thus scored as validity 1 according to Klimisch criteria and then was selected as the Key study.

In a subacute toxicity study scored as validity 1 according to Klimisch criteria (OECD guideline 407, GLP, CIT report No.32953 TSR, 2007), neodymium tris-(di-2-éthylhexyl phosphate) was administered daily to 5 Sprague-Dawley rats/sex/dose by gavage at dose levels of 0, 150, 450 or 1000 mg/kg/day as a suspension in corn oil.

During the study, animals were checked regularly for mortality and clinical signs, and body weights and food consumption were recorded.

Hematological and blood biochemical investigations as well as a Functional Observation Battery (FOB), including motor activity, were performed on all animals at the end of the treatment period.

Estrous cycles of the females were monitored for approximately 1 week prior to sacrifice.

At the end of the 4-week exposure period, the animals were killed and were submitted for a macroscopic and microscopic post-mortem examination. In addition, sperm analysis (epididymal and testicular sperm counts, sperm motility and morphology) was performed for each male and a detailed and careful microscopic examination of one testis and one ovary was performed for each animal.

 

No treatment-related of toxicological relevance was observed concerning the following effects: mortality (there were no unscheduled deaths), clinical signs, body weight and body weight gain, food consumption and blood chemistry. There were no treatment-related effects on sperm motility or morphology or on epididymal or testicular sperm count. All females had normal estrous cycles. There was no macroscopic finding except in the forestomach of one female treated at 450 mg/kg bw/day.

The males treated at 1000 mg/kg bw/day had a smaller landing foot spay than control but there were no other effects observed in the Functional Observation Battery (FOB) and motor activity and no effects were observed in the males from others treated groups and in females from all treated groups., The mean white blood cell count of both males and females treated at 1000 mg/kg bw/day was lower than concurrent control values. This decrease was observed for all the types of white blood cell but achieved statistical significance for male basophile levels (p<0.05). No effects on haematology parameters were observed in males and females from the others treated groups. There was a statistically significant increase in absolute and relative liver weights in male treated at 1000 mg/kg bw/day but no relevant differences to control values were observed in males from the other treated groups and females from all groups,

Multifocal epithelial cells hyperplasia of the forestomach with or without erosion, hyperkeratosis, squamous crust and submucosal inflammation were observed at a dose-related increased incidence and at a dose-related increased severity at all dose-levels in the animals of both sexes. This finding is considered to be related to treatment, although it is probably a local effect related to the administration of the test item by gavage.

 

Under the experimental conditions, it was therefore considered that:

- the No Observed Adverse Effect Level for local effects (NOAEL local) was less than 150 mg/kg/day based on microscopic findings in the forestomach.

- the No Observed Adverse Effect Level for systemic effects (NOAEL systemic) was 450 mg/kg/day based on the systemic effects observed (haematology, organ weight and one FOB parameter).

Based on this study, no classification for repeat-dose toxicity is warranted, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.

 

- Testing by the dermal route is not appropriate, as the physicochemical (very low water solubility) and toxicological properties (no sign of toxicity by acute exposure at 2000 mg/kg bw in rats) do not suggest potential for a significant rate of absorption through the skin (skin absorption < oral absorption).

- Testing by the inhalation route is not appropriate because exposure of humans via inhalation is unlikely; handling of the registered substance does not produce vapour, aerosols or droplets.

Justification for classification or non-classification

 Based on the classification criteria of Annex VI Directive 67/548/EEC or UN/EU GHS, and given data available with neodymium tris-(di-2-éthylhexyl phosphate, no classification for repeat-dose toxicity is warranted.