Reaction mass of Octadec-9-en-1-yl ammonium di-n-hexyl phosphorodithioate and Octadec-9-en-1-yl ammonium mono- and di-butylphosphate

Endpoint summary

Description of key information

Wistar rats were treated with 434 -280 -4 for 28 -consecutive dats or until termination by oral gavage at dose levels of 0, 30, 100 and 300 mg/kg/day.

Intercurrent deaths

Thehighest dose of 300 mg/kg /day resulted in deaths and moribundity. Two females were found dead on study day 11. Furthermore, two males and one female were killed in extremis on day 10. Remaining males and females treated at 300 mg/kg/day (main and recovery groups) were sacrificed for humane reasons on day 11. The control recovery groups were sacrificed on the same day for sceintific reasons.. Clininical signs in these animals consisted of emaciation, hunched posture, breathing rales, pilo-erection, salivation, chromodacryorrhoea, lean appearance, squeakig, lethargy, ncoordinated moverments, yellow discolouration of the skin, pale ears, dehydration, ptosis and hypothermia. Reduced body weight gain and food intake was also noted. At the clinical labortaory investigations several findings relating to emaciation and the poor condition of the high dose animals were found.

Animals surviviing until planned sacrifice

At 100 mg/kg/day at the terminal sacrifice, histiocytosis in the mesenteric lymph node was noted. In the smalll intestine, foamy macrophages in the villi at minimal to moderate degree were noted in several rats at 100 mg/kg/day at terminal sacrifice. These effects were also accompanied by higher white bllod cell counts and hihger neutrophil counts in both sexes. Reduced body weight gain adn food intake was also noted in males at 100 mg/kg/day. Higher platelet counts and higher red blood cell counts were considered to be a secondary effect, probably caused by stimulation of the bone marrow. Chromodacryorrhoea wa pbserved during the last week of the treatment in two females att 100 mg/kg/day.

At 30 mg/kg/day higher nuetrophil counts were noted in males, but were note accompanied by higher whire blood cell counts. Higher white blood cell counts were noted in females, but were not accompanied by higher neurotphil counts. Additionally, no supportive effects were found at the macroscopic or microscopic examinations; therefore these changes were not regarded as toxicologically relevant.

No inhibition of cholinesterase was found at any dose level. Plasma cholinesterase was inhibited by 51% and 69% in males and females at 300 mg/kg/day, by 9% and 46% in males and females at 100 mg/kg/day and 5% and 12% in males and females at 30 mg/kg/dat and in males at 100 mg/kg/day was not considered to be significant.

From the results presented in the report a definitive No Observed Adverse Effect Level (NOAEL) for subchronic toxicity for 434 -280 -4of 30 mg/kg/was established.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

30 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Wistar rats were treated with EC434 -280 -4 for 28 -consecutive dats or until termination by oral gavage at dose levels of 0, 30, 100 and 300 mg/kg/day.

Intercurrent deaths

Thehighest dose of 300mg/kg /day resulted in deaths and moribundity. Two females were found dead on study day 11. Furthermore, two males and one female were killed in extremis on day 10. Remaining males and females treated at 300 mg/kg/day (main and recovery groups) were sacrificed for humane reasons on day 11. The control recovery groups were sacrificed on the same day for sceintific reasons.. Clininical signs in these animals consisted of emaciation, hunched posture, breathing rales, pilo-erection, salivation, chromodacryorrhoea, lean appearance, squeakig, lethargy, ncoordinated moverments, yellow discolouration of the skin, pale ears, dehydration, ptosis and hypothermia. Reduced body weight gain and food intake was also noted. At the clinical labortaory investigations several findings relating to emaciation and the poor condition of the high dose animals were found.

Animals surviviing until planned sacrifice

At 100 mg/kg/day at the terminal sacrifice, histiocytosis in the mesenteric lymph node was noted. In the smalll intestine, foamy macrophages in the villi at minimal to moderate degree were noted in several rats at 100 mg/kg/day at terminal sacrifice. These effects were also accompanied by higher white bllod cell counts and hihger neutrophil counts in both sexes. Reduced body weight gain adn food intake was also noted in males at 100 mg/kg/day. Higher platelet counts and higher red blood cell counts were considered to be a secondary effect, probably caused by stimulation of the bone marrow. Chromodacryorrhoea wa pbserved during the last week of the treatment in two females att 100 mg/kg/day.

At 30 mg/kg/day higher nuetrophil counts were noted in males, but were note accompanied by higher whire blood cell counts. Higher white blood cell counts were noted in females, but were not accompanied by higher neurotphil counts. Additionally, no supportive effects were found at the macroscopic or microscopic examinations; therefore these changes were not regarded as toxicologically relevant.

No inhibition of cholinesterase was found at any dose level. Plasma cholinesterase was inhibited by 51% and 69% in males and females at 300 mg/kg/day, by 9% and 46% in males and females at 100 mg/kg/day and 5% and 12% in males and females at 30 mg/kg/dat and in males at 100 mg/kg/day was not considered to be significant.

From the results presented in the report a definitive No Observed Adverse Effect Level (NOAEL) for subchronic toxicity for EC 434 -280 -4 of 30 mg/kg/was established.