2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs., (4E)-

Endpoint summary

Description of key information

Repeated dose oral 90day (OECDTG408): NOAEL female 6.8 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

6.8 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The study has klimisch code 1.

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 adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Species:

rat

Additional information

Study design oral 90day source substance:

Groups of twelve male and twelve female Alpk:APfSD (Wistar-derived) rats were fed diets containing 0 (control), 65 ,650 or 6500 ppm Aquapel® 364 for at least 90 consecutive days. Clinical observations, bodyweights and food consumption were measured throughout the study. An ophthalmoscopic examination was performed on all animals pre-study and on the control and 6500ppm group in week 12. A functional observation battery, including clinical assessments, measurements of grip strength, time to tail flick, landing foot splay and motor activity were conducted during the last week of the study. Urine samples collected during week 13 were analysed. At the end of the study, the rats were killed and examined post mortem. Cardiac blood samples were taken for clinical pathology, selected organs were weighed and specified tissues were taken for histopathological examination.

 

Results:

Administration of Aquapel® 364 in the diet at 6500ppm resulted in a reduction in bodyweights from weeks 8 and 6 in males and females respectively. Food consumption and utilisation were reduced in both sexes. Red blood cell parameters were reduced and white blood cell counts, alkaline phosphatase, gamma-glutamyl transferase, alanine aminotrans ferase and asp artate aminotrans ferase levels were increased in both sexes and cholesterol was increased in females when compared to controls. Spleen and liver weights were increased in both sexes and kidney weight increased in females. Treatment related inflammatory changes, were observed in a variety of tissues. These changes included foci of

inflammation and histiocytosis. At an administration level of 650ppm Aquapel® 364 in the diet there were similar findings, but of lesser extent to the 6500ppm dose group. In females, a number of red blood cell parameters were reduced and white blood cell counts, cholesterol levels and liver, spleen and kidney weights were increased. In both sexes, there was an increase in alanine aminotransferase, aspartate aminotransferase levels. In males, there were reductions in bodyweight, food consumption and food utilisation in some weeks. Inflammation and histiocytosis were seen there but there was a reduction in the incidence and severity of these changes compared to the top dose group. When Aquapel® 364 was administered in the diet at 65ppm there were no changes of biological or toxicological significance when compared to the controls.

 

Conclusion:

Oral administration of Aquapel® 364 at dietary levels of 6500 and 650 ppm for at least 90 consecutive days resulted in toxicity characterised by lower bodyweights, food consumption and red blood cell parameters and increases in white blood cell counts, liver enzymes changes and spleen and liver weights and inflammation and histiocytosis were seen in a number of tissues. There were no test substance related findings at a dietary level of 65 ppm.

The no observed adverse effect level (NOAEL) for this study was considered to be 65 ppm Aquapel® 364, equivalent to 6.3 and 6.8 mg/kg bodyweight for males and females respectively.

 

Justification for classification or non-classification

Based on the available study results, the substance does not have to be classified and has no obligatory labelling requirement for STOT according to Regulation (EC) No 1272/2008 and its amendments.