Palladium (II) di(4-oxopent-2-en-2-oate)

Endpoint summary

Description of key information

The repeated-dose toxicity of palladium(II) di(4-oxopent-2-en-2-oate) (Pdacac) was assessed in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD TG 422 and in accordance with GLP. Rats (10/sex/group) were given daily oral gavage doses of 3, 10 or 30 mg/kg bw, throughout the pre-mating and mating periods (total 33 days' treatment for males), and (for females), throughout gestation and lactation (total 51 - 63 days' treatment). Two high-dose females died during the study. Males and females in the high-dose group were found to have reduced body weights relative to controls. 

 

The critical adverse effect was hypertrophy of the adrenal cortex, seen in intermediate- and high-dose parental animals of both sexes. A light brown discolouration of the adrenal glands was also seen in some intermediate- and high-dose females, while in intermediate- and high-dose males, the absolute and relative weights of the adrenal glands were increased.

 

On the basis of these effects, the NOAEL for general systemic toxicity in this study was concluded to be 3 mg/kg bw/day (the lowest tested dose), which equates to 1.05 mg/kg bw/day for palladium, based on MWt ratios.

 

No repeated dose toxicity studies by the inhalation or dermal route were identified, or are required.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

3 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Overall, good-quality database which meets REACH Standard Information Requirements.

System:

endocrine system

Organ:

adrenal glands

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

Additional information

No relevant human data were identified.

 

According to REACH Annex VIII (EC 1907/2006), repeated dose toxicity studies only need to be conducted on one species taking into consideration the most appropriate route of administration regarding human exposure. The compound is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure. Similarly, skin contact during production and/or use is expected to be negligible. As the oral route of exposure is considered the most appropriate, repeated dose toxicity studies were not carried out for the dermal or inhalation routes.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
GLP study, conducted according to OECD guidelines, and the only repeated dose toxicity study available.

Justification for classification or non-classification

The critical effect for consideration of classification or non-classification was the increased adrenal weights and accompanying hypertrophy. Adrenal effects of this nature are common and are generally regarded as adaptive rather than adverse. On this basis, no classification for STOT RE is required for this substance.