Hydrocarbon waxes (petroleum), oxidized, Me esters, barium salts

Endpoint summary

Description of key information

ORAL
NOAEL = 1000 mg/kg/day, 54 days rat male/female, OECD 422, Dhinsa 2005
INHALATION
In accordance with Column 1 of Annex VIII of Regulation (EC) 1907/2006 (REACH), the repeated dose toxicity study required under information point 8.6. should be conducted using the most appropriate route of administration. It is considered justified to omit the repeated dose inhalation toxicity study on the basis of exposure considerations. 
DERMAL
In accordance with Column 1 of Annex VIII of Regulation (EC) 1907/2006 (REACH), the repeated dose toxicity study required under information point 8.6. should be conducted using the most appropriate route of administration. It is considered justified to omit the repeated dose dermal toxicity study on the basis of exposure considerations. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - 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: 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

Oral

The toxicity of the test material was determined in a repeat dose toxicity study, performed according to the standardised guideline OECD 422.

Sprague-Dawley rats (10 per sex per dose) were given 54 consecutive doses of the test material, receiving 100, 300 or 1000 mg/kg/day. The maximum dose level of 1000 mg/kg/day resulted in treatment-related microscopic changes in the kidneys, thyroid glands, and forestomach at all treatment levels. The renal changes observed were considered to be a consequence of protein accumulation exclusive to the male rat. Changes in thyroid glands and forestomach were considered to be minimal and adaptive in nature. The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg/day.

The study was performed in line with GLP and an accepted standardised guideline with a high standard of reporting. However, the study was performed with a structural analogue and so was assigned a reliability score of 2 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material.

The results of this read-across study can be considered to represent a worst case since the test material (Distillates (petroleum), oxidized light) is a shorter chain material and therefore has a greater potential for absorption within the body. The read-across substance can therefore be considered to be potentially more bioavailable than the registered substance, which, due to its very high log Pow value, is anticipated to have only very limited potential for bioavailability.

Inhalation

In accordance with Column 1 of Annex VIII of Regulation (EC) 1907/2006 (REACH), the repeated dose toxicity study required under information point 8.6. should be conducted using the most appropriate route of administration. It is considered justified to omit the repeated dose inhalation toxicity study on the basis of exposure considerations. 

Integrated testing strategies state that determination of the most likely route of exposure needs to take into account not only how the substance is manufactured and handled, including engineering controls and risk management measures, but also the physicochemical properties of the substance.

The nature of the registered substance means that it is not potentially inhalable; the substance has low vapour pressure and therefore is unlikely to be available for inhalation as a vapour. The low water solubility, high molecular weight and the log Pow value of >9.4 obtained for the structural analogue suggest a limited absorption after inhalation.

If any amount of the substance reaches the alveoli, this will be likely phagocytised by macrophages, located into the immune surveillance tissues and broken down in lysososmes and peroxisomes.

Dermal

In accordance with Column 1 of Annex VIII of Regulation (EC) 1907/2006 (REACH), the repeated dose toxicity study required under information point 8.6. should be conducted using the most appropriate route of administration. It is considered justified to omit the repeated dose dermal toxicity study on the basis of exposure considerations. 

Integrated testing strategies state that determination of the most likely route of exposure needs to take into account not only how the substance is manufactured and handled, including engineering controls and risk management measures, but also the physicochemical properties of the substance.

The physical state, high molecular weight and log Pow value of >9.4 obtained for the structural analogue, together with the low water solubility, indicate very low potential for dermal absorption. Similarly to mineral oils, deposition in the stratum corneum is expected to occur slowly; however, the substance is not sufficiently water soluble to partition from the stratum corneum into the epidermis

As dermal absorption cannot be greater than oral absorption, and the estimate of 2% oral absorption is already a worst-case estimate, no dermal absorption of the registered substance is expected to occur.

The available data are considered to be complete and the result determined, 54 day oral NOAEL of 1000 mg/kg bw/day, was taken forward for risk assessment.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The oral route was considered the most appropriate route.
The study was performed in line with GLP and an accepted standardised guideline with a high standard of reporting. The study was performed with a structural analogue and so was assigned a reliability score of 2 in accordance with the criteria for assessing data quality as outlined in Klimisch (1997) and considered suitable for assessment as an accurate reflection of the test material.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation 1272/2008, the test material does not require classification for specific organ toxicity, repeated dose. The effects observed in the main study are not considered to be toxicologically significant and do not indicate any signs of organ dysfunction.