Corn oil (Zea mays, Gramineae), peroxidised

Endpoint summary

Description of key information

Oral NOAEL (male, females) >= 1000 mg/kg bw/day (OECD 422, GLP)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The general toxicity of peroxidised corn oil was evaluated in rats by oral route in one subacute toxicity study performed according to OECD 422 and in compliance with GLP. This study was scored as validity 1 according to Klimisch criteria and therefore was selected as the Key study.

 

In a subacute toxicity study (OECD 422, GLP, 2011) peroxidised corn oil (in olive oil as vehicle) was administered to 12 Wistar rats/sex/dose in by gavage at dose levels of 0 (olive oil), 100, 300 and 1000 mg/kg bw/day. In the control and high dose groups, satellite animals were included (6 per sex and group) to provide information about reversibility of toxicological findings.

Females were treated 14 days before mating, 14 days during mating, 22-24 days during gestation and 4 days during lactation. Males were treated 56 days.

There were no test article-related deaths of animals during the study. All animals lived through observation period without important visible signs of intoxication. Neither change of health nor negative reactions were registered in the satellite animals. The test article was very well tolerated by animals of all dose groups.

The body weight of all animals moderately increased. No significant differences were noted between body weight animals of the control and all dose groups during treatment and recovery period.

The food consumption in males and females of all dose groups was similar to the control group.

No test article related effects on the haematology and blood coagulation parameters were observed.

No differences in clinical chemistry parameters which could definitively be attributed to the administration of the test article were found. After recovery period, no relevant differences were found in clinical chemistry parameters.

No significant changes against normal physiological levels were detected in urine of males.

The significant decrease of liver relative weight found in females of medium and high dose groups versus control could be related to the effect of the test article. Historically, it is not uncommon to see the relative weight of liver increased in treated animals versus controls. Also, no significant differences were observed in males or between recovery groups (high dose group and control). However, the effect of treatment cannot be excluded. However, no similar changes were seen in males.

Peroxidised Corn Oil administered at doses up to 1000 mg/kg bw/day caused neither treatment-related deaths of animals nor visible treatment-related signs of intoxication. Test article did not cause pathological and histopathological changes in organs and tissues of rats.

 

The NOAEL for systemic toxicity in males and females was concluded to be 1000 mg/kg bw.

 

No sub-acute or sub-chronic repeated dose toxicity studies are available for dermal or inhalation route. However testing is waived based on the following justification: a sub-acute study is available for the oral route. According to Reach regulation, Annex VIII, column 2 adaptations, Section 8.6.1, only one route of exposure should be tested for repeated dose toxicity.

 

These dermal and inhalation studies can be waived based on column 2 adaptation (Reach regulation, Annex VIII, section 8.6):

 

- Testing by the dermal route is not appropriate, as the physicochemical (high molecular weight, high log Kow, and low water solubility, limiting the rate of dermal penetration) 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). In addition, OECD testing guideline 422 recommends that the test substance is administered orally (unless other routes of administration are considered more appropriate).

 

- 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 the absence of signs of toxicity up to the highest dose of 1000 mg/kg bw/d administered in rats by gavage during 28 days, no classification for repeat-dose toxicity is warranted according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.