3,3'-methylenebis[5-methyloxazolidine]

Endpoint summary

Description of key information

No data are available on effects of the substance after repeated dermal and inhalation exposure.
In a 90-Day subchronic gavage study in rats according to OECD guideline 408 (Rajesh 2001) slight effects on body weight gain and alterations in clinical chemistry in males of the high dose group have been detected. These data suggested a LOAEL of 180 mg/kg bw/day. However, concerning clinical chemistry parameters no historical control data of this laboratory were given. The toxicological relevance of other effects was questionable. No local effects in the stomach were found although such effects are expected. These data suggest that the MTD was not reached in this study. Furthermore, pulmonary infection due to Mycoplasma spec. has been detected in all groups including controls. Altogether, this study has limitations. 
In a 2nd 90-Day subchronic gavage study in rats (OECD guideline 408; Leuschner 2002) the test substance induced local effects in the stomach at a dose level of ≥ 60 mg/kg bw. Other effects at the mid and high dose level (% of granulocyes increased, % of lymphocytes decreased), are considered to be a consequence of this chronic ulcerative gastritis & peritonitis. The toxicological relevance of the reduced pupil size detected in males and females of the high dose group is not clear. The dose levels of 0, 20, 60, 180/120 mg/kg bw/day correspond to a concentration of 0, 0.4, 1.2, 3.6/2.4% in corn oil. Effects in the stomach were detected at a concentration of 1.2%.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

20 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

The substance induced local effects in the stomach of rats after repeated administration via gavage at ≥ 60 mg/kg bw (LOAEC 1.2%). The NOAEL is 20 mg/kg bw/day (NOAEC 0.4%).

The implementation of a subchronic oral study in a 2^nd species is scientifically unjustified because mainly local concentration- dependent effects are expected with the substance which have been sufficiently demonstrated. Furthermore, the implementation of a subacute or subchronic dermal toxicity study in rats is scientifically unjustified because of the corrosive properties of the substance.

Inhalative exposure to the substance is not probable, but rather to the hydrolysis product formaldehyde, which is sufficiently investigated. Therefore the NOAEL of 1.2 mg/m³ for formaldehyde will be applied for assessing the risk from inhalation exposure to the constituents of the reaction product.

The NOAELs for formaldehyde reported in oral subchronic or chronic studies are in the same dose range. For all compounds irritation at the site of contact is the main effect. The LOAECs/NOAECs are lower (formaldehyde) than the concentrations of the substance.

Although the data on 2-hydroxypropylamine are of limited validity, there is some indication that the toxic effects of 2-hydroxypropylamine after repeated oral or inhalation exposure occurred at much higher dose levels. They are therefore not relevant for the overall NOAEL. The NOAEL from the 90 day study of 20 mg/kg bw (concentration: 0.4%) may be used for the risk assessment. This NOAEL refers to local effects in the stomach. The NOAEL for systemic effects is 60 mg/kg bw, based on the reduced pupil size at the high dose level.

Chronic studies are available for formaldehyde and these studies indicated local effects at the site of contact.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Justification for classification or non-classification

The effects observed in the valid 90-Day oral toxicity study in rats were limited to the stomach due to the irritating potential of the test substance. This finding is not relevant for the human. Therefore no classification is required.