4H-3,1-benzoxazine-2,4(1H)-dione

Endpoint summary

Description of key information

oral
subacute: 5 day, rat, increasing doses from 200 to 1013 mg/kg bw/d: No NOAEL identifiable; no mortality, no clinical signs (standardized protocol, according to Lim et al. 1961; BAYER 1970)
inhalation
subacute: 28 day, rat, aerosol: systemic NOEL = 0.0116 mg/L (increased lung and liver weights in the higher dosed females; standardized protocol, according to Niessen et al. 1963; BAYER 1970)
subacute: 5 day, rat, aerosol: No NOAEL identifiable (standardized protocol, according to Niessen et al. 1963; BAYER 1970)

Additional information

oral

An accumulation test was performed in accordance to Lim et al. (1961). Following a standardized protocol, 30 male Wistar rats received increasing doses of the test substance (technical grade) in an aceton/oil 1:10 preparation for five days per gavage, starting with 200 mg/kg bw up to 1013 mg/kg bw on day 5. A recovery period of seven days followed the treatment period. No deaths and no clinical signs of toxicity were observed at any time point. Due to missing test parameters no NOAEL was identified (BAYER 1970).

Inhalation

An subacute dynamic inhalation study was performed in accordance to Niessen et al. (1963) following a standardized protocol. 10 male and 10 female Wistar rats were exposed to an aerosol of 0.0116 or 0.071 mg/L test substance (technical grade; analytical concentration), which was prepared in a DMSO/ Lutrol 1:1 solution, for 4 hours per day, 5 days per week for four weeks. A control group was exposed to the concurrent vehicle, (DMSO/ Lutrol, 1:1). Observations/examinations included behaviour, body weight gain, selected hematological and clinical-chemical parameters, organ weights and gross pathology.

In high dose females, absolute and relative lung weights and relative liver weights were statistically increased. No other changes were noted. A histopathological examination and a recovery period were not carried out. Therefore, the adversity of the effects - and subsequently an adverse effect level - can not be assessed. The NOEL, however, was carefully considered to be 0.0116 mg/L (BAYER 1970).

Another study was performed following the same study design for only 5 days. Here, 10 Wistar rats of both sexes were exposed to an aerosol with a analytical concentration of 0.197 mg/L (corresponding to 1 mg/L nominal conc.). Neither mortality nor clinical signs were observed. Due to missing test parameters no NOAEL was identified (BAYER 1970).