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

Endpoint summary

Description of key information

oral
LD50 rat: > 6400 mg/kg bw (standardized protocol, comp. to OECD 401; BASF 1971)
LD50 rat: > 2500 mg/kg bw (standardized protocol; BAYER 1970)
LD50 mouse: > 1000 mg/kg bw (standardized protocol; BAYER 1970)
LD50 guinea pig: ca. 500 mg/kg bw (standardized protocol; BAYER 1970)
LD50 cat: > 500 mg/kg bw (standardized protocol; BAYER 1970)
LD50 hen: > 2500 mg/kg bw (standardized protocol; BAYER 1970)
inhalation
LC50 rat, 4 h exposition to dust aerosol: > 5.3 mg/L (analytical; standardized protocol, comp. to OECD 403; BASF 1990) 
inhalation hazard test, rat, 8h exposition to a vapour saturated atmosphere: 0/12 animals died (standardized protocol; comp. to annex of OECD 403; BASF 1971)
dermal
LD50 rat, 7 day exposition, open: > 500 mg/kg bw (standardized protocol; BAYER 1970)

Additional information

There are reliable data from animal studies available to assess the acute oral and inhalative toxicity of the substance.

oral

In a study comparable to OECD test guideline 401 and following a standardized protocol, 200, 1600, 3200 and 6400 mg/kg bw of the substance (purity unknown) were administered per gavage to five male and five female rats. The substance was prepared in an aqueous CMC solution and administered as 10 mL/kg bw volume dose. Animals were observed for 7 days before necropsy. The LD50 is > 6400 mg/kg bw since only one high-dosed male died after 7 days. Dyspnea was the only treatment related clinical sign; necropsy findings were not observed (BASF AG 1971).

Information on acute oral toxicity levels for several laboratory animals were available from a set of studies performed by Bayer AG (1970) following an internal standard protocol. Generally, three doses of the test substance (purity: technical grade) was administered per gavage in an acetone/oil 1:10 preparation to the animals followed by an observation period of 14 days. The LD50 for the animals were as followed: rat > 2500 mg/kg bw (clinical signs were reversible within 2 days); mouse > 1000 mg/kg bw (no clinical signs observed); guinea pig ca. 500 mg/kg bw (2/5 animals of the 500 mg/kg bw treatment died; clinical signs were reversible within 5 days); cat > 500 mg/kg bw (clinical signs were reversible within 1 day); hen > 2500 mg/kg bw (clinical signs were reversible within 2 days). In all cases the given doses represented the highest doses tested.

inhalation

In a limit test according to OECD test guideline 403, five male and female Wistar rats were exposed to a dust aerosol of the test substance (purity 99.8%; mixed with 1% aerosil) for 4 h, using a nose exposure system. Following a standard protocol, animals were observed for 14 days. Body weight and clinical symptoms were recorded. At the end of the observation period, both decedents and survivors were subjected to pathological examination. The analytical concentration of the test atmosphere was 5.3 mg/L, whereas the nominal concentration was 71 mg/L; the MMAD 50% was 3.0 µm. A respirable dust aerosol fraction that might reach the alveolar region of 81 % was obtained. The LC50 is > 5.3 mg/L, as no deaths occurred in the treatment. Treatment related clinical signs (during exposure irregular respiration, accelerated respiration and eyelid closure, attempts to escape; after exposure nose with reddish smear and crusts, fur discoloured with the test substance and urine-contaminated fur) were reversible within one day. Body weight gain was comparable to the historical control data in females and only slightly retarded in males. No necropsy findings were observed (BASF 1990).

Supporting results were provided by a pair of limit tests in which groups of 20 Wistar rats of both sexes and 20 NMRI male mice were exposed to a dynamically produced aerosol atmosphere of the technical grade test substance for 4 hours according to Niessen et al. (1963). The analytical concentrations were 0.166 and 0.156 mg/L for male and female rats, corresponding to 1.0 mg/L nominal concentration, and 0.255, 0.348 and 0.378 mg/L for male rats, female rats and male mice, corresponding to 2.0 mg/L nominal concentration. No mortality was observed, therefore the LC50 for male rats is > 0.255 mg/L, for female rats >0.348 mg/L and for male mice > 0.378 mg/L. Transient reduction of general health was observed in all high dosed animals; low dosed animals were free from symptoms (BAYER 1970).

In an inhalation hazard test comparable to the annex of OECD guideline 403 and following a standard protocol, six male and six female rats were whole-body-exposed to a dynamically produced atmosphere saturated with the volatile parts of the unchanged test substance (purity unknown) for 8 hours. Neither mortality nor clinical signs nor necropsy findings were observed (BASF 1971).

Information on acute inhalative toxicity levels of statically produced test atmospheres for several laboratory animals were available from a set of studies performed by Bayer AG (1970) following an internal standard protocol. The substance (technical grade) was prepared in a DMSO/Lutrol (1:1) solution. Generally, animals were exposed to 0.049/ 0.046 or 0.062/0.130 mg/L analytical concentrations (0.5 and 1.0 mg/L nominal) for 1 and 4 hours, respectively. Additionally, a trial was performed wit 0.01 mg/L analytical concentration (nominal 0.2 mg/L) and an exposure period of 4 hours. Per treatment, 1 rabbit, 5 guinea pigs, 10 rats and 20 mice were used, all of male sex. There were no mortalities and no clinical signs observed.

dermal

A 25% solution of the test substance in an acetone / oil vehicle (1:10) was applied to the shaved dorsal skin of each of 5 male Wistar rats a dose level of 500 mg/kg bw. A paper collar was used for each animals to prevent licking of the applied material. Since the vapour pressure of the substance is very low, the open test condition is considered of low prejudice for the reliability of the test result. The test article was kept in contact with the skin for 7 days. No deaths and no signs of intoxication were observed. LD50 was > 500 mg/kg bw (Bayer 1970).

Justification for classification or non-classification

According to the available test results, there is no indication given for a classification for its acute oral, inhalative and dermal toxicity according to 67/548/EEC and GHS requirements, respectively.