Morpholine

Endpoint summary

Description of key information

The LD50/LC50 values derived from the key-studies were: LD50 (oral, rat) 1900 mg/kg bw,  LD50 (dermal, rabbit) 500 mg/kg bw, LC50 (rat) 8 g/m³.  Based on these results, Morpholine is considered to be harmful following acute oral, dermal or inhalation exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

1 900 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

8 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

500 mg/kg bw

Additional information

Acute toxicity: oral

The acute oral toxicity of Morpholine in the rat was examined in several toxicity studies. In general, oral administration of Morpholine to rats resulted in LD50 values within the range of 1000 to 2000 mg/kg bw (BASF AG, 1969; Shea, 1939; Smyth et al., 1954; Börzsönyi et al., 1981; Huntsman, 1981). Gastrointestinal and nasal haemorrhage were reported as clinical findings following oral Morpholine administration. When Morpholine was administered to 7 male rats at a neutral pH, no deaths occurred at 1000 mg/kg bw (Börzsönyi et al., 1981). In a supporting study on guinea-pigs (Shea, 1939) a lower LD50 of 900 mg/kg bw was observed.

The Huntsman study (1981) indicating LD50=1680 mg/kg bw ) is the key-study here. The BASF study from 1967, where a LD50 of ca.1900 mg/kg bw was derived, has been identified as a second key-study. These studies represent the most reliable study. A reliable source of test material was used and the test was done according to a well described BASF method which was in compliance with the principles of OECD Guideline 401. The same holds true for the Huntsman study.

Acute toxicity: dermal

In the key study on acute dermal toxicity (Smyth et al., 1954), necrosis on the clipped skin of albino rabbits was noted within 24 hours of application of undiluted Morpholine. Mortality observed within 14 days after dermal exposure to Morpholine resulted in an LD50 of 0.5 mL/kg bw. Due to the given specific density of Morpholine (1.0 g/cm³) a LD50 of 500 mg/kg bw was derived. In a supporting study (Shea, 1939), the single dermal exposure of rabbits to undiluted, unneutralized Morpholine resulted in irreversible skin injuries and death of some animals.

Acute toxicity: inhalation

Exposure to Morpholine at vapour saturation concentrations resulted in 100% lethality after 5.5 h (BASF AG, 1967). Irritating and corrosive properties were noted. In studies using lower Morpholine concentrations, Lam & Van Stee (1978) obtained LC50 values of 8.2 and 7.8 mg/L for male and female rats, respectively (exposure period was not specified; Fed. Proc., 37: 679, abstract no. 2459: A re-evaluation of the toxicity of morpholine). Other authors reported no deaths at a three times higher dose level (24 mg/L) after an exposure period of 4 hours (ILO, 1972). 9/10 rats died after a single exposure to 18.1 mg/L for 6 hours (Huntsman, 1981). With regard to other species, reported LC50 values for mice are consistently in the range of ca. 5 - 7 mg/L (Lam and Van Stee, 1978). Based on these findings and using a conservative approach (here: reflecting the results of Lam & Van Stee, 1978), a LC50 value of ca. 8.0 mg/L for rat is postulated and used for further calculations.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

Based on the results for acute oral (LD50 rat ca. 1900 mg/kg bw), acute dermal (LD50 rabbit 500 mg/kg bw) and inhalation toxicity (LC50 ca. rat 8 mg/L) morpholine is classified as follows: acute toxicity: cat. 4, H302, harmful if swallowed, cat. 3, H311, toxic in contact with skin, and cat. 3, H331, toxic if inhaled (according to Regulation 1272/2008/EC).