Recommendation from the Scientific Committee on Occupational ...

February 2010
European Commission
Employment, Social Affairs and Inclusion
<strong>Recommendation</strong> <strong>from</strong> <strong>the</strong> <strong>Scientific</strong> <strong>Committee</strong> on Occupational Exposure Limits for diacetyl
The acute oral LD50 of diacetyl in rats has been reported to lie between 3000 and 3400 mg/kg
(Colley et al., 1969). Lower values of 1580 mg/kg in <strong>the</strong> rat, 250 mg/kg in <strong>the</strong> mouse and 990
mg/kg in <strong>the</strong> guinea pig have been reported by NTP (1994). A dermal LD50 of > 5000 mg/kg in
<strong>the</strong> rabbit was also reported by NTP (1994).
2.3. Irritation and corrosivity
2.3.1. Human data
Workers exposed to butter flavouring vapors in popcorn manufacturing facilities have
reported eye, skin and nasal irritation (Kanwal, 2003; Kanwal and Martin, 2003, as reported in
NTP, 2007). Atmospheric concentrations of diacetyl measured in one such facility ranged up
to 98 ppm (Plant A, Table 2, Appendix), while in ano<strong>the</strong>r facility reporting such effects <strong>the</strong>
maximum concentration of diacetyl measured was 1.1 ppm (Kanwal and Martin, 2003).
2.3.2. Animal data
Diacetyl is reported to be a severe skin and eye irritant in rabbits (NTP, 1994).
In a study examining <strong>the</strong> sensory irritation potency of diacetyl using a mouse bioassay model,
a 2-h exposure to diacetyl resulted in concentration-dependent irritation in all parts of <strong>the</strong>
respiratory tract in mice (Larsen et al., 2009). The no-observed effect levels for each effect
measured in <strong>the</strong> mice were above 100 ppm, and <strong>the</strong> authors estimated that initiation of
sensory irritation in humans would occur above 20 ppm. The authors also reported that
repeated exposure to high levels of diacetyl decreased <strong>the</strong> sensory irritation warning signal in
mice, suggesting that <strong>the</strong> irritant effects of diacetyl are particularly insidious (Larsen et al.,
2009).
2.4. Sensitisation
2.4.1. Human data
No irritation was observed after a 48-hour closed-patch test on human subjects, and no
sensitisation reaction resulted <strong>from</strong> maximization testing of 29 human volunteers using a
dilution of 2 percent diacetyl in petrolatum (NTP, 1994).
2.4.2. Animal data
Diacetyl is reported to have sensitising properties in animal studies (Anderson et al., 2007).
Sensitisation potential of diacetal, glyoxal, methyl glyoxal and glycolaldehyde has recently
been assessed using quantitative structure-activity relationship (QSAR) programs (Anderson et
al., 2007). All four compounds were predicted to be sensitisers using Derek for Windows and
NIOSH logistic regression, while TOPKAT 6.2 predicted all compounds to be sensitisers except
for methylglyoxal. The four compounds were also tested in a combined irritancy and local
lymph node assay (LLNA). All compounds except for glyoxal were found to be irritants and all
tested positive in <strong>the</strong> LLNA with EC3 values ranging <strong>from</strong> 0.42 to 1.9% (Anderson et al., 2007).
2.5. Repeated dose toxicity
2.5.1. Human data (inhalation)
Exposure to butter flavouring fumes during food manufacture has been reported to be
associated with <strong>the</strong> development of respiratory disease, characterised by irreversible, fixed
airways obstruction often accompanied by persistent dry cough and shortness of breath
upon exertion. . Several employees have been diagnosed with a serious condition known as
bronchiolitis obliterans (Kreiss et al., 2002; Akpinar-Elci et al., 2004; van Rooy et al., 2007; 2009).
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