Specifications

5
2.2.3 Potential Health Effects
A wide variety of health effects have been potentially linked with occupational nitrous oxide
exposure including: reduced fertility, increased incidence of spontaneous abortion, increased
frequency of sister chromatid exchanges (SCE), interference with vitamin B12 metabolism and
audiovisual disturbances. Hoerauf et al. found an increased number of SCE from exposure in
the operating room to an 8 hr TWA of 12.5 ppm. The primary limitation with this study was that
both nitrous oxide and isofluorane were used in the operating room and it is impossible to
determine which was responsible this finding (Hoerauf et al., 1999).
Animal studies conducted in the 1970s and 1980s suggested that nitrous oxide was embryotoxic
and fetotoxic in rats, caused smaller litters, increased incidence of fetal resorption and increased
number of skeletal abnormalities. The main critiques of these studies were the unrealistic
concentrations and duration of exposure the rats were being exposed (for example 24 hrs/day for
5-9 days at 1000 ppm or 15,000 ppm). The exposure levels used were unreasonably high when
compared to levels encountered in occupational settings.
Many studies have found an increased number of SCE in workers exposed to nitrous oxide,
however, the exposure and outcome were often self-reported, had low response rates and
exposure data was lacking in the studies. Questionnaires were often the method used to collect
the data which can lead to possible response and recall bias (Ahlborg et al., 1995). The main
health concern associated with nitrous oxide exposure is an interference with the metabolism of
Vitamin B12. The theory presented by many studies including Suruda et al., 1997, states that the
gas oxidizes the cobalt atom in the Vitamin B12 from Co
I
to Co
II
which inactivates Vitamin
B12dependent enzymes including methionine synthetase and methylmalonyl coenzyme A
mutase. These enzymes are required for Vitamin B12 activity. The Vitamin B12 deficiency is
thought to lead to defective DNA synthesis.
In 1999, a study by Bodin et al. investigated the potential association between shift work and
nitrous oxide exposure and its effects on pregnancy, birth weight and gestational age. This study
used a questionnaire that was sent to the members of the Swedish Midwives Association. The
findings were that nitrous oxide exposure was associated with reduced birth weight and the