Acrylonitrile

Endpoint summary

Description of key information

Rongzhu et al. (2005) assessed the neurobehavioural effects of acrylonitrile in exposed Chinese workers. The WHO-recommended Neurobehavioural Core Test Battery (NCTB) was used to assess 81 workers in an acrylonitrile-monomer plant and 94 workers in an acrylic fibres plant. Acrylonitrile workers reported increased tension, depression, anger, fatigue and confusion on the Profile of Mood States. Performances in the Simple Reaction Time, Digit Span, Benton Visual Retention and Pursuit Aiming II were also poorer among exposed workers compared to unexposed workers. Some of these poor performances in tests were also related to exposure duration. The authors acknowledged that there were no firm estimates of exposures, and the data available was from a very short time span (1997 -1999). The examiners were reportedly well trained, but the authors could not rule out the possibility that examiner drift could be responsible for the group differences observed. The authors conclude that given the findings of the study and the limitations of neurobehavioral workplace testing, they found evidence of neuropsychological impairment induced by exposure to acrylonitrile. However they also conclude that, given the limitations of this study, further investigations are required in order to determine if neurobehavioral toxicity is present among acrylonitrile workers in China.

Muto et al. (1992) investigated the health effects of acrylonitrile in seven Japanese acrylic fibre manufacturing factories. The study subjects were 157 male shift workers who had been exposed to for a mean of 17 years and 537 control workers with similar working conditions. The seven factories were classified into two groups according to their exposure levels in 1987, and also into three groups on the basis of 1976 exposure levels. The most highly exposed group of subjects showed a mean exposure concentration of 1.13 ppm by personal sampling. The mean exposure level for all sites was 0.53 ppm. Medical examination failed to detect any health effects attributable to long-term exposure.

Maurissen (2010) reviews the available health surveillance data relating to the neurotoxicity of acrylonitrile. It is concluded that irritation is often reported in human studies, however other reported signs or symptoms were nonspecific (headache, fatigue, weakness). It is noted that olfactory function can be reversibly affected in workers exposed to ABS products for several years, but that no convincing evidence has been provided to support neurobehavioural effects in workers exposed to AN by inhalation at ambient concentrations of 0.91 ppm or lower.

Major et al. (1998) investigated the genotoxic effects of occupational acrylonitrile and dimethylformamide (DMF) exposures over a 20-month period in the peripheral blood lymphocytes (PBL) of 26 occupationally exposed workers in a viscose rayon plant. Investigations were also performed in 26 matched control subjects, and six industrial controls (all males). Six of the 26 exposed subjects were hospitalized because of liver dysfunction that had developed due to DMF exposure. The rate of smoking was estimated on the basis of serum thiocyanate (SCN) levels. Average peak air acrylonitrile and DMF concentrations were over the maximum concentration limits at the time of both investigations.  An increase in lymphocyte count (in months 0 and 7), and severe alterations in the liver function were observed in the exposed subjects. In PBLs the proliferative rate index (PRI) was already increased in month 0 compared with the controls. Significant increases in chromosomal aberration and SCE frequencies, as well as increases in UDS were found in PBLs of the exposed subjects. The frequencies of chromatid breaks and acentric fragments further increased in month 7 and remained constantly elevated in month 20. Increased yields of both chromatid and chromosome-type exchange aberrations first appeared in month 20. The authors conclude that the cytogenetic data suggest that occupational exposures to acrylonitrile and DMF induce 'considerable genotoxic consequences' and may increase the cancer risk in the exposed human populations. The authors report a marked genotoxic effects, however the study is confounded by illness resulting from other chemical exposures. The kinds of chromosome aberrations observed (chromosome rather than chromatid type) make it uncertain whether acrylonitrile was the causative agent. The same authors (Major et al., 1999) investigated the occurrence of premature centromere division (PCD) as a possible manifestation of chromosome aberration in the peripheral blood lymphocytes of 400 Hungarian subjects. The various groups comprised 188 control donors and 212 subjects occupationally exposed to different genotoxic chemicals, such as acrylonitrile and/or dimethylformamide (DMF), benzene, cytostatic drugs, ethylene oxide (ETO), mixed exposure in the rubber industry, mixed organic solvents including CCl4, hot oil-mist, bitumen, and polychlorinated biphenyls (PCBs).  Data were compared with chromosomal aberration frequencies determined in the same samples. PCD yields were significantly higher in populations exposed to mixed chemicals, crude oil and cytostatic drugs, compared with controls. No increase in the incidence of PCDs was seen in workers exposed to acrylonitrile. With regard to human studies assessing genotoxicity endpoints, Albertini et al. (2017) concluded that, while some studies report gene and chromosome level mutations in exposed worker populations, it is important to note that it impossible to exclude confounder effects in some studies and the use of inappropriate methods in others. 

Han et al. (2008) investigated the health effects of low levels of acrylonitrile exposure on worker health. An exposed group of 267 workers was compared with a control group of 342 workers. The incidence of subjective symptoms such as headache, dizziness, palpitations, chest congestion, insomnia, sore throat and abdominal pain were significantly (p<0.01) higher in the exposed group. Anger state scores in males were also higher (p< 0.01). Blood pressure, pulse pressure, white blood cell count and ECG changes were higher in the exposed group (p<0.05). Ultrasound revealed a higher incidence of fatty liver and gall bladder cholesterol in the exposed group. Chromosomal aberration and micronuclei incidences in peripheral blood lymphocytes were significantly (p<0.01) higher in the exposed group.

Cave et al. (2011) investigated the prevalence of Cytokeratin 18 (CK18) elevation as a novel serologic biomarker of occupational liver disease in 82 ABS workers exposed to acrylonitrile, 1,3 butadiene and styrene.  CK18 was determined by ELISA and pro-inflammatory cytokines were measured by multi-analyte chemiluminescent detection.  39% of the workers had elevated CK18 levels which were not explained by alcohol or obesity, except potentially in 4 cases.  The pattern of CK18 elevation was consistent with toxicant-associated steatohepatitis (TASH) in the majority of cases (78%).  Levels of the pro-inflammatory cytokines TNFα, IL-6, IL-8, MCP-1 and PAI-1 were increased in these workers compared to those with normal CK18 levels. The authors suggest a high prevalence of occupational liver disease and TASH in elastomer/polymer workers with elevated pro-inflammatory cytokines; however it is notable that there is no correlation between the incidence of TASH and cumulative exposure to either acrylonitrile, 1,3 butadiene or styrene. Furthermore it is noted that extensive investigations of acrylonitrile in experimental animal species have not identified the liver as a primary site of toxicity at low exposure concentrations.

Zhang et al. (2012) assessed the impact of occupational exposure to low concentrations of acrylonitrile on endothelial function of the brachial artery, using colour Doppler ultrasonography. The authors conclude that long-term occupational exposure to low concentrations of acrylonitrile is harmful to endothelial function. The loss of function can be detected early by using colour Doppler ultrasonography. It is notable that the exposure concentrations of acrylonitrile are not reported and also that exposure to other chemicals and smoking are not taken into account.

 

 

 

Additional information

Health surveillance studies of occupationally exposed workers report various effects of acrylonitrile; however (with the exception of sensory irritation) studies do not report any consistent health effects of acrylonitrile; however neurobehavioural effects are noted in some studies. A review of the data concludes that there is no convincing evidence of neurobehavioural effects in workers exposed to by inhalation at concentrations of 0.91 ppm or lower. Some studies report gene and chromosome level mutations in exposed worker populations; howveer it is important to note that it impossible to exclude confounder effects in some studies and the use of inappropriate methods in others. There is therefore no convincing evidence of mutagenicity in exposed workers. A further monitoring study concludes that there is an absence of health effects attributable to long-term exposure to acrylonitrile (mean concentrations of up to 1.13 ppm) in Japanese workers.