Thus, taken together, the data available indicate that styrene does not have the potential to impair fertility and reproductive … Overall, there were no statistically significant maternal effects on body weight at 0.64mg/L. Hind limb grip strength was decreased (18%) at day 45, but only in 500 ppm exposed males, and without any effects on days 22 and 60. While it is difficult to reconcile the exposure conditions experienced by experimental animals in a 2-generation reproductive study with exposures of pregnant women in the workplace, the maternal and paternal exposure patterns for the F1 generation (i.e. Photoinitiator Free Resins Composed of Plant-Derived Monomers for the Optical µ-3D Printing of Thermosets. Chamkhia et al., (2006) treated male rats (2-3 months of age) over ten days with 600 mg/kg bw/d by the intraperitoneal route. Therefore, there is no convincing evidence that styrene has shown genotoxic activity in humans. -         F2 pups: body weights were significantly reduced during pre-weaning in males at 150 and 500 ppm and in females at 500 ppm. In this respect it should be taken into consideration that in total more than 140 different observations are statistically analyzed. PMID: 3722710 [PubMed - indexed for MEDLINE]  |  Numerically and statistically significant reductions in body weight were also measured in F0 and F1 male rats respectively in the 150 ppm treatment group. There were statistically significant reductions in bodyweights at pnd 13 and 21 in male F2 offspring of F1 rats exposed to 150 ppm. there were no effects up to 500 ppm in F1 pups during pre-weaning, (a true developmental effect would become evident especially in this early phase). First of all, the following general considerations must be taken into consideration: Point of life span and generation affected: All the effects taken by RAC were only observed in the second generation. Therefore, in summary the weight of evidence does not give an indication for adverse effects of styrene on male reproductive parameters. Luderer et al. The magnitude of the effect on day 60 was larger than the effect on body weight, potentially indicating a neuromuscular effect. Studies of general population environmental and consumer exposure and cancer are less informative than the occupational cohort studies given generally lower number of subjects and imprecise exposure information. The reason is linked to the fact that styrene exposures in the F0 generation began when the rats were fully mature, corresponding to the time when humans will enter the workforce. Based on these exposure considerations the developmental toxicity results for the offspring of the F0 generation, (i.e. In rats and mice, styrene exposures can produce toxicity to the olfactory epithelium of the nasal cavity. This may be taken as not being a general response to maternal toxicity as no statistically significant effects on bodyweights of F1 females at 150 ppm were observed during premating and gestation. Considering the nature of the workplace exposures and the physiology of prolactin, work-place stress has been identified as a plausible explanation for the observed prolactin elevations. It is not possible to assign the effects reported to any specific substance, In the rat, inhalation exposure produced no evidence of significant effects on conventional parameters assessed in the foetus at non-maternally toxic exposure concentrations of up to 600 ppm styrene (Murray et al., 1978). The RAC notes that in both studies there are observations of effects on time of eye opening, righting reflex, and incisor eruption, and that these effects fit the pattern of effects observed in the two-generation study. Although the clinical relevance of these findings is unclear, the findings warrant further investigation. There was a dose related decrease of sperm counts and motility and an increase of the percentage of abnormal sperm. Cat 3; R63, is warranted according to the DSD.“. The expression of clusterin mRNA was decreased in a dose related manner in testes (but not in other organs) while some other mRNAs were upregulated. Styrene exposure impaired rat operant behaviour at 500 and 1000 ppm, but not at 50 or 150 ppm. The high variability of pituitary weights in conjunction with the very low absolute weights (between 0.6 and 10.9 mg for F2 pups) may lead to misinterpretations caused by chance variation. 2 classification were as follows (taken from RAC (2012) verbally): “The RAC notes the dose-dependent decrease in pup weights in the second generation offspring (F2), and although there were some effects on the F1 maternal body weight at the top dose (reduction by 7-8%), the reduced growth of the pups at the mid dose supports that this could be a direct effect on the offspring. Styrene-induced mouse lung tumors are likely not relevant to humans. The historical data of the laboratoryfrom 20 studies show the swin time for the F2 pups from the 500 ppm group are within the historical control values while the swim time of the concurrent controls is particularly fast: The table shows that there are statistically significant decreases in male bodyweights also periodically in the F0 and F1 parental generations exposed to 150 ppm. 2005 Jun;74(3):221-32. doi: 10.1002/bdrb.20042. Res Rep Health Eff Inst. Close Find out more on how we use cookies. (2005b) were assessed in detail in the RAC opinion leading to the conclusion to classify styrene as a category 2 developmental toxicant: - a decreased pup growth in F2 offspring at 150 and 500 ppm (7-10% and 10-13%, respectively). (2015) reviewed the literature on potential endocrine effects of styrene for (anti)estrogenicity, (anti)androgenicity, interruption with thyroidal regulation and effects on prolactin serum levels. 38.4 g), again showing variability in data. (1999) will not be considered here because the toxicological relevance can hardly be assessed without a clear association to other guideline parameters. Only studies in the rat are available using the oral route of exposure; generally no significant effects on any of the conventional parameters assessed in the foetus were seen at dose levels up to 250 mg/kg/day, at which maternal toxicity was observed (Murray et al., 1976; Srivastava et al., 1990). From the other relevant studies available, there is no convincing evidence that styrene can impair reproductive performance, produce testicular toxicity, sperm abnormalities or adversely affect the reproductive organs (Cruzan et al., 1997; 1998; 2001; NCI 1979; Quast 1979). However, this slight shift was considered to be related to the growth delay evident in this group of animals particularly in the pre-weaning stage. However, in the two-generation study, F2 pup body weights were reduced already on day 0 (“, Piersma, A. H. et al., Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: On the impact of parameters related to F1 mating and F2 offspring.