For example Moser (1991) introduced the concept of functional domains which involves grouping inter-correlated endpoints to examine patterns of response (Moser V. Applications of a Neurobehavioral Screening Battery. During post-weaning, (when rats where exposed to styrene), significant reductions in body weights were noted in both male and female rats in the 500 ppm exposure group and in male animals in the 150 ppm exposure group. The delay in attaining some pre-weaning developmental landmarks (pinnal detachment, surface righting response, incisor eruption and hair growth) and in acquiring preputial separation, the decreased straight channel swimming ability, the slight shift in the normal pattern of motor activity and the reduction in forelimb grip strength observed in this study are parameters known/likely to be body weight-sensitive and hence are not considered to represent a direct and specific expression of styrene developmental neurotoxicity, but the consequence of generalised toxicity. -        There are also clear reductions in bodyweights in both the F1 and F0 females exposed to 150 ppm but without reaching statistical significance, including the F1 maternal animals during gestation, -        While the bodyweights of F2 offspring males at 150 ppm were significantly different from F2 control body weights (i.e. These results indicate that inhalation exposures at these concentrations produce reproductive and development toxicity, as well as maternal toxicity. Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents. The rats of the 0 and 100 ppm groups were then mated and exposed to 0 or 100 ppm styrene oxide daily through 18 days of gestation (dg). Reproductive toxicology of inhaled styrene oxide in rats and rabbits. Investigated as a tumorigen, mutagen, reproductive effector. 1B, H360 (CLP) is not appropriate. A well-conducted two-generation inhalation study (Cruzan et al., 2005a) found no effects on fertility and reproductive performance in rats exposed to up to 500 ppm (2165 mg/m3, ca.300 mg/kg/day) styrene, a concentration causing parental toxicity (degeneration of the olfactory epithelium and reductions in body weights). 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). It may be argued that the reduction in bodyweight (10-13%) in the F2 pups is insufficient to explain the increase in swim time on pnd 24 (30-40%), -        males: 10.6 seconds (500 ppm) versus 7.5 seconds (0 ppm), -        females: 11.4 seconds (500 ppm) versus 7.8 seconds (0 ppm). This evaluation was based on negative in vitro studies for estrogenic activity (Nobuhara et al., 1999; Ohno et al., 2001) and androgenic activity (Nobuhara et al., 1999) and on a negative uterotrophic assay in female rats (Nobuhara et al., 1999). NIH There are many studies that have examined the genotoxic potential of styrene in styrene exposed workers. 500 ppm. The nervous system is the most sensitive target of long-term styrene exposure. There are no indications that occupational or environmental exposures to styrene produces adverse effects on fertility or development including potential endocrine disruptor effects. The 500 ppm level produced maternal toxicity. A significant increase in fore-limb grip strength in females at PND 45 in the 150 ppm group indicated to variability of the effect. NTP CERHR MON. (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). Developmental effects after inhalation exposure of gravid rabbits and rats to ethylene glycol monoethyl ether. There were no statistically significant effects on body weights in the mid-exposure females of the F0 and F1 generations, although reductions of up to 5-6% were observed in the F1 females during the study including gestation. The non-specific delay in development characterized by reduced weight gain seen in the two-generation reproduction study was accompanied by a slight delay in acquisition of few individual parameters used to investigate motor activity which were measured as part of a developmental neurotoxicity investigation linked to the 2-generation reproductive study – see below. An important question relating to the above data is whether the small reductions in body weights reflect a specific developmental effect or simply a general low level toxicological or behavioral consequence of high exposures to styrene. 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). Studies of general population environmental and consumer styrene exposure and cancer are less informative than the worker studies, but the available evidence does not suggest these low exposures are a concern. Willkommen auf der Website der ECHA! 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. At exposures in excess of 50 ppm (8-hour time-weighted average), styrene may cause temporary nervous system effects such as drowsiness and delayed reaction time. Ad 2: reduced forelimb grip strength on pnd 60 at 500 ppm: It is well known that body weight and grip strength are correlated (Maurissen et al., 2003). The human cancer evidence for styrene and workplace exposure is inconclusive and not supported by animal toxicity and mechanistic information but, as such, remains a concern. The correlation between body weight and preputial separation in rats is clearly established. J. On the other hand, if it is the developmental rate of the pituitary that is affected, the lack of pathological findings may be consistent with the decreased weight. The table shows the days of acquisition of the developmental landmarks and only for incisor eruption statistical significance (*p<0.05) is obtained, On pnd 0-21 the mean F2 pup weights at 500 ppm were statistically lower (7-13%) than those of the 0 ppm control animals as shown in the following table (* p<0.05). Styrene oxide, like many intermediate metabolites of foodstuffs, is genotoxic and, if introduced directly into the stomachs of rodents in high doses/concentrations, gives rise to cancers of the forestomach. males: 10.6 seconds (500 ppm) versus 7.5 seconds (0 ppm), females: 11.4 seconds (500 ppm) versus 7.8 seconds (0 ppm). Coccini et al. 202-787-5996. 400 E Joppa Road, Suite 108 A 2009 study of German boat-building workers found no significant associations between color vision and styrene exposures up to 50-100 ppm. COVID-19 is an emerging, rapidly evolving situation. However, no difference was seen at PND 62. It is noted that, in contrast to previous investigations, in this OECD- and GLP-compliant study the delay in pup development was seen at an exposure level causing some maternal toxicity (reductions in body weights of 6-7% and degeneration of the nasal olfactory epithelium). Clipboard, Search History, and several other advanced features are temporarily unavailable.  |  Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice. No information is available for the selection of the 60 workers out of a total of 1000 and about participation rate. Although some study authors have concluded that styrene is either a human or an animal reproductive or developmental toxicant, careful review demonstrates that such conclusions are not justified. Developmental or reproductive toxicity studies have been conducted in rats, mice, rabbits, and hamsters. There is suggestive evidence that exposure to styrene in occupational settings is associated with increased serum prolactin and depletion of peripheral blood dopamine metabolizing enzyme activities relative to unexposed individuals. These effects were statistically significant at the highest dose level. 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. Therefore, in summary the weight of evidence does not give an indication for adverse effects of styrene on male reproductive parameters. if maternity leave not taken), it is most unlikely that inhalation exposures to styrene will occur in humans directly after post-weaning through to beginning of maturity which is the exposure regimen experienced by the F1 generation producing the F2 pups. 1994;24 Suppl:S49-55. The rats were killed at 20 dg and the rabbits at 30 dg. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). But numerical data and a statistical analysis are missing. The four endpoints taken by RAC for their classification decision require that much more details must be taken into consideration to come to a well-founded decision: There were numerical reductions in body weights in F1 and F0 dams already at 150 ppm during premating and gestation although not reaching statistical significance.