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Role of xenoestrogens on the occurrence of premenopausal breast cancer in Iran
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Abstracts / Toxicology Letters 211S (2012) S43–S216
related adverse effects. On the other hand, in a social setting animals experience birth events and handling of neonates by watching cage mates, and neonates/infants have cage mates of comparable ages to interact with. Qualitative assessment in several hundred pregnant NHPs under social housing indicates good compatibility with little aggression towards each other. Conceivably the delivery process and managing the newborn is facilitated by social maternal housing. Compared to single-housing, a 5–10% reduction of preand postnatal loss parameters was encountered under social housing, and stillbirth rate dropped by approx. 50%. In conclusion, social housing is feasible for developmental toxicity studies in NHPs and is meanwhile the default in our laboratory. doi:10.1016/j.toxlet.2012.03.675
P30-21 A developmental toxicity evaluation comparing Lister Hooded with Wistar Han rats Raluca Kubaszky, David Esdaile, Balasz Komuves
This study aimed to focus on tissue levels of AhR and its association with exposure to chemicals with estrogen-like activities in premenopausal breast cancer. Fifty premenopausal women were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories that generate PAHs and dioxins was considered as the major risk factor in premenopausal breast cancer (p = 0.001, OR = 4.8). History of idiopathic infertility was identified as the second significant risk factor (p = 0.002, OR = 3.50), which could be affected by endogenous estrogen levels. Long term (>5 years) consumption of oral contraceptive pills was identified as the third most important risk factor (p = 0.006, OR = 2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p = 0.005, OR = 1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors. doi:10.1016/j.toxlet.2012.03.677
CiToxLAB, Hungary In regulatory developmental toxicity studies the Wistar Han outbred rat is commonly used. To meet specific study objectives other strains may be used, for example if a non-albino strain is required. The purpose of this work was to make a comparative assessment of control data from Lister Hooded HsdOla:LH (LH) and Wistar Han HsdHan:WIST (WH) rats, based on data from four standard ICH studies performed under GLP and AAALAC animal welfare standards. LH and WH rats were obtained from Harlan Laboratories Europe and mated following oestrus cycle examination, at ∼11 weeks of age. Caesarean sections were conducted on gestation day GD20 and foetuses examined for external, visceral and/or skeletal examination. Comparisons were made between 38 LH litters with 439 foetuses and 52 WH litters with 548 foetuses on both total foetuses and on a per litter basis. The mean terminal corrected body weights of the dams were similar (LH 8% below WH), but the foetal weights were significantly different (LH 30% below WH) with a slightly higher mean litter size (LH at 11.6 and WH at 10.6). The incidences of foetal abnormalities were similar (External: LH at 3.6% and WH at 3.3%. Visceral: LH at 5.4% and WH at 3.3%. Skeletal: LH at 16% and WH at 14%). The range and types of background variations between the strains were generally similar. In conclusion, comparative data were found to be useful in study interpretation and Lister Hooded rats were considered to be a suitable pigmented strain for use in developmental toxicology studies. doi:10.1016/j.toxlet.2012.03.676
P30-22 Role of xenoestrogens on the occurrence of premenopausal breast cancer in Iran Sepideh Arbabi Bidgoli Islamic Azad University (IAUPS), Iran Breast cancer affects Iranian women at least one decade younger than their counterparts in other countries but the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities which may compromise ovarian functions of women in polluted environments.
P30-23 Maximum possible human boron exposures are insufficient to cause reproductive effects R. Wayne Ball Rio Tinto Minerals, United States Comparison of the absorbed dose of boron (B) demonstrates that human exposures are significantly lower than those in animal studies. Background B levels in standard rat chow are high (10 ppm), as a result control rats in toxicity studies receive 45× more B than background exposure in humans. Blood B levels in control rats is about 0.23 g B/g, approximately equal to the blood levels in boron industry workers in China, Turkey and U.S. of 0.25, 0.22 and 0.26 g B/g, respectively. Workers in the B mining and processing industries would logically represent the maximum levels of human exposure, but their blood B levels are about the same as un-treated control animal exposures. This provides an explanation why studies of highly exposed B industry workers have shown no adverse effects. No adverse effects on sperm were seen in Turkish B industry workers or in the most highly exposed subgroup of Chinese B industry workers drinking B-contaminated water (mean blood level 1.52 g B/g, the human NOAEL). The blood level at the lowest animal LOAEL (13 mg B/kg) was 1.53 g B/g, about 6× greater than typical B industry workers. Only under extreme conditions do human levels reach those of this animal LOAEL: the subgroup of Chinese boron workers who also drank contaminated water. These demonstrate that maximal human exposures are not sufficient to cause reproductive toxicity effects and do not support the classification in Europe of boric acid as Category 1(B) reproductive toxicant, which is based on laboratory animal studies. doi:10.1016/j.toxlet.2012.03.678
Abstracts / Toxicology Letters 211S (2012) S43–S216
related adverse effects. On the other hand, in a social setting animals experience birth events and handling of neonates by watching cage mates, and neonates/infants have cage mates of comparable ages to interact with. Qualitative assessment in several hundred pregnant NHPs under social housing indicates good compatibility with little aggression towards each other. Conceivably the delivery process and managing the newborn is facilitated by social maternal housing. Compared to single-housing, a 5–10% reduction of preand postnatal loss parameters was encountered under social housing, and stillbirth rate dropped by approx. 50%. In conclusion, social housing is feasible for developmental toxicity studies in NHPs and is meanwhile the default in our laboratory. doi:10.1016/j.toxlet.2012.03.675
P30-21 A developmental toxicity evaluation comparing Lister Hooded with Wistar Han rats Raluca Kubaszky, David Esdaile, Balasz Komuves
This study aimed to focus on tissue levels of AhR and its association with exposure to chemicals with estrogen-like activities in premenopausal breast cancer. Fifty premenopausal women were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories that generate PAHs and dioxins was considered as the major risk factor in premenopausal breast cancer (p = 0.001, OR = 4.8). History of idiopathic infertility was identified as the second significant risk factor (p = 0.002, OR = 3.50), which could be affected by endogenous estrogen levels. Long term (>5 years) consumption of oral contraceptive pills was identified as the third most important risk factor (p = 0.006, OR = 2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p = 0.005, OR = 1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors. doi:10.1016/j.toxlet.2012.03.677
CiToxLAB, Hungary In regulatory developmental toxicity studies the Wistar Han outbred rat is commonly used. To meet specific study objectives other strains may be used, for example if a non-albino strain is required. The purpose of this work was to make a comparative assessment of control data from Lister Hooded HsdOla:LH (LH) and Wistar Han HsdHan:WIST (WH) rats, based on data from four standard ICH studies performed under GLP and AAALAC animal welfare standards. LH and WH rats were obtained from Harlan Laboratories Europe and mated following oestrus cycle examination, at ∼11 weeks of age. Caesarean sections were conducted on gestation day GD20 and foetuses examined for external, visceral and/or skeletal examination. Comparisons were made between 38 LH litters with 439 foetuses and 52 WH litters with 548 foetuses on both total foetuses and on a per litter basis. The mean terminal corrected body weights of the dams were similar (LH 8% below WH), but the foetal weights were significantly different (LH 30% below WH) with a slightly higher mean litter size (LH at 11.6 and WH at 10.6). The incidences of foetal abnormalities were similar (External: LH at 3.6% and WH at 3.3%. Visceral: LH at 5.4% and WH at 3.3%. Skeletal: LH at 16% and WH at 14%). The range and types of background variations between the strains were generally similar. In conclusion, comparative data were found to be useful in study interpretation and Lister Hooded rats were considered to be a suitable pigmented strain for use in developmental toxicology studies. doi:10.1016/j.toxlet.2012.03.676
P30-22 Role of xenoestrogens on the occurrence of premenopausal breast cancer in Iran Sepideh Arbabi Bidgoli Islamic Azad University (IAUPS), Iran Breast cancer affects Iranian women at least one decade younger than their counterparts in other countries but the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities which may compromise ovarian functions of women in polluted environments.
P30-23 Maximum possible human boron exposures are insufficient to cause reproductive effects R. Wayne Ball Rio Tinto Minerals, United States Comparison of the absorbed dose of boron (B) demonstrates that human exposures are significantly lower than those in animal studies. Background B levels in standard rat chow are high (10 ppm), as a result control rats in toxicity studies receive 45× more B than background exposure in humans. Blood B levels in control rats is about 0.23 g B/g, approximately equal to the blood levels in boron industry workers in China, Turkey and U.S. of 0.25, 0.22 and 0.26 g B/g, respectively. Workers in the B mining and processing industries would logically represent the maximum levels of human exposure, but their blood B levels are about the same as un-treated control animal exposures. This provides an explanation why studies of highly exposed B industry workers have shown no adverse effects. No adverse effects on sperm were seen in Turkish B industry workers or in the most highly exposed subgroup of Chinese B industry workers drinking B-contaminated water (mean blood level 1.52 g B/g, the human NOAEL). The blood level at the lowest animal LOAEL (13 mg B/kg) was 1.53 g B/g, about 6× greater than typical B industry workers. Only under extreme conditions do human levels reach those of this animal LOAEL: the subgroup of Chinese boron workers who also drank contaminated water. These demonstrate that maximal human exposures are not sufficient to cause reproductive toxicity effects and do not support the classification in Europe of boric acid as Category 1(B) reproductive toxicant, which is based on laboratory animal studies. doi:10.1016/j.toxlet.2012.03.678