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苯并[a]芘皮肤癌斜率因子的推导

Development of a dermal cancer slope factor for benzo[a]pyrene.

作者信息

Knafla A, Phillipps K A, Brecher R W, Petrovic S, Richardson M

机构信息

Equilibrium Environmental Inc., Suite 609, 815 1st Street SW Calgary, Alta., Canada T2P 1N3.

出版信息

Regul Toxicol Pharmacol. 2006 Jul;45(2):159-68. doi: 10.1016/j.yrtph.2006.02.008. Epub 2006 Apr 24.

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are commonly found at environmentally impacted sites in both Canada and the United States, and also occur naturally. Typically, benzo[a]pyrene (B[a]P) is selected as a standard to which the cancer potencies of other carcinogenic PAHs are compared. Cancer potency estimates for B[a]P have been published for the oral and inhalation routes of exposure, however, no such estimate has been established by a regulatory agency for dermal exposure. The main objectives of the current investigation were to: evaluate approaches used to examine the relative carcinogenicity of PAHs; to conduct a review of mammalian dermal carcinogenicity studies for B[a]P; and derive a cancer slope factor for dermal exposure to PAHs using B[a]P as a surrogate for other PAHs. The toxicological database of dermal B[a]P studies was examined for relevant animal bioassays. Seven relevant studies were identified. A cancer slope factor for B[a]P was developed using the benchmark dose approach and the linearized multistage model. The upper 95th CI at the 5% effect level above background incidence was used as the point of departure for low-dose linear extrapolation. An average slope factor of 0.55 (microg/animal day)(-1) was calculated for mice, which was converted to a dose-equivalent slope factor of 25 (mg/kg day)(-1). This latter slope factor is proposed for application to human health risk assessment with no scaling adjustment. Dermal potency equivalency factor values were identified which may be used with other carcinogenic PAH in the calculation of total B[a]P equivalent dermal cancer risk estimates. An identified area for further investigation is the consideration of scaling in extrapolating the calculated dermal cancer slope factor from mice to humans.

摘要

多环芳烃(PAHs)在加拿大和美国受环境影响的地区普遍存在,并且也天然存在。通常,苯并[a]芘(B[a]P)被选作一种标准,其他致癌性多环芳烃的致癌效力会与之进行比较。关于B[a]P经口和吸入暴露途径的致癌效力估计值已经公布,然而,监管机构尚未确定经皮肤暴露的此类估计值。本次调查的主要目的是:评估用于检验多环芳烃相对致癌性的方法;对B[a]P的哺乳动物皮肤致癌性研究进行综述;并以B[a]P作为其他多环芳烃的替代物,推导经皮肤暴露于多环芳烃的癌症斜率因子。对皮肤B[a]P研究的毒理学数据库进行了相关动物生物测定的审查。确定了七项相关研究。使用基准剂量法和线性化多阶段模型制定了B[a]P的癌症斜率因子。将高于背景发病率5%效应水平时的第95百分位上限置信区间用作低剂量线性外推的出发点。计算得出小鼠的平均斜率因子为0.55(微克/动物·天)⁻¹,将其转换为剂量当量斜率因子为25(毫克/千克·天)⁻¹。建议将后一个斜率因子应用于人类健康风险评估,且无需进行比例调整。确定了皮肤效力等效因子值,可在计算总B[a]P等效皮肤癌风险估计值时与其他致癌性多环芳烃一起使用。一个有待进一步研究的领域是在将计算得出的皮肤癌斜率因子从小鼠外推至人类时考虑比例缩放。

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