Loewengart G, Van Duuren B L
J Toxicol Environ Health. 1977 Jan;2(3):539-46. doi: 10.1080/15287397709529454.
Tetrakis(hydroxymethyl)phosphonium chloride (THPC) and Pyroset TKP, which is the mixed acetate/phosphate of the same phosphonium base, are widely used in flame-retardant cotton fabrics, particularly in children's sleepwear. THPC degrades thermally and under certain chemical conditions to yield hydrochloric acid and formaldehyde (CH2O). In solution, the latter two compounds are in equilibrium with the known potent carcinogen bis(chloromethyl)ether (BCME). A sample of commercial THPC contained from 4% (at pH 0.4) to 14% (at pH greater than 4.5) free CH2O. The material, as supplied by the manufacter, showed pH 0.4. Gas chromatographic analysis of aqueous commercial THPC did not reveal any peak chracteristic of BCME under conditions where 0.1 ppm of the material can be detected. Application to mouse skin of THPC ( 2 mg in 0.1 ml DMSO) and of Pryset TKP (7 mg in 0.1 ml DMSO), three times per week for 400 days with 20 female ICR/Ha Swiss mice per group, gave one squamous carcinoma in the THPC-treated group. THPC was inactive as an initiating agent in two-stage mouse skin carcinogenesis with phorbol myristate acetate as promoter. Both agents were active as tumor promoters, using a single application of 7,12-dimethylbenz[a]anthracene (20 microng in 0.1 ml acetone) as initiator. With THPC as promoter (2 mg in 0.1 ml DMSO, thrice weekly) 3 of 20 mice bore papillomas which progressed to squamous carcinoma. With Pyroset TKP as promoter (7 mg in 0.1 ml DMSO) 7 of 20 mice bore papillomas of which two progressed to squamous carcinoma.
四羟甲基氯化鏻（THPC）和Pyroset TKP（即同一鏻碱的乙酸盐/磷酸盐混合物）被广泛用于阻燃棉织物，尤其是儿童睡衣。THPC在热和某些化学条件下会降解，产生盐酸和甲醛（CH₂O）。在溶液中，后两种化合物与已知的强致癌物双（氯甲基）醚（BCME）处于平衡状态。一份市售THPC样品中游离CH₂O的含量为4%（pH值为0.4时）至14%（pH值大于4.5时）。制造商提供的该材料pH值为0.4。在能够检测到0.1 ppm该物质的条件下，对市售THPC水溶液进行气相色谱分析未发现任何BCME的特征峰。将THPC（0.1 ml二甲基亚砜中含2 mg）和Pyroset TKP（0.1 ml二甲基亚砜中含7 mg）涂抹于小鼠皮肤，每组20只雌性ICR/Ha瑞士小鼠，每周3次，持续400天，结果在THPC处理组中有1只小鼠发生了鳞状细胞癌。在以十四酰佛波醇乙酸酯为促癌剂的小鼠皮肤两阶段致癌过程中，THPC作为引发剂没有活性。以单次涂抹7,12 - 二甲基苯并[a]蒽（0.1 ml丙酮中含20微克）作为引发剂时，这两种物质作为促癌剂均有活性。以THPC作为促癌剂（0.1 ml二甲基亚砜中含2 mg，每周三次）时，20只小鼠中有3只长出了乳头状瘤，并进展为鳞状细胞癌。以Pyroset TKP作为促癌剂（0.1 ml二甲基亚砜中含7 mg）时，20只小鼠中有7只长出了乳头状瘤，其中2只进展为鳞状细胞癌。
