title: Evaluation of irritancy and sensitization potential of metalworking fluid mixtures and components.
abstract: There are approximately 1.2 million workers exposed to metalworking fluids (MWF), which are used to reduce the heat and friction associated with industrial machining and grinding operations. Irritancy and sensitization potential of 9 National Toxicology Program (NTP) nominated MWFs (TRIM 229, TRIM VX, TRIM SC210, CIMTECH 310, CIMPERIAL 1070, CIMSTAR 3800, SYNTILO 1023, SUPEREDGE 6768, and CLEAREDGE 6584) were examined in a combined local lymph node assay (LLNA). BALB/c mice were dermally exposed to each MWF at concentrations up to 50%. Significant irritation was observed after dermal exposure to all MWFs except CIMTECH 310 and SYNTILO 1023. Of the 9 MWFs, 6 induced greater than a 3-fold increase in lymphocyte proliferation and 7 tested positive in the irritancy assay. TRIM VX yielded the lowest EC3 value (6.9%) with respect to lymphocyte proliferation. Chemical components of TRIM VX identified using HPLC were screened for sensitization potential using structural activity relationship (SAR) modeling and the LLNA. TOPKAT predicted triethanolamine (TEA) as a sensitizer while Derek for Windows predicted only 4-chloro-3-methylphenol (CMP) to be positive for sensitization. When tested in the LLNA only CMP (EC3 = 11.6%) and oleic acid (OA) (EC3 = 29.7%) were identified as sensitizers. Exposure to all tested TRIM VX components resulted in statistically significant irritation. An additive proliferative response was observed when mixtures of the two identified sensitizing TRIM VX components, OA and CMP, were tested in the LLNA. This is one explanation of why the EC3 value of TRIM VX, with respect to lymphocyte proliferation, is lower than those assigned to its sensitizing components.
authors.affiliation: National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. sanderson4@cdc.gov
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Anderson
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Brown
authors.forename: Leon F
authors.initials: LF
authors.lastname: Butterworth
authors.forename: Adam
authors.initials: A
authors.lastname: Fedorowicz
authors.forename: Laurel G
authors.initials: LG
authors.lastname: Jackson
authors.forename: H Fred
authors.initials: HF
authors.lastname: Frasch
authors.forename: Don
authors.initials: D
authors.lastname: Beezhold
authors.forename: Albert E
authors.initials: AE
authors.lastname: Munson
authors.forename: B J
authors.initials: BJ
authors.lastname: Meade
mesh_terms: D000485:Allergens / Q000276:immunology / Q000633:toxicity; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002733:Chlorophenols / Q000276:immunology / Q000494:pharmacology; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology*; D054644:Ear Auricle / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D007509:Irritants / Q000276:immunology / Q000633:toxicity*; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008669:Metallurgy; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology; D016273:Occupational Exposure / Q000009:adverse effects; D019301:Oleic Acid / Q000276:immunology / Q000494:pharmacology; D009930:Organic Chemicals / Q000276:immunology* / Q000633:toxicity*; D023422:Skin Irritancy Tests; D013329:Structure-Activity Relationship
chemical_list: C515248:3-methyl-4-chlorophenol; D000485:Allergens; D002733:Chlorophenols; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D004983:Ethanolamines; D007509:Irritants; D039821:Monoterpenes; D009930:Organic Chemicals; C016775:alpha-terpineol; D019301:Oleic Acid; C009546:triethanolamine