Table 3.
Summary of skin sensitization studies of MMA.
| Species | Induction (sensitization) method | Elicitation (challenge) method | Solvent | Results | Reference |
|---|---|---|---|---|---|
| Guinea pig maximization test | |||||
| Guinea pig | Intradermal injections (day 0); occlusion (day 7) | Occlusion (day 21), open application (day 35) | Ind—80% ethanol;, peanut oil, or Aramek Elicit—Peanut oil or aramek | 2/10 3/10 | (118) |
| Guinea pig | Intradermal injections (day 0) | Ost (day 14, repeated up to 12 weeks) | Ind—Ethanol, FCA, saline Elicit—Acetone:olive oil (4:1) | 0/6 | (119) |
| Guinea pig | Intradermal injections (3 groups), occlusion (1 group) | Day 21 max nonnonirritating conc. (all groups), 24 24-h occlusion | Ind—Propylene glycol; FCA/propylene glycol; FCA; petrolatum Elicit—Non-Nonirritating conc Occlusion | 0/5 2/5 2/5 4/5 | (120) |
| Guinea pig | Intradermal injections (3 rounds, all day 0) | Day 21, 24-h occlusion | Ind—Group 1: FCA:distilled water (day 0) Group 2: MMA:saline (day 0) Group 3: MMA/saline:FCA (1:1) (day 0) All groups: 24-h occlusion (day 7) Elicit—Ethanol | 0/10 0/10 0/10 | (116) |
| Guinea pig | Occlusion (days 0, day 7) | Occlusion | Ind—(Day 0,, FCA, saline); (day 7, neat MMA) Elicit—Dilute MMA; 1% MMA: Vaseline,; 5% MMA:Vaseline (day, not described) | Negative (10% of animals treated with 1% conc.) Positive (50% of animals treated with 5% conc.) | {(121),(122) |
| Guinea pig | Intradermal injections (day 0) OST (day 7) Occlusion, 48 hour (day 8) | Occlusion (day 21) | Ind—Day 0, (FCA:Water, MMA: soybean oil, MMA:FCA:Water;) day 7, (MMA:Petrolatum, SDS); day 8, (neat MMA) Elicit—MMA 3%:petrolatum (occlusion) | 9/10 | (123) |
| Guinea pig | Intradermal injections (day 0), occlusion (day 7) | 24 hr Occlusion, 24 h (day 21) | Ind—Group 1: (Day 0, 5% MMA:Water, 10% MMA:FCA.; day 7, neat MMA.; day 24, 5% MMA) Group 2: (Day 0, 0.15% MMA:water, 0.3% MMA:FCA.; day 7, 0.15% MMA.; day 24, 100% MMA) Group 3: (Day 0, 0.001% MMA:water, 0.002% MMA:FCA.; day 7, 0.001% MMA.; day 24, 100% MMA) Group 4: (Day 0, 0.5% MMA:water, 10% MMA:FCA.; day 7, 100% MMA.; day 24, 100% MMA) Elicit—Group 1: (5% MMA occlusion, 48 h) Groups 2–4: (100% MMA, 5% MMA, acrylic particles occlusion, 48 h) | Group 1 (4/26) Group 2 (0/13) Group 3 (0/12) Group 4 (20/26) | (124) |
| Guinea pig | Intradermal injections (day 0), occlusion (day 7) | Occlusion, 24 hr (day 14) | Ind—FCA, MMA:dibutylphthalate, MMA:FCA, acetone. Elicit—Acetone | 0/10 | (125) |
| Guinea pig | Intradermal injections and topical (day 0) | Occlusion, 24 hr (day 21) | Ind—Olive oil Elicit—Acetone | 2/14 (1 M conc.) 0/10 (10–1 M conc.) 0/10 (10–2 M conc.) | (126) |
| Guinea pig | Intradermal injections Day 0: six 6 injections, six 6 sites, FCA.Day 7: SLS (24 hr)Day 8: occlusion (48 hr) | Day 21, occlusion (24 hr) | Ind—Olive oil:acetone (7:3) Elicit—neat MMA | 6/6 | (127) |
| Guinea pig | Intradermal injections, 3 control groups and 3 test groups, six 6 injections (day 0), SLS (day 6), occlusion (day 7, 48 hr) | Occlusion (days 20, Day 27; 28 hr, 48 hr, 72 hr) | Ind (test groups)—FCA:water (1:1), MMA:FCA (1%, 3%, 10% MMA) | Challenge (day 20): 1/4 (after 24, 48, 72 hr) 2/5 (after 24, 48, 72 hr) 5/5 (after 24, 48, 72 hr) Rechallenge: 1/4 (after 24, 48, 72 hr) 1/5 (after 24, 72 hr and 0/5 after 48 hr) 5/5 (after 24, 72 hr and 3/5 after 48 hr) | (128) |
| Guinea pig | Intradermal injections Day 0: six 6 injectionsDay 7: occlusion (Day 7, 48 hr) | Occlusion (day 14, 24 hr); OST (day 28) | Ind—FCA:Water (1:1), MMA 10%:maize oil, MMA 10%:FCA/water (1:1) Elicit —25% MMA; maize oil or maize oil/DMSO (day 14) then occlusion (24 hr), OST with 25 and 50% MMA in ethanol/40% DMSO (day 28). | 5/5 5/5 5/5 5/5 | (129) |
| Beuhler | |||||
| Guinea pig | Method A: OST (days 0, 2, 4, 7, 9, 11) Method B: OST (days 0, 1, 2, 3, 4, 7, 8, 9, 10, 11) | Method A: OST shaved flank (day 28, repeated up to 12 weeks)Method B: OST shaved neck (day 21, repeated up to 12 weeks) | Method A: Ethanol 95%:2-methoxyethaol: Tween 80 (9:9:2) Method B: Acetone: olive oil (1:1) | Method A: 0/6 Method B: 0/6 | (119) |
| Guinea pig | OST, 6- hour occlusion (days 0, 7, 14) | 24- hour occlusion, day 28 | Ind—neat MMA Elicit —Ethanol | 0/30 | (116) |
| Freund's complete adjuvant test (FCAT) | |||||
| Guinea pig | Intradermal injections in shoulder (days 0, 2, 4, 7, 9) | Occlusion (day 21),); OST (Day 35) | Ind—FCA Elicit—Peanut oil or Aramek (occlusion day 21); peanut oil or Aramek (day 35, OST) | 2/8 | (118) |
| Guinea pig | Intradermal injections multi-site (day 0) | Occlusion (day 14, 24 hr); OST (day 28) | Ind—1 M MMA:FCA/saline Elicit—2.5 M in maize oil (occlusion); 2.5 M in DMSO/maize oil (occlusion); 2.5 M in ethanol (OST); 5 M in ethanol (OST) | 5/55/54/55/5 | (129)* |
| Split adjuvant test | |||||
| Guinea pig | Multi-Site intradermal injections of dorsal shaved flank (day 0: FCA, day 1: MMA) | OST (day 14, repeated up to 12 weeks) | Ind—Ethanol:saline (1:100) Elicit—Acetone:olive oil (4:1) | 0/6 | (119) |
| Guinea pig | Frozen (dry Ice contact, day 0), occlusion (days 0, 3, 4, 7), intradermal injections (day 4) | Day 22, 24-h occlusion | Ind—Dry ice, ethanol, FCA:ethanol:MMA, ethanol Elicit—Ethanol | 0/30 | (116) |
| Polak | |||||
| Guinea pig | Footpad injections and intradermal injections | OST (day 7, repeated up to 12 weeks) | Ind—Ethanol:saline (1:4) Elicit—Acetone:olive oil (4:1) | 0/6 | (119) |
| Guinea pig | Footpad injections and intradermal injections (nape of neck) | Group 1: OST (day 0, reactions recorded days 2, 4, 5, 6) Group 2: OST (crossreactivity) days 7, Day 14 | Ind—Ethanol:saline (1:4) in FCA occluded, some also injected. Elicit—Acetone: olive oil (4:1) | 0/5 (8 groups) | (130) |
| Guinea pig | 6 groups: 2 hind footpad injections each group (day 0),); group 1 occlusion day 0), groups 2–3 occlusion (day 10), groups 4–5 occlusion (day 25), group 6 intradermal injection (day 25). | Groups 1–3, OST (day 35).); groups 4-6, OST (day 60) | Ind—FCA (groups 1–6) olive oil (groups 1, 3, 5); ethanol (groups 2, 4); saline injection (group 6) Elicit—Olive oil (groups 1–3, day 35); olive oil (groups 4–6, day 60) | Group 1 (0/10) Group 2 (0/5) Group 3 (0/5) Group 4 (0/5) Group 5 (0/5) Group 6 (0/5) | (131) |
| Guinea pig | Part A:6 groups: Footpad injections in each group (day 0).); OST, (all groups, days 0, 2, 5); group 4, additional intradermal injection (day 0); group 5, OST (day 25); group 6 intradermal injection (day 25).Part B:Group 4, (same as above);group 7, (footpad injection (day 0), intradermal injection (day 0) | OST (groups 1–3, day 35), OST (groups 4–6, day 60) | Ind—FCA (all groups), ethanol (groups 1–5), saline (groups 4 and 6) Elicit—Ethanol (groups 1–4), olive oil (groups 5 and 6) | Part A: Group 1 (0/25, 72 hr) Group 2 (0/24, 72 hr) Group 3 (0/25, 72 hr) Group 4 (0/10, 72 hr) Group 5 (13/13, 72 hr) Group 6 (8/8, 72 hr) Part B: Group 4 (1/10, 48 hr) Group 7 (2/10, 48 hr) | (132) |
| Draize | |||||
| Guinea pig | 10 intradermal injections over 1 week. | Intradermal injection 14 days after last induction injection (24-hour determination) | Ind—Saline Elicit—Ethanol | 2/30 | (116) |
| Mouse ear sensitization test (MEST) | |||||
| Mouse | Intradermal injection (day 0), topical application (days 0–3) | Topical application to ear (day 10) | Ind—FCA, Ethanol Elicit—Ethanol | 44% sensitized, 118% increase in ear thickness | (115) |
| Mouse | Topical application (days 0, 2) | Topical application (day 9) | Ind—Ethanol Elicit—Ethanol | 114% increase in ear thickness (24 hours after challenge, p < 0.01) | (133) |
Note. Ind = vehicle used for the “Induction (Sensitization)” procedure.;
Elicit = vehicle used for the “Elicitation (Challenge)” procedure.;
FCA = Freund's complete adjuvant;
OST = open skin testing;
SLS = sodium lauryl sulfate;
SDS = sodium dodecyl sulfate.
*
= Modified FCAT method.