Rat Wistar HsdCpb:Wu 9–13 wk 171–189 g F Oral Gavage 2000 mg/kg bw Test material purity: 99.3% methiocarb Observation period: min 14 d PEG 400 Results: There were no mortalities, clinical signs or gross pathological findings. Conclusion: The acute oral LD50 of methiocarb-sulfoxide-phenol is > 5000 mg/kg bw Gillisen, U. (2007b) 29-Aug-2007 Study ID: T 5077 975 Report-No: AT04054 Document No.: M-292384-01-1) sulfoxide-phenol
Observation period: 72 h Conclusion: Methiocarb is not a skin irritant. Eye irritation Species Strain, age weight Sex Route Test parameters (e.g. dose) Vehicle Toxicology conclusion/s Reference information Rabbit NZ White Young adult 14–16 wk 3.107–3.398 kg M & F Ocular (conjunctival sac of the left eye). 0.1 g dose of test item (undiluted) Test material: methiocarb (purity: 98.2%) n = 3 (2F, 1M) Exposure Time: ~1 h (then eye-rinse) Observation period: 72 h Nil Results: The test item applied in the eye of the rabbits caused slight changes on the conjunctivae: hyperaemia grade 1, at the time point in 3/3 test eyes. All irritation signs had returned to normal by the 24-h time point following treatment. Additional ocular effect noted was miosis (contraction of the pupil) at the 1-h time point in 1/3 animals. There were no other behavioural and clinical alterations observed. Conclusion: Methiocarb is not an eye irritant. Collor, L.V.M. (2005b) 27-Sept-2005 (Report-No: RF - 0030.312.405.05 Document No.: M-261818-01-1)
Skin sensitisation Species Strain, age weight Sex Route Test parameters (e.g. dose) Vehicle Toxicology conclusion/s Reference information Guinea Pig (Cavia porcellus) Hartley 9 wk 403-520 g M Epidermal 0.5 g dose of test item (undiluted) Test material; methiocarb (purity 98.2%). 7 d gap between inductions (3), & then 14 d to challenge (total: 29 d) n = 10 Exposure Area = 6 cm2 Exposure Time = 6 h Observation period: 30 d Buehler’s closed patch technique (absorbent cotton lint) Results: No skin reactions were observed. Also no clinical signs nor behavioural alterations were observed. Conclusion: Methiocarb is not a skin sensitiser. Ferreira, T.G. 11-July-2013 (Study/Report-No: RF - 0030.318.279.05 Document No.: M-261825-02-1) Genotoxicity Species Strains Test parameters (e.g. dose) Vehicle Toxicology conclusion/s Reference information Salmonellla typhimurium (LT2 mutants) TA 1535, TA 100, TA 1537, TA98, and TA 102. Plate incorporation test: 16–5000 µg test material per plate Test material purity: 99.1% methiocarb phenol Nutrient broth (usually Oxoid No. 2) Conclusion: Methiocarb-phenol was considered to be non-mutagenic without and with S9 mix. Herbold, B. (2007a) 24-Sept-2007 (Study ID: T 9077 762 Report-No: AT04108 Document No.: M-292915-01-1)
Salmonellla typhimurium (LT2 mutants) TA 1535, TA 100, TA 1537, TA98, and TA 102. Plate incorporation test: 16–5000 µg test material per plate Test material purity: 99.3% methiocarb sulfoxide phenol Nutrient broth (usually Oxoid No. 2) Conclusion: Methiocarb-sulfoxide-phenol is considered to be non-mutagenic without and with S9 mix. Herbold, B. (2007b) 28-Sept-2007 (Study ID: T 4077 767 Report-No: AT04135 Document No.: M-293116-01-1) Salmonellla typhimurium (LT2 mutants) TA 1535, TA 100, TA 1537, TA 98, and TA 102. Plate incorporation test: 16–5000 µg test material per plate Test material purity: 99.4% methiocarb sulfone phenol Nutrient broth (Oxoid No. 2) Conclusion: Methiocarb-sulfone-phenol is considered to be non-mutagenic without and with S9 mix. Herbold, B. (2007c) 22-Nov-2007 (Study ID: T 3077 766 Report-No: ATO 4261 Document No.: M-294754-01-1) Salmonellla typhimurium (LT2 mutants) A 1535, TA 100, TA 1537, TA98, and TA 102. Plate Incorporation test: 0–5000 µg test material per plate Test material purity: 98.2% methiocarb Nutrient broth Conclusion: Methiocarb technical is considered to be non-mutagenic (as measured in this Salmonella typhimurium reverse mutation assay), at concentrations of ≤ 333 µg. Henninger, K. 17-June-2015 (Study ID: 1690 601 [Harlan] Document No.: M-524333-01-1)
Sub-chronic toxicity Species Strain, age, weight Sex Route Test parameters (e.g. dose) Vehicle Toxicology conclusion/s Reference information Dog Beagle Age: Not >6 m Mean bw (g) : M : 9153.5–9437.5 F: 7081.8–8177.0 M & F Diet Test material: > 99% purity methiocarb 0, 10, 50 or 250 ppm (equal to 0, 0.3, 1.3 or 5.9 mg/kg bw/d in males and 0, 0.25, 1.3 or 6.5 mg/kg bw/d in females) n = 4/sex/treatment Exposure time: 90 day Observation period: 90 days - Conclusions: NOAEL for plasma cholinesterase = 10 ppm (0.30 and 0.25 mg/kg bw/d in males and females respectively). Jones, R.D. & Stuart, B.P. 7-Dec-2000 (Study No.: 99-S76-BG Report-No: 109807 Document No.: BC9387 / MO-00-016374 Record No.: M-064316-01-1) Rat SPF-bred Wistar strain Hsd Cpb:WU 5-6 wk Mean initial body weights: M 136–139 g F 132–137 g M & F Diet Test material: 98.9% purity methiocarb 0, 100, 300 or 900 ppm (equal to 0, 7.3, 22.7 or 67.6 mg/kg bw/d in males and 0, 10.0, 30.7 or 90.7 mg/kg bw/d in females respectively) Note: a separate, concurrent used 0 ppm & 900 ppm treatments only. n = 10/sex/group - Conclusions: Based on reduced relative body weight. NOAEL = 22.7 and 30.7 mg/kg bw/d in males and females respectively. Kroetlinger, F 11-Dec-2001 (Study No.: T 9069 842 Report-No: PH 31598 Document No.: 31598 / MO-01-021994 Record No.: MO-01-021994 / M-088469-01-1)
M: 115 g F: 101 g & F2 generations 50 ppm: M 4.3 4.2 F 5.5 6.0 150 ppm: M 12.5 13.5 F 15.4 18.6 500 ppm: M 41.0 43.5 F 52.1 61.3 n = 25 animals/sex/dose/generation [LOAEL = 150 ppm: decreased body weight] NOAEL offspring toxicity = 50 ppm: M = 4.3 & F = 5.5 [LOAEL = 150 ppm: decreased lactation index] Record No.: MO-02-002596 / M-036790-01-1) Rat Wistar CrIGIxBrlHan: Wl F0 animals: 5–6 wk F0 animals: M: 126 g F: 109 g M & F Diet (ad libitum) and in milk during non-weaned period for pups 2-generation study: F0, F1 & F2 generations Test material: ≥ 99% purity methiocarb Mean daily active-intake/animal of F0 & F1 (mg/kg bw/d), per treatment: F0 F1 0 ppm: M & F 0 0 50 ppm: M 4.6 5.6 F 6.9 7.6 150 ppm: M 14.8 16.3 F 21.3 22.3 Feed Altromin® 1321 meal + 1% peanut oil (DAB 10) Conclusions: NOAEL reproductive toxicity = 500 ppm: M = 55.1 & F = 83.9 [highest test dose] NOAEL parental toxicity: could not be set: At all doses for parental males, decreased erythrocyte AChE NOAEL offspring toxicity = 150 ppm: M = 14.8 & F = 21.3 [LOAEL = 500 ppm: decreased pup weight, lactation index & litter size] Eiben, R. & Bach, U. (2002c) 23-October-2002 (Study No.: T 6070 298 Report-No: AT00047 Document No.: AT00046 / MO-02-0015935 Record No.: MO-02-0015935 / M-064945-01-1)
* : U = Unknown n = 10/sex/dose/generation Developmental Toxicity Rat Wistar (Hannover) BR Age: F: 15 w 2 d Mean body weight females: 211.6–214.0 g F only Oral gavage Test material: ≥ 99% purity methiocarb Doses: 0, 0.5, 1.5 or 5 5 mg/kg bw/d n = 30 0.5% Carboxy- Methyl- cellulose and 0.4% Tween 80 in deionized water Conclusions: Maternal NOAEL: 0.49 mg/kg bw/d LOAEL = 1.49 based on muscle fasciculations Developmental NOAEL: >5 mg/kg bw/d [LOAEL: >5] Young, A.D. 18-Jan-2002 (Study No.: 01-T12-DV Report-No: 10923 Document No.: 01-T12-DV / M-038693-01-1) Dermal absorption Species Strain, age, weight Sex Route Test parameters (e.g. dose) Vehicle Toxicology conclusion/s Reference information Rat & human Sprague Dawley 25 d M & F Dermal absorption (in vitro) Methiocarb µg /cm2 4738.4 2283.4 (repeat) 5.51 FS*(High dose) FS (mid dose) FS (low dose) Results: Relative 24 h skin absorption (%) via epidermis: Maas, W.J.M. 9-Nov-2001 (TNO Report No.: V 3859
[Abdomen] epidermal membranes (dermatomed skin)] n = 5 (rat) n = 5 (human) [3 donors] Exposure time: 8 h [Swab-washes of skin at 8 h & 24 h] Exposure area = 1 cm2 Measure of methiocarb: in skin, at 24 h; on skin, at 8 & 24 h Radio-Labelled active used: ≥ 99% Comments: Approximately 92% of dose was not absorbed, for both rat and human. Percent recovery* was ~92% for human and ~93% for rat. * recovery = surface + skin + receptor compartments MO-05-008896 Record No.: M-251996-01-1) Rat Wistar HsD Cpb:WU (Albino) 9–10 wk (young adult) M Dermal absorption (in vivo) Methiocarb Single dose to exposure areas: 2 x 30 mg/dust = 5.04 mg Dose; 420 µg per cm2: n = 4 Exposure area = ~ 2 x 6 cm2 Exposure time: 8 h Corn dust contaminated with [14C]-methiocarb (0.084 mg/mg- dust [nominal]) Radio-labelled active used: > 99% Results: Skin absorption % at 8–168 h after application of 420 µg/cm2: 8 h 24 h 72 h 168 h Direct* 0.631% 2.577% 5.268% 7.819% Total 6.711% 5.130% 8.016% 9.150% Potential** * = systemic compartment (e.g. excreta, blood) Muriel Odin Feurtet 11-March-2005 (Study ID: SA 04293 Document No.: SA 04293/ MO-05-005737)