Report on the Health Effects of Selected Pesticide Coformulants

Table 2: Compilation of toxicological effects and data availability of selected coformulants by end-point. (Oversigt over udvalgte hjælpestoffers toksikologiske effekter og datatilgængelighed opstillet per effekttype). Chemical name Acronym Acute effects Irritation Sensiti- sation Repeated dose toxicity Toxicity to reproduction Mutagenicity Carcinogenicity Manganese (II) sulphate / Manganese (II) sulphide Rat oral: LD₅₀ 275- 1082 Anim inh: 0.7-69 Mn (as dust) No data Hum inh: neurological eff LOAEC 0.14-1.59 Mn (as total dust) Monkeys inh: neurological eff Rats inh: lung inflammation Rats, mouse oral: nephropathy, thyroid and gi hyperplasia 200- 731 Hum inh: decr sperm count and quality Mice oral: sperm abnormalities LOAEL 23 Rats oral: dev LOAEL 33 In vitro: Ames test neg/pos Mamm cells pos In vivo: Micronucleus pos Chromosome aberration pos Sex linked recessive mutation neg Rat, mouse oral (2 yr): Adenomas in pituitary, thyroid, pancreas; carcinomas in pancreas Diammonium sulphate Hum inh: decr pulmonary function LOAEC 1 Rat inh: LC₅₀ >1200 Rat oral: LD₅₀2840- 4250 Mouse oral: LD₅₀ 610-640 Hum inh: resp tract/eye LOAEC 0.5 Rab: no skin/eye No data Hum inh (3 d, 2 hrs/d): pulmonary function NOEC 0.1 Rat inh (4-8 mth): pulmonary eff 0.5-1 Gp inh (20 d): pulmonary eff 1 No data In vitro: neg No data Dimethyl ether DME Hum inh: CNS depression, 157000 Rat inh: LC₅₀ 313000 No data No data Rat inh: liver (increased AST) NOEC 380 Rat inh: dev NOAEC 76000; mat (CNS) NOAEC 2400 In vitro: neg In vivo: neg Rat inh (2 yr): neg up to 48000 Hexamethylene tetramine Hum oral: bladder inflammation Rat oral: LD₅₀ 9200 Hum: skin/eye Rab, gp: mild skin 2% sol Rab, gp: eye 0.1% in product, no eye 0.2% in saline Hum inh: asthma Hum: pos skin 2% sol, neg skin 0.1% in product Gp: one gpmt pos Hum oral: nausea, diarrhoea Rat, mouse, cat oral (13- 104 wk): NOAEL1500, 2500 and 1250, respectively Hum: no abnormalities in 200 newborns exposed during first trimester Rat dams oral: dev NOAEL 2000 Rat oral (20 wk): bw decr pups 2000 (dams + offspring) Dog oral: stillborn pups In vitro: pos, neg In vivo: neg Rat, mouse oral (up to 2 yr): neg 2500 Rat, mouse derm (up to 2 yr): neg 30% sol

Chemical name Acronym Acute effects Irritation Sensiti- sation Repeated dose toxicity Toxicity to reproduction Mutagenicity Carcinogenicity 30% sol, one neg 0.2% sol 31, NOAEL 15, abnormalities in few pups 94 1-Methyl-1,2- ethanediyl dioleate No data Hum inh: heated vapours No data No data No data No data No data Isopropyl myristate Rat inh: lethargy (aerosol 16-20%) Rat oral: LD₅₀ > 13700 Rat derm: LD₅₀ > 5000 Hum skin: no- min (most studies), LOAEC 10% (one study Rab, mouse skin (3-28 d): mod- sev Rab: no skin/eye (Draize) Monkey inh (13 wk): resp tract 0.95-6.7 Hum skin: no (most studies), few pos case reports Gp: neg 0.1% sol Gp inh (4-13 wk): incr lung weights from 10 Monkeys inh (13 wk): macrophage accumulation 0.95-6.7 Rat oral (up to 16 wk): NOAEL 2000 Mouse skin (1/wk, 18 mth): no gross abnormalities (1% sol) In vitro: neg Mouse derm (lifetime): neg undiluted, enhanced carcinogenicity of benzo(a)pyrene Sodium ligninsulphonat e Rat inh: LC₅₀ > 480 Rat oral: LD₅₀ >40000 Mouse oral: LD₅₀ 6000 Anim: eye, skin, upper resp tract No data Gp oral (6 wk): ulceration colon 1700 Rat oral (16 wk): hist changes liver/kidney, incr weight liver/kidney/spleen 10000, NOAEL 2500 No data No oestrogenic effect in vitro No data No data Calciumdodecyl -benzene- sulphonate CaDBS Rat, mouse oral: LD₅₀ about 4000 No data (Possibly skin, eye, resp tract by analogy to LAS) No data No data No data No data No data Ethylene glycol EG Hum oral: min lethal dose 1600 Rat inh: LC₅₀ (1 hr) 10900 Rat, rab, mouse, gp, dog oral: LD₅₀ >2000-15400 Rab derm: LD₅₀ Hum: low skin, low eye, resp Rab: eye, no skin Hum: few case reports Hum inh: resp irr LOAEC 17 Rat oral: kidney NOAEL 200 Rat, mouse oral: reproductive eff NOAEL 1000 (rat), 840 (mouse) Mouse inh: dev NOAEC 1000 Anim oral: dev NOAEL 1000 (rat), 150 (mouse), 2000 (rab) In vitro: neg In vivo: neg Anim oral (2 yr): neg up to 2000 (rat), up to 12000 (mouse)

Chemical name Acronym Acute effects Irritation Sensiti- sation Repeated dose toxicity Toxicity to reproduction Mutagenicity Carcinogenicity 10600 Mouse derm: dev NOAEL 3550 Propylene glycol PG Hum inh, oral: CNS depression, acidosis (high conc/doses) Rodents oral: LD₅₀ 18000-30000 Rab derm: 20800 Hum: slight skin Rat inh: nose bleeding from 160; goblet cell enlargement from 1000 Rab: mild skin, eye Hum: few case reports Hum inh: no eff up to 94 Hum oral (13 mth): CNS depression 114 Rat: (90 d): haematological eff (not dose-related) Dog/cat oral (2 yr /2- 17wk): haematological eff 5000/1100 Rat inh (18 mth): no eff fertility up to 354 Mice oral (14 wk): no eff fertility up to 10000 Rodents oral: no dev up to 1600 In vitro: neg In vivo: neg Rat oral (2yr): neg Mouse derm (120 wk): neg 2- Butoxyethanol EGBE Hum oral: haemolysis high doses Rat inh: LC₅₀ (4 hr) 2200-2400 Rat, rab, mouse, gp oral: LD₅₀ 320-3100 Rab, gp, rat derm: LD₅₀ 400-4800 Hum: eye, skin, resp NOAEC >100 Rab: mod-sev skin, sev eye Hum: neg Gp: neg Hum inh: haemolysis NOEC >3 Rat, mouse inh: haemolysis LOAEC 152 (rat, female mouse), NOAEC 152 (male mouse) Rat, mouse oral: haemolysis LOAEL 69/82 (rat), NOAEL 357 (mouse) Rat, mouse, rab: not toxic to reproductive organs (male, female) Rab, mouse, rab: no reproductive eff Rat, mouse, rab: no dev In vitro: neg In vivo: neg Rat inh (2 yr): neg male, some evidence female up to 615 Mouse inh (2 yr): some evidence up to 1225 1-Methoxy-2- propanol 2PG1ME Hum inh: CNS depression LOAEC 1125 Rat, gp inh: LC₅₀ app 54600 Anim oral: LD₅₀ 5000-10800 Rab derm: LD₅₀ 13000 Anim: CNS depression Hum inh: nose/eye (15 minutes), throat (45 minutes) LOAEC 938 Rat inh (4 hr): resp tract LOAEC 37500 Rab: no-min skin/eye Gp: neg Rat, mouse, rab, gp inh (up to 6 mth): CNS depression, eff liver 5450-21800 Rat, mouse inh (2 yr): eff liver 11250 NOAEC 3750 Dog oral: CNS depression from 920 Rat inh (10 d): no eff testes up to 2250 Mouse oral (25 d): no eff testes up to 2500 Dog oral (14 wk): macrophages in testes and epididymides LOAEL 462 Rat inh: delayed ossification sternebrae pups, and mat 11250 Rab inh: no eff up to 11250 In vitro: neg Rat, mouse inh (2 yr): no eff up to 11250

Chemical name Acronym Acute effects Irritation Sensiti- sation Repeated dose toxicity Toxicity to reproduction Mutagenicity Carcinogenicity Rat oral: delayed ossification skull pups 739 Mouse oral: dev 3300 Rab oral: no eff 924 Diethylene glycol mono-n- butyl ether DEGBE Rat inh: LC₅₀73000 Rat, rab, mouse, gp oral: LD₅₀ 2000- 9600 Rat, rab derm: LD₅₀ >2000 Hum: skin, eye, resp Rab, gp: low skin, mod eye Hum: few case reports Gp: neg Rat inh: systemic/local eff NOAEC 95 Rat oral: haematological eff LOAEL 50 Rat derm: systemic eff NOAEL 2000, local eff NOAEL 100-200 Rat oral/derm: reproductive eff NOAEL 1000 (oral), NOAEL 2000 (derm) Rat, mouse oral/derm: dev NOAEL 633 (rat, oral), 2050 (mouse, oral), 1000 (rab derm) In vitro: neg In vivo: neg No data Dipropylene glycol monomethyl ether DPGME Rat inh: narcosis 3080 Anim oral: LD₅₀ 5000-7500 Rab derm: LD₅₀ 9400->19000 Hum: eye 20% sol, resp 456, no skin Rab: eye, no skin Hum: neg Rat inh (6-8 mth): CNS depression LOAEC 1848 Anim inh (6-8 mth): slight liver eff LOAEC 1848 Rat, rab inh (90 d): NOAEC 1232 Rat derm (28 d): NOAEL 1000 Rab derm (90 d): NOAEL 4700 Rat, rab inh (90 d): no eff testes up to 1232 Rat, rab inh: no dev up to 1756 In vitro: neg No data Polyethylenegly col- dodecylether PolyEGD E Rat oral: LD₅₀ 4150/8600 Hum: mod skin Rab: mild-mod skin 75-500 (different chain lengths), mod eye Rat: mucous membranes No data No data No data In vitro: neg In vivo: neg No data Cyclohexanone Rat inh: LC₅₀ 6200- 32500 Rat oral: LD₅₀ 1296- 3460 Rab derm: LD₅₀ 794-3160 Hum: eye, nose, throat from 306; skin from 162 Anim: skin, eye Hum: one case report Mouse, gp: neg Hum (14 yr): CNS symptoms LOAEC 162 Rat, rab inh/oral: CNS symptoms Rat inh: male fertility reduced at 5712, NOAEC 2040 Rat, mouse inh: slight dev at 5712, mat at 5712 In vitro: overall neg In vivo: neg Rat, mouse oral: incr incidence of some tumours, relevance questionable

Chemical name Acronym Acute effects Irritation Sensiti- sation Repeated dose toxicity Toxicity to reproduction Mutagenicity Carcinogenicity Hum, anim: CNS depression 1-Methyl-2- pyrrolidone NMP Rat inh: LC₅₀3100- 8800 Rat oral: LD₅₀ 3600- 7900 Rat derm: LD₅₀ 2500-10000 Hum: sev eye 3 (vapour), skin irr Rab: eye Hum: neg Gp: neg Rat inh (2 yr): NOAEC 400 (vapour) Rat inh/oral: testis damage NOAEC 1000, NOAEL 1033 Rat inh/oral: reproductive eff NOAEC 480, NOAEL 160 Anim inh/oral/derm: dev NOAEC 350 (rat) 1000 (rab); NOAEL (oral) 330 (rat), 175 (rab); NOAEL (derm) 500 (rat), 1000 (rab); neurobehavioural teratology LOAEC 620 In vitro: neg In vivo: neg Rat inh (2 yr): neg up to 400 4-Hydroxy-4- methyl-2- pentanone HMP Rat inh: LC_Lo4830 Rat oral: LD₅₀ 2520- 4000 Rab derm: LD₅₀ 13750 Hum inh: eye, nose throat at 483, skin defatting Rab: mild eye skin No data Rat inh (6 wk): CNS depression, eff liver, kidney (male) No data In vitro: neg No data