6. Human Health Hazard Summary Table Phthalate Irritation & Repeated Genetic Carcinogenicity Fertility Developmental Toxicity Sensitisation Dose Toxicity Toxicity Toxicity Dibutyl Oral Skin irritation: Oral Two generation study Two generation In vitro In vitro phthalate Rat: Negative in Negative in cell minimal effect Rat: Rat: Rat: LD50 = 6300- (DBP) NOAEL = 152 mg/kg majority transformation NOAEL (F1) = 52-80 (m- NOAEL (F1) = NE 8000 mg/kg bw Eye irritation: bw/d mutagenicity assays f) mg/kg bw/d LOAEL (F1) = 52-80 (m- minimal effect = 752 mg/kg and cytogenicity LOAEL (F1) = 256-385 f) mg/kg bw/d, number ↓ tests bw/d, liver and (m-f) mg/kg bw/d, of live born, pup weight In vivo ↑ ↓ Respiratory kidney weight; No data testicular atrophy and ↓ Rabbit: irritation: hepatocellular lipid seminiferous tubule Gestation In vivo LD50 >20000 minimal effect deposition; Negative in sex- degeneration study Rat: ↑ mg/kg bw palmitoyl-CoA oxidase linked gene NOAEL = 50 mg/kg bw/d Skin activity and T3 levels mutation and LOAEL = 100 mg/kg ↓ Inhalation sensitisation: chromosomal bw/d, seminiferous tubule negative Inhalation aberration Rat: atrophy, retained nipples LC50 15.68 Rat: assays ≥ mg/L/4h NOAEC = 509 mg/m3, systemic effects. = 1.18 mg/m3, local effects in upper respiratory system High doses: kidney, testes effects. PP noted NE: not established; PP: peroxisome proliferation; m-f: male-female; increase; decrease. ↑: ↓: 39
6. Human Health Hazard Summary Table Phthalate Toxicity Irritation & Sensitisation Repeated Dose Toxicity Genetic Toxicity Carcinogenicity Fertility Developmental Toxicity Dibutyl phthalate (DBP) Oral Rat: LD50 = 6300- 8000 mg/kg bw Rabbit: LD50 >20000 mg/kg bw Inhalation Rat: LC50 ≥ 15.68 mg/L/4h Skin irritation: minimal effect Eye irritation: minimal effect Respiratory irritation: minimal effect Skin sensitisation: negative Oral Rat: NOAEL = 152 mg/kg bw/d = 752 mg/kg bw/d, ↑ liver and kidney weight; ↓ hepatocellular lipid deposition; ↑ palmitoyl-CoA oxidase activity and ↓ T3 levels Inhalation Rat: NOAEC = 509 mg/m3, systemic effects. = 1.18 mg/m3, local effects in upper respiratory system High doses: kidney, testes effects. PP noted In vitro Negative in majority mutagenicity and cytogenicity tests In vivo Negative in sex- linked gene mutation and chromosomal aberration assays In vitro Negative in cell transformation assays In vivo No data Two generation study Rat: NOAEL (F1) = 52-80 (m- f) mg/kg bw/d LOAEL (F1) = 256-385 (m-f) mg/kg bw/d, testicular atrophy and seminiferous tubule degeneration Two generation Rat: NOAEL (F1) = NE LOAEL (F1) = 52-80 (m- f) mg/kg bw/d, ↓ number of live born, ↓ pup weight Gestation study Rat: NOAEL = 50 mg/kg bw/d LOAEL = 100 mg/kg bw/d, seminiferous tubule atrophy, retained nipples NE: not established; PP: peroxisome proliferation; m-f: male-female; ↑: increase; ↓: decrease. 39