English: International Guidelines for the Ingestion of Benzene Regulatory Agency Pivotal Study Endpoint (cancer/non-cancer) Quantitative Assessment (SF/ Linear extrapolation/oral slope factor) Guideline Comments Health Canada (1991) Food and Beverage NTP, 1986 2 year (corn oil gavage) 5 days/week using rats and mice Overall Carcinogenicity; Mouse LOAEL 25mg/kg bw/day (5 day/week) conversion for 7 days/week ˜ 18 mg/kg bw/d SF 5000-fold (overall) Additional 10-fold (food and bev) TDI(overall) 3.6 µg/kg bw/d TDI (food and bev.) 0.36 µg/kg bw/d For comparison FDA (1991) -Tollefson et al. used the NTP 1986 carcinogenic mouse data to derive a unit risk value of 4.0 x10-2 (mg/kg bw/d)-1 from the collective unit risk values for male and female mice @ 10-6: 0.025 µg/kg bw/d The Health Canada (1991) virtually safe dose (VSD) calculation was 0.045 µg/kg bw/d EPA (IRIS 2003) Chronic Oral Exposure Rothman et al., 1996 Human occupational study of 44 workers via inhalation over a range of 0.7-16 years Non-carcinogenic endpoint based on decreased lymphocyte count BMDL(?) 1.2 mg/kg/day was derived by route-to-route extrapolation with the assumptions that inhalation absorption was 50% and oral absorption was 100% Uncertainty Factor (UF) 300 RfD (TDI) 4.0 µg/kg bw/d Comparison to NTP study for non-cancer endpoint used mouse LOAEL of 18 mg/kg bw/d and an UF of 3000 (10x10x10x3) RfD (TDI) 6 µg/kg bw/d Comparison analysis based on BMDLADJ used BMD modeling of male rat data and an UF 1000 (3x3x10x10) RfD (TDI) 0.7 µg/kg bw/ RIVM (2001) Oral Rinsky et al., 1987 Analysis of a human occupational cohort study of 748 men via inhalation for at least one day over 9 years Carcinogenic endpoint based on leukemia A maximum permissible risk concentration of 20 µg/m3 was derived from the Rinsky analysis; route-to-route extrapolation with the assumptions that inhalation absorption was 50% and oral absorption was 100% Oral maximum permissible risk dose @ 10-4: 3.3 µg/kg bw/d RIVM considers this oral MPR to be "provisional because it was derived using route-to-route extrapolation, a procedure involving considerable uncertainty." EPA Drinking Water Rinsky et al., 1981, 1987 Carcinogenic endpoint based on leukemia Route-to-route linear extrapolation using an oral slope factor of 1.5x10-2 to 5.5x10-2 (mg/kg/day)-1 to derive a drinking water unit risk of 4.4x10-7 to 1.6x10-6 (µg/L)-1 @ 10-6: 1-10 µg/L Using the oral slope factor @ 10-6: 0.018 - 0.066 µg/kg bw/d Health Canada (1987) Drinking Water NTP, 1986 Carcinogenic endpoints using data for leukemia/lymphomas in female mice and oral cavity squamous cell carcinomas in male rats as the outer boundaries for risk calculation Derived unit lifetime risk associated with 1 µg/L ingestion of benzene in drinking water range from 6.1x10-7 (leu/lym in f.m) to 6.7x10-6 (oral carc m.r) MAC 5 µg/L The estimated lifetime risk (3.1x10-6 to 3.4x10-5) associated with the ingestion of drinking water containing 5 µg/L benzene is within a range that is considered by the authors of the report to be "essentially negligible" WHO (2004) Drinking Water NTP, 1986 Carcinogenic endpoints based on leukemia/lymphomas in female mice and oral cavity squamous cell carcinomas in male rats A robust linear extrapolation model was used, as there was a statistical lack of fit of some of the data with the linearized multistage model.
French: US-EPA Eau potable Rinsky et coll., 1981, 1987 Aboutissant carcinogénique basé sur la leucémie Extrapolation linéaire voie-à-voie utilisant un facteur de pente oral de 1,5 x 10-2 à 5,5 x 10-2 (mg/kg/j)-1 pour tirer un risque pour l'eau potable de 4,4 x 10-7 à 1,6x10-6 (µg/l) -1 à 10 -6 : 1-10 µg/l Utilisant un facteur de pente oral à 10-6 : 0,018 - 0,066 µg/kg pc/j Santé Canada (1987) Eau potable NTP, 1986 Aboutissants carcinogéniques utilisant des données pour la leucémie / lymphomes chez le carcinome des cellules squameuses de la cavité buccale chez les rats mâles comme limites extérieures pour le calcul du risque A tiré un risque à vie unitaire associé à l'ingestion de 1 µg/l de benzène dans l'eau potable de 6,1 x 10-7 (leu/lym chez les souris femelle) à 6,7 x 10-6 (carcinome oral chez les rats mâles) CMA 5 µg/L Le risque estimé à vie (3,1 x 10-6 à 3,4 x 10-5) associé à l'ingestion d'eau potable contenant 5 µg/l de benzène est à l'intérieur des valeurs considérées par les auteurs du rapport comme « essentiellement négligeables » OMS (2004) Eau potable NTP, 1986 Aboutissants carcinogéniques basés sur la leucémie /lymphomes chez les souris femelles et les carcinomes des cellules squameuses de la cavité orale chez les rats mâles Un modèle d'extrapolation linéaire robuste a été utilisé, car sur le plan statistique, certaines données ne cadraient pas avec le modèle à stade multiple linéarisé.