Appendix 1: 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. No further information known |
@ 10-6: 1-8 µg/L @ 10-5: 10-80 µg/L |
These estimates are similar to those derived from epidemiological data, which formed the basis for the previous guideline value of 10 µg/L associated with a 10-5 excess lifetime cancer risk. |
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