Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.79 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
43.2
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

For calculation of the DNELs the assessment factors (AF) of the ECETOC Technical report no. 86 "Derivation of assessment factors for human health" (2003) were applied. The AF used from the ECETOC Technical report no. 86 for the DNEL calculation for Diuron differ in two points from the AF recommended in the "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose[concentration]-response for human health", ECHA, May 2008. The AF for remaining differences is 1 instead of 2.5 and the AF for intraspecies differences for worker is 3 instead of 5. The AF from the ECETOC Technical report no. 86 were used because there is evidence that association between intra- and inter-species assessment factors is conservative and that the inclusion of a remaining difference factor is unnecessary. ECETOC (2003) analyzed the available data of Freireich et al. (1966), Schein et al. (1979), and Watanabe et al. (1992) and concluded that apart from allometric scaling there is the likelihood of additional variability around the extrapolated dose or predicted NOAEL in humans. However, this additional variability is probably due not only to possible differences in biological sensitivity between species, but also to intraspecies differences. Apart from these aspects, one also has to consider the different endpoints (maximum tolerated dose – MTD - versus toxic dose low - TDL) used for the evaluation of human and animal data. Thus, it is evident that the comparison of ‘toxic doses’ across species is actually a comparison between doses that cause ‘dose-limiting’ toxicity (MTDH) in a sensitive subpopulation of humans (health-compromised, cancer patients) at one extreme and lethality in 10% of the population of otherwise assumed healthy animals (lethal dose - LD10) at the other. This will overestimate the sensitivity of humans in relation to other species, but to an extent which is (largely) unquantifiable. As a consequence, the adjustment of interspecies AF to account for the differences noted in such analyses is not scientifically justified. Therefore, although residual interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability reflecting the inherent interdependency of inter- and intraspecies factors (ECETOC, 2003). For this total (inter- and intraspecies) variability, ECETOC proposed an overall factor of 3 for the workplace and of 5 for the general population. Therefore, a separate residual AF for interspecies is unnecessary because it is already accounted for by the intraspecies assessment factor (Calabrese, 1985; Hattis et al, 1987).  

References

Calabrese, E.J. (1985). Uncertainty factors and interindividual variation. Regul Toxicol Pharmacol 5:190-196. ECETOC (2003). Derivation of Assessment Factors for Human Health Risk Assessment. Technical Report No.86. European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium.

Freireich, E (1966). Quantitative Comparison of Toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Canc Chemotherap Res 50: 219-245.

Hattis, D. et al. (1987). Human variability in susceptibility to toxic chemicals: a preliminary analysis of pharmacokinetic data from normal volunteers. Risk Anal 7:415 - 426.

Schein, P. et al. (1979). The evaluation of anticancer drugs in dogs and monkeys for the prediction of qualitative toxicities in humans. Clin Pharmacol Therap 11: 3-40. Watanabe, K. et al. (1992). Interspecies extrapolation: a re-examination of acute toxicity data.Risk Anal 12: 301-310.  

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

DNELs for general population do not have to be calculated, because there is no consumer exposure to Diuron.