Application for the Reassessment of a Hazardous Substance under ...

“Inhalational NOEL for Occupational Exposure Assessment―Due to the volatile nature of dichlorvos, there is highly significant potential for productusers to be exposed via inhalation, especially during spray application. For productusers, the frequency of inhalation exposure in an occupational setting would be thesame as for dermal exposure, as discussed above. Persons exposed occupationally intreated buildings are likely to be exposed by inhalation repeatedly on successive days.―Several short-term studies have been undertaken in which ChE activity was measuredin humans exposed to dichlorvos by inhalation. However, their usefulness is limited byuncertainty concerning the NOECs and/or the airborne concentrations of dichlorvos towhich the subjects were exposed. It is therefore necessary to perform the assessmentusing studies carried out by oral administration. As discussed previously, the mostsuitable study for estimation of occupational risks is that of Rider (1967), in which theNOEL was 0.014 mg/kg bw/d[ay]. Adjusting for the inhalation absorption factor of70%, the resulting NOEL becomes 0.02 mg/kg bw/d[ay]. This value should be used forrisk assessment of professional users during application and on restricted entry intotreated areas. The acceptable margin of inhalation exposure (MOE) is > 10, resultingfrom application of a 10-fold uncertainty factor for intraspecies variability.‖ (APVMA,2008b)Key Study:“Rider JA (1967) Determination of the minimal incipient toxicity of dichlorvos inhumans. Report and Study no. unspecified. Lab: Gastrointestinal Research Laboratory,Franklin Hospital, San Francisco, CA, USA. Sponsor: Shell Chemical Company,Agricultural Chemicals Division, New York, New York, USA. Report date: October1967.Materials and Methods―Dichlorvos (unspecified source, Batch/Lot No. & purity), formulated in corn oil, wasadministered to ―healthy young men‖ in gelatine capsules at 1.0, 1.5, 2.0 or 2.5mg/d[ay] for 28 days (equivalent to 0.014, 0.021, 0.029 and 0.036, respectively,assuming an average bodyweight of 70 kg). The doses were split between two capsules,which were ingested at 8 am and 3 pm. Few details were given regarding the subjects(such as age and bodyweight) other than that they were serving sentences at theCalifornian Medical Facility, Vacaville, California, USA. Each subject was physicallyexamined and interviewed prior to the commencement of dosing. At each dose, 4 or 5subjects received the capsules containing dichlorvos, while 2 control subjects receivedcapsules containing only corn oil. An additional group of subjects received 0 (n=2) or1.5 mg/d[ay] (n=10) dichlorvos over 60 days followed by a recovery period of 74 days.Analysis of the concentration and stability of dichlorvos was not performed.―All subjects were interviewed on a weekly basis and any symptoms recorded. Baselineplasma and RBC ChE activities were analysed over a 14-28 day period prior to dosingusing the potentiometric method of Michel (1949), which measures the ΔpH/h. Plasmaand RBC ChE activities were analysed 24 hours after the first dose and then twiceweekly throughout the study. In the additional group of subjects dosed with 1.5mg/d[ay], plasma and RBC ChE activities were measured during the 74-day recoveryperiod. The following clinical chemistry parameters were measured prior to treatmentDichlorvos reassessment – application Page 271 of 436