Registration Dossier
Registration Dossier
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EC number: 220-864-4 | CAS number: 2921-88-2
Direct observations: clinical cases, poisoning incidents and other
Administrative data
- Endpoint:
- direct observations: clinical cases, poisoning incidents and other
- Type of information:
- other: PBPK Model
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Chlorpyrifos: Revised Human Health Risk Assessment for Registration Review
- Author:
- UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
- Year:
- 2 014
- Bibliographic source:
- EPA OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION Document D424485
- Report date:
- 2014
- Reference Type:
- publication
- Title:
- Chlorpyrifos: Third Revised Human Health Risk Assessment for Registration Review
- Author:
- UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
- Year:
- 2 020
- Bibliographic source:
- US EPA OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION Document D456427
- Report date:
- 2020
Materials and methods
- Study type:
- other: PBPK-PD model
- Endpoint addressed:
- repeated dose toxicity: inhalation
- repeated dose toxicity: dermal
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- The PBPK-PD model for chlorpyrifos that was originally developed by Timchalk and coworkers in 2002 (Timchalk et al., 2002a, b) has been refined over the years as more data has become available (Busby-Hjerpe et al., 2010; Cole et al., 2005; Garabrant et al., 2009; Lee et al., 2009; Lowe et al., 2009; Lu et al., 2010; Marty et al., 2007; Timchalk and Poet, 2008; Timchalk et al., 2005; Timchalk et al., 2006). In recent collaborative research effort between Battelle Pacific Northwest National Laboratory and Dow (DAS et al., 2011; Poet et al, 2014; MRIDs 49074901, 48913401), the chlorpyrifos PBPK-PD model has been expanded from the ‘typical adult’ model to include other lifestages, specific examples were infants (6 months), children (3 year-olds), and adults (30 year olds). The model has also been used by regulatory agencies such as the US EPA as part of the human health risk assessment of chlorpyrifos (US EPA, 2014, 2020).
- GLP compliance:
- no
Test material
- Reference substance name:
- Chlorpyrifos
- EC Number:
- 220-864-4
- EC Name:
- Chlorpyrifos
- Cas Number:
- 2921-88-2
- Molecular formula:
- C9H11Cl3NO3PS
- IUPAC Name:
- O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate
- Test material form:
- solid
Constituent 1
Method
- Route of exposure:
- inhalation
Results and discussion
- Outcome of incidence:
- The resulting occupational (adult human) POD values corresponding to 10% RBC AChE inhibition set by the US EPA for dermal and inhalation exposures are 3.63 mg/kg bw/d and 0.138 mg/kg bw/day respectively. The inhalation point of departure can be expressed as 0.966 mg/m3 when taking into account the default body weight of 70 kg and a respiratory rate associated with a volume of light activity for a worker of 10m3/day cited in the REACH guidance document (ECHA, Chapter R8).
For the long-term inhalation assessment, the NOAEC would be 0.966 mg/m3. No further modification of the POD (or human NOAEC) is required prior to the incorporation of assessment factors.
Applicant's summary and conclusion
- Conclusions:
- occupational (adult human) POD value corresponding to 10% RBC AChE inhibition for inhalation = 0.138 mg/kg bw/day
occupational (adult human) POD value corresponding to 10% RBC AChE inhibition for dermal exposure = 3.63 mg/kg bw/d - Executive summary:
The PBPK-PD model was used recently to estimate exposure levels resulting in 10% RBC AChE inhibition in workers following steady state occupational exposures. For occupational handlers (and post-application workers), the dermal Point of departure (POD) was estimated for humans (workers) using the PBPK-PD model and assuming a body weight of 69 kg (to represent a female aged 13-49), 100% of the skin’s surface was exposed for 5 days/week, and the exposure duration was 8 hours/day for 21 days. For occupational handlers, the inhalation POD was estimated based on assumed exposures for 8 hours/day, 5 days/week, for 21 days.
The resulting occupational (adult human) POD values corresponding to 10% RBC AChE inhibition set by the US EPA for dermal and inhalation exposures are 3.63 mg/kg bw/d and 0.138 mg/kg bw/day respectively. The inhalation point of departure can be expressed as 0.966 mg/m3when taking into account the default body weight of 70 kg and a respiratory rate associated with a volume of light activity for a worker of 10m3/day cited in the REACH guidance document (ECHA, Chapter R8).
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