Benchmark Dose Software (BMDS)

# V. BMD Problems

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*You need to answer all of the questions in this section to complete
the BMDS Crossnumber Puzzle and obtain the final certificate.*

**Download and Install BMDS****Dichotomous Data**- After installing BMDS, start the program by double-clicking on the BMDS icon on your computer desk top, and open a "New" (blank) data entry spreadsheet.
- Enter the following data into the BMDS spreadsheet:
- Run a 1st, 2nd and 3rd degree multistage polynomial model on this data, restricting the beta coefficients to be = 0.
- What does the 3rd degree multistage model give as a BMDL? (3 Across) AIC? (5 Across)
- What is the AIC for a 2nd Degree Multistage model run? (5 Down)
- What is the AIC for a 1st Degree Multistage model run? (8 Across)
- Which of the three BMDL values would you use? (4 Across)
- Enter the following dichotomous data into another blank spreadsheet.
- Run the "restricted" Log-Probit and Weibull models on this data.
- Which BMDL value would you use if a linear mechanism of action were suspected for this endpoint? (2 Across)
**Nested Dichotomous Data**

In a 1993 paper, Rogers, et al. describe a Log-Logistic BMD analysis of the developmental effects of methanol on CD-1 mice.- Using Rogers et al. dose-response data for cervical rib (Download Here) and the BMDS NLogistic model, can you duplicate their results (below)? What is the AIC value associated with this model run? (3 Down; Hint: Use 5% added risk, drop the high dose and don't use litter specific covariate.)
- Run the NLogistic model on the cervical rib used by Rogers, et al. using litter size as the litter specific covariate. What is the lowest AIC you can achieve? (7 Down)
**Continuous Data**

Follow the instructions on the BMDS web home page to download the latest version of BMDS to your computer. What directory is the WGNUPL32.exe file located in after the BMDS installation is completed? (1 Down)

DOSE | N | RESPONSE |
---|---|---|

0 | 50 | 0 |

1000 | 50 | 2 |

3000 | 50 | 6 |

8000 | 50 | 25 |

DOSE | N | RESPONSE |
---|---|---|

0 | 86 | 1 |

0.55 | 81 | 19 |

1.20 | 81 | 54 |

x2 | Log-Likelihood | Model Parameters | 5% Added Risk | ||||
---|---|---|---|---|---|---|---|

Alpha | Beta | Gamma | BMD | BMDL | |||

Cervical Rib | .160 | -519.7 | .2960 | -13.7 | 1.66 | 824 | 305 |

Below is a table from an NTP chronic inhalation study of rats reporting hematological effects in females. Model both endpoints using the polynomial model. Assume that no consensus could be reached regarding the level of change in these endpoints that would constitute adversity. What BMDL would you use as your point of departure? (6 Across; Hint: Consider dropping high doses to achieve adequate model fit.)

Selected Hematology Data for Rats in the 14-Week Inhalation Study

Chamber Control | N | 31 ppm | 62.5 ppm | 125 ppm | 250 ppm | 500 ppm | |
---|---|---|---|---|---|---|---|

Erythrocytes (10E6/µ L) | 8.48 ± 0.05 | 10 | 8.08 ± 0.07** | 7.70 ± 0.08** | 6.91 ± 0.05** | 6.07 ± 0.04** | 4.77 ± 0.15** |

Retriculocytes (10E6/µ L) | 86 | 10 | 0.10 ± 0.01 | 0.16 ± 0.02 | 0.26 ± 0.04* | 0.34 ± 0.04** | 0.40 ± 0.11** |

*** Significantly different (P <= 0.05) from the
chamber control group by Dunn's or Shirley's test
** P <= 0.01**

**Problems
Crossnumber Quiz**

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