Table 2.
Ranges in no observed effect level (NOEL) and lowest observed effect level (LOEL) for 25 chemicals with ≥2 Hershberger studies included after the second exclusion filter was applied (see text and Table 1 for details.
| Chemical/study design (n=number of studies) | NOEL (mg/kg bw/d) | LOEL (mg/kg bw/d) | # Pos/Neg results | OECD reference classification |
|---|---|---|---|---|
| p,p’-DDE (n=56) | 10–50 | 5–200 | Anti-androgenic | |
| Guideline* (n= 29) | 10–50 | 16–200 | 29/0 | |
| Stimulated weanling (n=9) | 16–50 | 5–160 | 9/0 | |
| Other models (n=18) | 10–30 | 30–200 | 18/0 | |
| flutamide (n=32) | 0.15–0.6 | 0.1–100 | Anti-androgenic | |
| Guideline (n=18) | - | 1–100 | 18/0 | (AR antagonist) |
| Stimulated weanling (n=2) | - | 0.1–3 | 2/0 | |
| Other (n=12) | 0.15–0.6 | 0.6–100 | 12/0 | |
| finasteride (n=28) | 0.002–0.2 | 0.008–25 | Anti-androgenic | |
| Guideline (n=19) | 0.002–0.2 | 0.008–25 | 19/0 | (5αR inhibitor) |
| Stimulated weanling (n=7) | 0.008 | 0.04–25 | 7/0 | |
| Other (n=2) | - | 25 | 2/0 | |
| linuron (n=18) | 10–100 | 10–100 | Anti-androgenic | |
| Guideline (n=11) | 10–100 | 10–100 | 10/1 | |
| Stimulated weanling (n=7) | 10–30 | 100 | 7/0 | |
| Other | - | - | ||
| 17-methyl testosterone (n=20) | 0.1–20 | 0.5–100 | Androgenic | |
| Guideline (n=12) | 0.1–10 | 0.5–50 | 12/0 | |
| Stimulated weanling | - | - | ||
| Other (n=8) | 0.5–20 | 5–100 | 8/0 | |
| vinclozolin (n=20) | 3–30 | 10–100 | Anti-androgenic | |
| Guideline (n=10) | 3–30 | 10–100 | 10/0 | |
| Stimulated weanling (n=2) | - | 30 | 2/0 | |
| Other (n=8) | 3–10 | 10–100 | 8/0 | |
| procymidone (n=14) | 3–30 | 3–100 | Anti-androgenic | |
| Guideline (n=11) | 3–10 | 3–100 | 11/0 | |
| Stimulated weanling (n=2) | 3–30 | 10–100 | 2/0 | |
| Other (n=1) | 3 | 10 | 1/0 | |
| trenbolone (n=11) | 1.5–100 | 8–200 | Androgenic | |
| Guideline (n=10) | 1.5–10 | 8–50 | 10/0 | |
| Stimulated weanling | - | - | ||
| Other (n=1) | 100 | 200 | 1/0 | |
| 4-nonylphenol (n=9) | 160–200 | 160 | Negative | |
| Guideline (n=9)* | 160–200 | 160 | 1/8 | |
| Stimulated weanling | - | - | ||
| Other | - | - | ||
| dibutyl phthalate (n=7) | 500 | 500–1000 | NA | |
| Guideline (n=6) | 500 | 500–1000 | 5/1 | |
| Stimulated weanling | - | - | ||
| Other (n=1) | 500 | 1000 | 1/0 | |
| 2,4-dinitrophenol (n=8) | 10 | - | Negative | |
| Guideline (n=8)† | 10 | - | 0/8 | |
| Stimulated weanling | - | - | ||
| Other | - | - | ||
| testosterone propionate (n=6) | 0.02–0.1 | 0.0125–0.25 | Androgenic | |
| Guideline (n=4) | 0.02–0.1 | 0.0125–0.2 | 4/0 | |
| Stimulated weanling | - | - | ||
| Other (n=2) | 0.06 | 0.1–0.25 | 2/0 | |
| prochloraz (n=4) | 62.5 | 50–250 | NA | |
| Guideline (n=1) | 62.5 | 125 | 1/0 | |
| Stimulated weanling | - | - | ||
| Other (n=3) | 50–250 | 3/0 | ||
| testosterone (n=3) | 0.1 | 0.05–0.2 | - | NA |
| Guideline | - | - | - | |
| Stimulated weanling | - | - | - | |
| Other (n=3) | 0.1 | 0.05–0.2 | 3/0 | |
| fenarimol (n=3) | 200 | NA | ||
| Guideline | - | - | - | |
| Stimulated weanling | - | - | - | |
| Other (n=3) | - | 200 | 3/0 | |
| cyfluthrin (n=3) | 6–20 | 18–50 | ||
| Guideline (n=1) | 20 | - | 0/1 | NA |
| Stimulated weanling | - | - | ||
| Other (n=2) | 6 | 18–50 | 2/0 | |
| permethrin (n=3) | 120 | 10–50 | ||
| Guideline (n=1) | 120 | - | 0/1 | NA |
| Stimulated weanling | - | - | - | |
| Other (n=2) | - | 10–50 | 2/0 | |
| 3-(dibutyliamino)phenol (n=3) | NA | |||
| Guideline (n=3) | 400 | - | 0/3 | |
| Stimulated weanling | - | - | ||
| Other | - | - | ||
| methyl-1-testosterone (n=2) | 0.03 | 0.3–1 | NA | |
| Guideline (n=1) | 0.03 | 0.3 | 1/0 | |
| Stimulated weanling | - | - | ||
| Other (n=1) | - | 1 | 1/0 | |
| beta-cyfluthrin (n=2) | 12 | 36–50 | NA | |
| Guideline | - | - | ||
| Stimulated weanling | - | - | ||
| Other (n=2) | 12 | 36–50 | 2/0 | |
| bis(2-thylhexyl)phthalate (DEHP) (n=2) | 20–100 | 100–200 | ||
| Guideline (n=1) | 20 | 100 | 1/0 | NA |
| Stimulated weanling | - | - | ||
| Other (n=1) | 100 | 200 | 1/0 | |
| 2,4,4’-trihydroxy benzophenone (n=2) | 100–600 | 300 | ||
| Guideline (n=1) | 600 | - | 0/1 | NA |
| Stimulated weanling | - | - | ||
| Other (n=1) | 100 | 300 | 1/0 | |
| bifenthrin (n=2) | ||||
| Guideline (n=1) | 10 | - | 0/1 | NA |
| Stimulated weanling | - | - | ||
| Other (n=1) | - | 13.5 | 1/0 | |
| 3-amino-1,2,4-triazole | ||||
| Guideline (n=2) | 1000 | - | 0/2 | NA |
| Stimulated weanling | - | - | ||
| Other | - | - | ||
| 4,4’-butylidenebis(2-tert-butyl-5-methylphenol) (n=2) | ||||
| Guideline (n=2) | 1000 | - | 0/2 | NA |
| Stimulated weanling | - | - | ||
| Other | - | - |
“Guideline” studies closely followed the OECD 441/EPA 890.1350 guideline (i.e. males were castrated between postnatal day (PND) 42 and 53, allowed ≥ 7 d post-surgery, dosed for 10 d). “Stimulated weanling” studies were conducted on uncastrated males, stimulated with an androgen and treated with test chemical. “Other models” deviated from the guideline study (e.g. castrated before or after PND 42–53, dosed <10 d, dosing began <7 d after castration), but adhered to criteria for evaluating positive and negative study results defined in Table 1.
4-nonylphenol and 2,4-dinitrophenol were included as negative chemicals and were typically only tested at a single dose in the androgenic or anti-androgenic study designs. Thus, though all other criteria are met, they do not meet the requirements for minimum test chemical doses with the exception of one study for 4-nonylphenol that tested three doses (in which the test chemical was inactive).