Table 2.
Studies involving human volunteers evaluated by the JMPR*
| Compound | Group | Year | Number of toxicity studies | Number of ADME studies | Used for ADI | Used for ARfD | Comments |
|---|---|---|---|---|---|---|---|
| Carbaryl | Carb-amate | 1996 | 3 | 1 (same study) | NO | NO | Carcinogenicity in mice |
| Dimethoate | OP | 1996 | 1 (1967) | NO | NO | Reproductive toxicity | |
| Mevinphos | OP | 1996 | 2 (1975) | YES | YES | SF of 20 because N = 8 | |
| Fenthion | OP | 1997 | 1 (1979) | YES (in 1995) | NO | Not suitable for ARfD because no effects in rats after a single much higher dose | |
| Malathion | OP | 1997 | 1 (1962) | NO | NO | Old study, possibly containing impurities, NOAEL in rats much higher | |
| Methidathion | OP | 1997 | 1 (1970) | NA | YES | SF of 10 despite N = 8 because supported by data in rats with a SF of 100 | |
| Amitraz | 1998 | 3 (1984) | 1 (1984) (same study) | NA | YES | ||
| Dichloran | 1998 | 1 (1962) | NO | NA | Supportive of data in dogs with a SF of 200 because of data gaps | ||
| Chlorpyrifos | OP | 1999 | 7 (1971-1999) | 1 (1999) (same study) | YES | YES | ADI based on data in animals with a SF of 100 and in humans with a SF of 10 (N = 4-6) giving the same ADI |
| Ethoprophos | OP | 1999 | 1 (1986) | 1 (1986, same study) | NA | NA | Study performed to assess occupational exposure |
| Permethrin | Pyre-throid | 1999 | 1 (1985) | NO | NA | ||
| Fenitrothion | OP | 2000 | 3 (1968-1999) | 1 (1999) (same study) | NO | YES | Too short duration (4 days) for setting the ADI |
| Imazalil | Azole | 2000 | 1 (1979) | NO | NA | Skin irritation study | |
| Diazinon | OP | 2001 | 2 (1999) | NA | NO | Only in male and studies in animals showed sex difference | |
| Methomyl | Carbamate | 2001 | 1 (1998) | YES | YES | SF of 5 because of rapid reversibility of effects, used although N = 5 because supported by data in animals | |
| Acephate | OP | 2002 | 2 (1972-2000) | 1 (2000) (same study) | NO | NO | Not used because brain AChE more sensitive to inhibition than RBC AChE |
| Ethephon | 2002 | 3 (1971-1977) | NA | YES | |||
| Methamidophos | OP | 2002 | 2 (1973) | NO | NO | Studies considered supportive (giving similar ADI or ARfD) | |
| Oxamyl | Carb-amate | 2002 | 1 (1999) | YES | YES | Although N = 5, data in animals were supportive | |
| Oxydemeton methyl | OP | 2002 | 2 (1973) | NA | NO | Not used because of methodological problems | |
| Tolylfluanid | Sulf-amide fun-gicide | 2002 | 1 (1968) | NA | NA | Skin irritation study | |
| Triazophos | OP | 2002 | 4 (1971-1973) | YES | YES | N = 5-25, acceptable because performed according to the standard of the time | |
| Malathion | OP | 2003 | 1 (2000) | 1 (2000) (same study) | NA | YES | N = 14 |
| Paraquat | 2003 | 1 (1984) | NO | NO | Poor skin absorption | ||
| Phospmet | OP | 2003 | 1 (1999) | NA | YES | N = 12 | |
| Propiconazole | Azole | 2004 | 1 (1991 | NA | NA | Study for skin sensitisation | |
| Acephate | OP | 2005 | 2 (2000-2003) | 2 (2000-2003) (same studies) | YES | YES | N = 7-14, more data on brain vs RBC AChE allowed the use of human data. Comparative metabolism data also allowed the use of a chemical specific assessment factor |
| Pirimiphos-methyl | OP | 2006 | 2 (1974-1976) | NA | NO | Considered supportive since it would have given a slightly lower ARfD | |
| Temephos | OP | 2006 | 1 (1967) | NA | NO | Poor quality of reporting | |
| Thiabedazole | Azole | 2006 | 1 (1965) | NO | NO | Relevant parameters could not be assessed in humans |
* Note: malathion and acephate have been evaluated twice
AChE = Acetyl Cholinesterase
ADME = Absorption, Distribution, Metabolism and Excretion
ADI = Acceptable Daily Intake
ARfD = Acute Reference Dose
NOAEL = No Observed Adverse Effect Level
RBC = Red Blood Cell
SF = Safety Factor