B.4  TOXICITY ASSESSMENT

A.  Introduction

The purpose of the toxicity assessment is to weigh available evidence regarding the potential for particular pesticide active ingredients to cause adverse health effects, and to provide an estimate of the relationship between exposure and the increased likelihood and severity of adverse health effects.[367] EPA has conducted toxicity assessments on most of the pesticide active ingredients found in the pesticides of potential concern (POPCs). Toxicity assessment consists of two steps: hazard identification and dose-response evaluation.

The HRA toxicity assessment was prepared based on the latest information available at the time; however, new information is released on an ongoing basis, which may impact the reliability of some aspects of this report. At the time the toxicity assessment was prepared, EPA’s Office of Pesticide Programs was devoting vast resources to compliance with provisions of the 1996 Food Quality Protection Act (FQPA). Under this Act, OPP is re-evaluating the registration of many pesticide products, assigning the highest priorities to organophosphates (OPs) and carbamates. As a result, OPP is frequently issuing new information on OPs and carbamates.

B.  Hazard Identification

Hazard identification is the process of determining whether exposure to an agent can cause an adverse health effect and whether the adverse health effect is likely to occur in humans. An "adverse" health effect is an indication of unequivocal impairment of health. Adverse health effects may be frank effects and/or laboratory measurements. All the active ingredients in the POPCs have potential adverse health effects in humans by at least one exposure route, as indicated in the human or animal studies listed in Tables 92 through 103. Note that the "critical effects" listed in the tables all indicate a potential for adverse health effects, although not all are adverse health effects per se. Although the critical effects listed in the tables are experimental endpoints, based mainly on animal studies, EPA has determined that these effects are relevant to, and probably occur in, humans. Additional information regarding the hazard identification of the POPCs may be found in the documents cited in the tables, and in the RAND Literature Review.[368]

Table 92. Oral toxicity values - acute/subacute exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descriptionb

Valuec
(mg/kg/day)

Sourced

Additional Basis
and/or Comment

Critical Effect

Test
Species

134-62-3 DEET

NOEL

--  

--

 

extrapolation inappropriate --

--

RfD

--  

extrapolation inappropriate
52645-53-1 Permethrin

NOEL

2.50E+01  

EPA[369]

-- weight loss, temperature, aggression, abnormal motor activity

rat

RfD

2.50E-01 *

--

NOEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 *

--

 

chronic NOEL liver enlargement; hepatocellular effects

dog

RfD

7.10E-02 *

chronic NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

3.00E-01 *

--

 

subchronic NOEL cholinergic poisoning effects

rat

RfD

3.00E-03 *

subchronic NOEL x 1/100
16752-77-5 Methomyl

NOEL

6.00E+00  

EPA[370]

 

-- 1-3 day mortality; neurotoxicity

rabbit

RfD

2.00E-02  

NOEL x 1/300
62-73-7 Dichlorvos

NOAEL

5.00E-01  

EPA[371]

 

-- single dose neurotoxicity

rat

RfD

2.00E-03  

NOAEL x 1/300
2921-88-2 Chlorpyrifos

NOAEL

5.00E-01  

EPA[372]

 

-- plasma cholinesterase inhibition

rat

RfD

5.00E-03  

NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.50E-01  

EPA[373]

 

-- plasma cholinesterase inhibition

rat

RfD

2.50E-03  

NOAEL x 1/100
121-75-5 Malathion

NOEL

5.00E+01  

EPA[374]

 

-- maternal toxicity exhibited

rabbit

RfD

5.00E-01  

NOEL x 1/100
114-26-1 Propoxur

LOEL

1.50E-01  

EPA[375]

 

-- blurred vision, nausea, sweating, increased blood pressure, vomiting, and 40% red blood cell cholinesterase inhibition

human

RfD

5.00E-03  

LOEL x 1/30
22781-23-3 Bendiocarb

NOEL

1.25E-01  

EPA[376]

 

-- whole blood cholinesterase inhibition

rat

RfD

4.16E-04  

NOEL x 1/300
58-89-9 Lindane

NOEL

1.00E+01  

EPA[377]

 

-- no end point was identified indicating the potential for adverse effects after a single dietary exposure

rat

RfD

1.00E-01 *

NOEL x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.

Table 93. Oral toxicity values - subchronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descriptionb

Valuec
(mg/kg/d)

Sourced

Additional Basis
and/or Comment

Critical Effecte

Test
Species

134-62-3 DEET

NOEL

--  

--

extrapolation inappropriate --

--

RfD

--  

extrapolation inappropriate
52645-53-1 Permethrin

NOEL

1.55E+01  

EPA[378]

-- tremors and staggered gait; 13-week feeding study

rat

RfD

1.55E-01 *

NOEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 *

O[379]

chronic NOEL liver enlargement; hepatocellular effects

dog

RfD

7.10E-02 *

chronic NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

3.00E-01  

O[380]

-- blood cholinesterase inhibition; 13-week feeding

dog

RfD

3.00E-03 *

NOEL x 1/100
16752-77-5 Methomyl

NOEL

2.50E+00 *

EPA[381]

chronic NOEL chronic histopathologic kidney lesions

dog

RfD

8.33E-03 *

chronic RfD
62-73-7 Dichlorvos

NOAEL

5.00E-02  *

EPA[382]

chronic NOAEL plasma/RBC/brain cholinesterase inhibition

dog

RfD

5.00E-04 *

chronic RfD
2921-88-2 Chlorpyrifos

NOAEL

2.50E-02  

EPA[383]

-- plasma inhibition at low doses and higher doses exhibited increased brain and heart weight, adrenal gland effects and decreased body weight gain

rat

RfD

2.50E-04  

NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.00E-02 *

EPA[384]

chronic NOAEL pattern of no adverse effects on cholinesterase inhibition

dog

RfD

2.00E-04 *

chronic RfD
121-75-5 Malathion

NOAEL

2.40E+00 *

EPA [385]

chronic NOAEL inhibition of RBC cholinesterase activity

rat

RfD

2.40E-02 *

chronic RfD
114-26-1 Propoxur

NOEL

2.46E+00 *

EPA [386]

chronic NOEL elevated mean cholesterol level

dog

RfD

2.46E-02 *

based on chronic NOEL
22781-23-3 Bendiocarb

NOAEL

1.25E-01  

EPA [387]

-- whole blood cholinesterase inhibition

rat

RfD

4.16E-04  

NOAEL x 1/300
58-89-9 Lindane

NOEL

1.00E+01  

EPA [388]

-- maternal effects in a 10-day feeding study

rat

RfD

1.00E-01 *

NOEL x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.
e) RBC = red blood cell.

Table 94. Oral toxicity values - chronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descriptionb

Valuec
(mg/kg/d)

Sourced

Additional Basis
and/or Comment

Critical Effecte

Test Species

134-62-3 DEET

NOEL

1.00E+02  

EPA[389]

-- decrease food consumption, body weight, 1-year study

dog

RfD

1.00E+00 *

NOEL x 1/100
52645-53-1 Permethrin

NOEL

5.00E+00 

EPA [390]

-- increased liver weight

rat/mouse

RfD

5.00E-02   

NOEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 

O[391]

-- liver enlargement; hepatocellular effects

dog

RfD

7.10E-02 *

NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

2.50E-01   

O[392]

-- blood cholinesterase inhibition, 1 year study

dog

RfD

2.50E-03   

NOEL x 1/100
16752-77-5 Methomyl

NOEL

2.50E+00   

EPA [393]

-- chronic histopathologic kidney lesions

dog

RfD

8.33E-03   

NOEL x 1/300
62-73-7 Dichlorvos

NOAEL

5.00E-02   

EPA [394]

-- plasma/RBC/brain cholinesterase inhibition

dog

RfD

5.00E-04   

NOAEL x 1/100
2921-88-2 Chlorpyrifos

NOAEL

3.00E-02   

EPA [395]

-- significant plasma and red blood cell cholinesterase inhibition

dog

RfD

3.00E-04   

NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.00E-02   

EPA [396]

-- cholinesterase inhibition

dog/rat

RfD

2.00E-04   

NOAEL x 1/100
121-75-5 Malathion

NOAEL

2.40E+00   

EPA [397]

-- inhibition of RBC cholinesterase activity

rat

RfD

2.40E-02   

NOAEL x 1/100
114-26-1 Propoxur

NOEL

2.46E+00   

EPA [398]

-- elevated mean cholesterol level

dog

RfD

2.46E-02 *

NOEL x 1/100
22781-23-3 Bendiocarb

NOAEL

1.25E-01  

EPA [399]

-- whole blood cholinesterase inhibition

rat

RfD

4.16E-04  

NOAEL x 1/300
58-89-9 Lindane

NOEL

4.70E-01  

EPA [400]

-- Liver and spleen effects; increased platelets; chronic feeding study

rat

RfD

4.70E-03  

NOEL x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.
e) RBC = red bllod cell.

Table 95. Dermal toxicity values - acute/subacute exposure; noncarcinogenic effectsa

CAS No.

Active Ingredient

Descriptionb

Valuec (mg/kg/d)

Oral Absorption Factord

Sourcee

Additional Basis and/or Comment

Critical Effect

Test Species

134-62-3 DEET

NOEL

--  

--

--

extrapolation inappropriate --

--

RfD

--  

extrapolation inappropriate
52645-53-1 Permethrin

NOAEL

4.30E+02  

--

O[401]

-- mild skin irritation to no-effect

human

RfD

4.30E+01 *

NOEL x 1/10
26002-80-2 d-Phenothrin

NOEL

4.97E+00 *

0.70

--

chronic oral NOEL x OAF --

--

RfD

4.97E-02 *

chronic oral NOEL x OAF x 1/100
35575-96-3 Azamethiphos

LOEL

2.00E+01 *

--

O[402]

subchronic LOEL cholinergic effects; 21-day percutaneous study

rabbit

RfD

2.00E-02 *

based on subchronic LOEL
16752-77-5 Methomyl

NOEL

9.00E+01  

--

EPA[403]

-- no cholinesterase inhibition; 21-day dermal

rat

RfD

9.00E-01  

NOEL x 1/100
62-73-7 Dichlorvos

NOAEL

6.50E-02 *

0.65

EPA[404]

acute oral NOAEL x OAF cholinergic signs and weight loss; oral developmental study

rabbit

RfD

6.50E-04 *

acute oral RfD x OAF
2921-88-2 Chlorpyrifos

NOAEL

5.00E+00  

--

EPA[405]

-- plasma and red blood cell cholinesterase inhibition; 4-day dermal

rat

RfD

5.00E-02  

NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.13E-01*

0.85

EPA[406]

acute oral NOAEL x OAF plasma cholinesterase inhibition; oral acute neurotoxicity

rat

RfD

2.13E-03 *

acute oral RfD x OAF
121-75-5 Malathion

NOEL

5.00E+01  

--

EPA[407]

-- inhibition of plasma, red blood cell, and brain cholinesterase activity; 21-day dermal

rabbit

RfD

5.00E-01  

NOEL x 1/100
114-26-1 Propoxur

NOEL

1.00E+03  

--

EPA[408]

-- lack of toxic effects; 1 to 7-day dermal

rabbit

RfD

1.00E+01 *

NOEL x 1/100
22781-23-3 Bendiocarb

NOEL

5.00E+01  

--

EPA[409]

-- whole blood cholinesterase inhibition;

21-day dermal

rat

RfD

1.66E-01  

--

EPA[410]

NOEL x 1/300
58-89-9 Lindane

NOEL

9.90E+00 *

0.99

--

acute oral NOEL x OAF no end point was identified from the data which indicated the potential for adverse effects after a single dietary exposure

rat

RfD

9.90E-02 *

acute oral NOEL x OAF x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) Oral absorption factors (OAFs) from Table 105. Used if the dermal value is derived from an oral value. If so, the dermal value = the oral toxicity value x OAF.
e) "O" = other.

Table 96. Dermal toxicity values - subchronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descrip-
tionb

Valuec
(mg/kg/d)

Absorption
Factord

Sourcee

Additional Basis and/or Comment

Critical Effectf

Test
Species

134-62-3 DEET

NOEL

--  

--

--

extrapolation inappropriate --

--

RfD

--  

extrapolation inappropriate
52645-53-1 Permethrin

NOEL

1.09E+01 *

0.70

EPA[411]

subchronic oral NOEL x OAF --  

RfD

1.09E-01 *

subchronic oral NOEL x OAF x 1/100
26002-80-2 d-Phenothrin

NOEL

4.97E+00 *

0.70

--

chronic oral NOEL x OAF --

--

RfD

4.97E-02 *

chronic oral NOEL x OAF x 1/100
35575-96-3 Azamethiphos

LOEL

2.00E+01   

--

O[412]

-- cholinergic effects, 21-day percutaneous study

rabbit

RfD

2.00E-02 *

LOEL x 1/1,000
16752-77-5 Methomyl

NOEL

9.00E+01   

--

EPA[413]

-- no cholinesterase inhibition; 21-day dermal

rat

RfD

  9.00E-01   

NOEL x 1/100
62-73-7 Dichlorvos

NOAEL

3.25E-02 *

0.65

EPA[414]

chronic oral NOAEL x OAF blood cholinesterase inhibition; 13 wk measurement in a 1-year oral study

dog

RfD

3.25E-04 *

chronic oral RfD x OAF
2921-88-2 Chlorpyrifos

NOAEL

2.70E-02 *

0.9

EPA[415]

chronic oral NOAEL x OAF significant plasma and RBC cholinesterase inhibition; 85 to 93-day to 2-year oral

dog

RfD

2.70E-04 *

chronic oral RfD x OAF
333-41-5 Diazinon

NOAEL

1.70E-02 *

0.85

EPA[416]

chronic oral NOAEL x OAF plasma cholinesterase inhibition; 90-day and 1-year oral

dog

RfD

1.70E-04 *

chronic oral RfD x OAF
121-75-5 Malathion

NOEL

5.00E+01   

--

EPA[417]

-- inhibition of plasma, RBC and brain cholinesterase activity; 21-day dermal

rabbit

RfD

5.00E-01   

NOEL x 1/100
114-26-1 Propoxur

NOEL

1.00E+03   

--

EPA[418]

-- lack of toxic effects; 1-week to several months dermal

rabbit

RfD

1.00E+01 *

NOEL x 1/100
22781-23-3 Bendiocarb

NOEL

5.00E+01 

--

EPA[419]

-- whole blood cholinesterase inhibition; 1-week to several months dermal

rat

RfD

5.00E-02  

NOEL x 1/1,000
58-89-9 Lindane

NOEL

9.90E+00 *

0.99

--

subchronic oral NOEL x OAF --

--

RfD

9.90E-02 *

subchronic oral RfD x OAF
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) Oral absorption factors (OAFs) from Table 105. Used if the dermal value is derived from an oral value. If so, the dermal value = the oral toxicity value x OAF.
e) "O" = other.
f) RBC = red blood cell.

Table 97. Dermal toxicity values - chronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descrip-tionb

Valuec
(mg/kg/d)

Absorption
Factord

Sourcee

Additional Basis
and/or Comment

Critical Effectf

Test
Species

134-62-3 DEET

NOEL

--  

--

--

extrapolation inappropriate --

--

RfD

--    

  extrapolation inappropriate
52645-53-1 Permethrin

NOEL

3.50E+00 *

0.70

--

chronic oral NOEL x OAF --

--

RfD

3.50E-02 *

  chronic oral RfD x OAF
26002-80-2 d-Phenothrin

NOEL

4.97E+00 *

0.70

--

chronic oral NOEL x OAF --

--

RfD

4.97E-02 *

  chronic oral NOEL x OAF x 1/100
35575-96-3 Azamethiphos

NOEL

2.50E-01 *

1.00

--

chronic oral NOEL x OAF --

--

RfD

2.50E-03 *

  chronic oral RfD x OAF
16752-77-5 Methomyl

NOEL

2.35E+00 *

0.94

--

chronic oral NOEL x OAF --

--

RfD

7.83E-03 *

  chronic oral RfD x OAF
62-73-7 Dichlorvos

NOAEL

3.25E-02 *

0.65

EPA[420]

chronic oral NOAEL x OAF plasma and RBC cholinesterase inhibition in both sexes and brain cholinesterase inhibition in males

--

RfD

3.25E-04 *

  chronic oral RfD x OAF
2921-88-2 Chlorpyrifos

NOAEL

2.70E-02 *

0.90

EPA[421]

chronic oral NOAEL x OAF significant plasma and RBC cholinesterase inhibition; 85 to 93-days to 2-year oral

dog

RfD

2.70E-04 *

  chronic oral RfD x OAF
333-41-5 Diazinon

NOAEL

1.70E-02 *

0.85

EPA[422]

chronic oral NOAEL x OAF no adverse effects on cholinesterase inhibition; 2-year oral

rat

RfD

1.70E-04 *

  chronic oral RfD x OAF
121-75-5 Malathion

NOEL

4.00E+00   

--

EPA[423]

-- inhibition of plasma cholinesterase activity; combined 42-day dermal

rat

RfD

4.00E-02   

  NOEL x 1/100
114-26-1 Propoxur

NOEL

1.00E+03   

--

EPA[424]

-- lack of toxic effects; several months to lifetime

rabbit

RfD

1.00E+01 *

  NOEL x 1/100
22781-23-3 Bendiocarb

NOEL

1.25E-01   

--

EPA[425]

-- whole blood cholinesterase inhibition; >several months

rat

RfD

4.17E-04   

  NOEL x 1/300
58-89-9 Lindane

NOEL

--  

--

--

data unavailable; no chronic exposure --

--

RfD

--  

a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) Oral absorption factors (OAFs) from Table 105. Used if the dermal value is derived from an oral value. If so, the dermal value = the oral toxicity value x OAF.
e) "O" = other.
f) RBC = red blood cell.

Table 98. Inhalation toxicity values - acute/subacute exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descrip-
tionb

Valuec

Units

Sourced

Additional Basis
and/or Comment

Critical Effecte

Test
Species

134-62-3 DEET

NOEL

--    

mg/kg/d

--

extrapolation inappropriate --

--

RfD

--    

-- extrapolation inappropriate
52645-53-1 Permethrin

NOEL

2.50E+01 *

mg/kg/d

--

acute oral NOEL --

--

RfD

2.50E-01 *

mg/kg/d acute oral NOEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 *

mg/kg/d

--

chronic oral NOEL --

--

RfD

7.10E-02 *

mg/kg/d chronic oral NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

3.00E-01 *

mg/kg/d

--

subchronic oral NOEL --

--

RfD

3.00E-03 *

mg/kg/d subchronic oral NOEL x 1/100
16752-77-5 Methomyl

NOEL

1.37E-01   

mg/L

EPA[426]

value for all exposure durations clinical signs of neurotoxicity/acute

rat

RfD

1.30E-01 *

mg/kg/d NOEL converted to mg/kg/d x 1/300
62-73-7 Dichlorvos

NOAEL

1.00E-01   

mg/kg/d

EPA[427]

-- cholinergic effects (oral); developmental study

rabbit

RfD

1.00E-03 *

mg/kg/d NOAEL x 1/100
2921-88-2 Chlorpyrifos

NOAEL

1.00E-01   

mg/kg/d

EPA[428]

-- plasma and RBC cholinesterase inhibition

rat

RfD

1.00E-03 *

mg/kg/d NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.60E-02   

mg/kg/d

EPA[429]

-- plasma cholinesterase inhibition

rat

RfD

8.60E-05   

mg/kg/d NOAEL x 1/300
121-75-5 Malathion

LOEL

1.00E-01   

mg/L

EPA[430]

-- inhib. plasma, RBC cholinesterase; histopathology in respiratory epithelium

rat

RfD

2.80E-01   

mg/kg/d LOEL converted to mg/kg/d x 1/100
114-26-1 Propoxur

NOEL

2.20E+00   

mg/L

EPA[431]

-- significant plasma, RBC, and cholinesterase inhibition

rabbit

RfD

6.28E+00 *

mg/kg/d NOEL converted to mg/kg/d x 1/100
22781-23-3 Bendiocarb

NOEL

1.80E-04 *

mg/L

--

chronic NOEL whole blood cholinesterase inhibition

rat

RfD

1.70E-04 *

mg/kg/d chronic RfD
58-89-9 Lindane

NOEL

1.00E+01 *

mg/kg/d

--

acute oral NOEL --

--

RfD

1.00E-01 *

mg/kg/d acute oral NOEL x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.
e) RBC = red blood cell.

Table 99. Inhalation toxicity values - subchronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descrip-
tionb

Valuec

Units

Sourced

Additional Basis
and/or Comment

Critical Effecte

Test
Species
134-62-3 DEET

NOEL

--    

mg/kg/d

--

extrapolation inappropriate --

--

RfD

--    

-- extrapolation inappropriate
52645-53-1 Permethrin

NOEL

1.55E+01 *

mg/kg/d

--

subchronic oral NOEL --

--

RfD

1.55E-01 *

mg/kg/d subchronic oral NOEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 *

mg/kg/d

--

chronic oral NOEL --

--

RfD

7.10E-02 *

mg/kg/d chronic oral NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

3.00E-01 *

mg/kg/d

--

subchronic oral NOEL --

--

RfD

3.00E-03 *

mg/kg/d subchronic oral NOEL x 1/100
16752-77-5 Methomyl

NOEL

1.37E-01 

mg/L

EPA[432]

value for all exposure durations clinical signs of neurotoxicity/acute

rat

RfD

1.30E-01*

mg/kg/d NOEL converted to mg/kg/d x 1/300
62-73-7 Dichlorvos

NOAEL

5.00E-02   

mg/kg/d

EPA[433]

-- plasma/blood cholinesterase inhib.; 13 wk measurement in 1 year oral

dog

RfD

5.00E-04 *

mg/kg/d NOAEL x 1/100
2921-88-2 Chlorpyrifos

NOAEL

1.00E-01  

mg/kg/d

EPA[434]

-- plasma and RBC cholinesterase
inhibition

rat

RfD

1.00E-03 *

mg/kg/d NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.60E-02   

mg/kg/d

EPA[435]

-- plasma cholinesterase inhibition

rat

RfD

8.60E-05   

mg/kg/d NOAEL x 1/300
121-75-5 Malathion

LOEL

1.00E-01   

mg/L

EPA[436]

-- inhib. plasma/RBC cholinesterase;
histopathology in respiratory epithelium

rat

RfD

9.50E-02   

mg/kg/d LOEL converted to mg/kg/d x 1/300
114-26-1 Propoxur

NOEL

2.20E+00  

mg/L

EPA[437]

-- significant plasma, RBC, and cholinesterase inhibition

rabbit

RfD

6.28E+00 *

mg/kg/d NOEL converted to mg/kg/d x 1/100
22781-23-3 Bendiocarb

NOEL

1.80E-04 *

mg/L

--

chronic NOEL whole blood cholinesterase inhibition

rat

RfD

1.70E-04 *

mg/kg/d chronic RfD
58-89-9 Lindane

NOEL

1.00E+01 *

mg/kg/d

--

subchronic oral NOEL --

--

RfD

1.00E-01 *

mg/kg/d subchronic oral NOEL x 1/100
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.
e) RBC = red blood cell.

Table 100. Inhalation toxicity values - chronic exposure; noncarcinogenic effectsa

CAS No.

Active
Ingredient

Descrip-
tionb

Valuec

Units

Sourced

Additional Basis and/or Comment

Critical Effect

Test
Species

134-62-3 DEET

NOEL

--  

--

--

extrapolation inappropriate --

--

RfD

--    

-- extrapolation inappropriate
52645-53-1 Permethrin

NOAEL

5.00E+00 *

mg/kg/d

--

oral chronic NOAEL --

--

RfD

5.00E-02 *

mg/kg/d oral chronic NOAEL x 1/100
26002-80-2 d-Phenothrin

NOEL

7.10E+00 *

mg/kg/d

--

oral chronic NOEL --

--

RfD

7.10E-02 *

mg/kg/d oral chronic NOEL x 1/100
35575-96-3 Azamethiphos

NOEL

2.50E-01 *

mg/kg/d

--

oral chronic NOEL --

--

RfD

2.50E-03 *

mg/kg/d oral chronic NOEL x 1/100
16752-77-5 Methomyl

NOEL

1.37E-01   

mg/L

EPA[438]

value for all exposure durations clinical signs of neurotoxicity/acute

rat

RfD

1.30E-01 *

mg/kg/d NOEL converted to mg/kg/d x 1/300
62-73-7 Dichlorvos

NOAEL

5.00E-05   

mg/L

EPA[439]

-- blood, plasma and brain cholinesterase inhibition; 2 year inhalation study

rat

RfD

4.80E-05 *

mg/kg/d NOAEL converted to mg/kg/d x 1/300
2921-88-2 Chlorpyrifos

NOAEL

3.00E-02   

mg/kg/d

EPA[440]

-- plasma and RBC cholinesterase inhibition

dog

RfD

3.00E-04 *

mg/kg/d NOAEL x 1/100
333-41-5 Diazinon

NOAEL

2.60E-02   

mg/kg/d

EPA[441]

-- plasma cholinesterase inhibition

rat

RfD

8.60E-05   

mg/kg/d NOAEL x 1/300
121-75-5 Malathion

LOEL

1.00E-01   

mg/L

EPA[442]

-- inhib. plasma, RBC cholinesterase activity; histopathology in respiratory epithelium

rat

RfD

9.50E-02   

mg/kg/d LOEL converted to mg/kg/d x 1/300
114-26-1 Propoxur

NOEL

2.20E+00  

mg/L

EPA[443]

-- significant plasma, RBC, and cholinesterase inhibition

rabbit

RfD

6.28E+00 *

mg/kg/d NOEL x 1/100
22781-23-3 Bendiocarb

NOEL

1.80E-04    

mg/L

EPA[444]

-- whole blood cholinesterase inhibition

rat

RfD

1.70E-04    

mg/kg/d NOEL converted to mg/kg/d x 1/300
58-89-9 Lindane

NOEL

--   

--

--

no chronic exposure --

--

RfD

--   

-- no chronic exposure
a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) NOEL = no-observed-effect level, NOAEL = no-observed-adverse-effect level, LOEL = lowest-observed-effect level, RfD = reference dose.
c) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
d) "O" = other.
e) RBC = red blood cell.

Table 101. Oral slope factors; carcinogenic effectsa

CAS No.

Active
Ingredient

Group

Valueb
(mg/kg/d)-1

Sourcec

Additional Basis and/or Comment

Target Organ (Tumor Type)

Test Species

134-62-3 DEET

D

--

EPA[445]

-- not classifiable as to human carcinogenicity

rats/mice

52645-53-1 Permethrin

--

1.60E-02

O[446]

-- lung and liver adenocarcinomas

mice

26002-80-2 d-Phenothrin

--

--

--

data unavailable --

--

35575-96-3 Azamethiphos

--

--

O[447]

-- evidence of noncarcinogenicity

rats/mice

16752-77-5 Methomyl

E

--

EPA[448]

-- not likely carcinogenic to humans

not specified

62-73-7 Dichlorvos

--

--

EPA[449]

no quantitative assessment of cancer risk is required suggestive carcinogen

--

2921-88-2 Chlorpyrifos

--

--

EPA[450]

-- no evidence

rats/mice

333-41-5 Diazinon

--

--

EPA[451]

-- not likely

rats/mice

121-75-5 Malathion

--

--

EPA[452]

previous slope factor removed suggestive carcinogen; no slope factor

--

114-26-1 Propoxur

B

3.70E-03

EPA[453]

-- bladder tumor

rat

22781-23-3 Bendiocarb

E

--

EPA[454]

-- noncarcinogenic to humans

rats/mice

58-89-9 Lindane

B2/C

1.10E+00

EPA[455]

-- liver tumors

mice

a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation
b) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
c) "O" = other

Table 102. Dermal slope factors; carcinogenic effectsa

CAS No.

Active
Ingredient

Group

Valueb
(mg/kg/d)-1

Oral
Absorption
Factorc

Sourced

Additional Basis
and/or Comment

Target Organ
(Tumor Type)

Test
Species

134-62-3 DEET

--

--

--

--

data unavailable (see oral) --

--

52645-53-1 Permethrin

--

2.30E-02

0.70

O[456]

-- lung and liver adenocarcinomas

mice

26002-80-2 d-Phenothrin

--

--

--

--

data unavailable --

--

35575-96-3 Azamethiphos

--

--

--

--

data unavailable (see oral) --

--

16752-77-5 Methomyl

--

--

--

--

data unavailable (see oral) --

--

62-73-7 Dichlorvos

--

--

--

EPA[457]

no quantitative assessment of cancer risk is required suggestive carcinogen

--

2921-88-2 Chlorpyrifos

--

--

--

EPA[458]

-- no evidence of carcinogenicity

rats/mice

333-41-5 Diazinon

--

--

--

EPA[459]

-- carcinogenic activity not likely

rats/mice

121-75-5 Malathion

--

--

--

--

data unavailable (see oral) --

--

114-26-1 Propoxur

--

3.94E-03 *

0.94

--

oral slope factor x 1/OAF --

--

22781-23-3 Bendiocarb

--

--

--

--

data unavailable (see oral) --

--

58-89-9 Lindane

B2/C

1.11E+00 *

0.99

EPA[460]

oral slope factor x 1/OAF liver tumors

mice

a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
c) Oral absorption factors (OAFs) from Table 105. Used if the dermal slope factor is derived from an oral slope factor. If so, the dermal slope factor = oral SF x 1/OAF.
d) "O" = other.

Table 103. Inhalation slope factors; carcinogenic effectsa

CAS No.

Active
Ingredient

Group

Valueb
(mg/kg/d)-1

Sourcec

Additional Basis
and/or Comment

Target Organ
(Tumor Type)

Test
Species

134-62-3 DEET

--

--

--

data unavailable (see oral) --

--

52645-53-1 Permethrin

--

1.60E-02 *

--

oral slope factor --

--

26002-80-2 d-Phenothrin

--

--

--

data unavailable --

--

35575-96-3 Azamethiphos

--

--

--

data unavailable (see oral) --

--

16752-77-5 Methomyl

--

--

--

data unavailable (see oral) --

--

62-73-7 Dichlorvos

--

--

--

data unavailable (see oral) --

--

2921-88-2 Chlorpyrifos

--

--

--

data unavailable (see oral) --

--

333-41-5 Diazinon

--

--

--

data unavailable (see oral) --

--

121-75-5 Malathion

--

--

--

data unavailable (see oral) --

--

114-26-1 Propoxur

--

3.70E-03 *

--

oral slope factor --

--

22781-23-3 Bendiocarb

--

--

EPA[461]

-- carcinogenic activity not likely

rats/mice

58-89-9 Lindane

--

1.10E+00 *

--

oral slope factor --

--

a) A dash ("--") indicates one or more of the following apply: that no entry is necessary, this item is not applicable, no data were reported, or extrapolation was not done.
b) An asterisk ("*") indicates a provisional value based on a published value as described in the source or under basis.
c) "O" = other


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