### A1

- 1 

## Appendix 1

. Pyrethroid Studies Evaluated for Endpoint Selection

Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

Allethrin; S

- Bioallethrin ( 004001 ) 44517801 Acute gavage (1%

CMC )

, 10 ml/kg 0, 5, 30, 90 rat 90 neurotoxicity including hunched posture, head and/or body twitches, tremor, abnormal gait, increased body temperature, and decreased hindlimb and forelimb grip strength in females

43343301 Acute gavage (corn oil) 10 ml/kg 0, 30, 100, 300 rat 300 reduced motor activity in both sexes

, tra nsient muscle tremors

, and death in
females

43694501 Subchronic d ietary a dmix 0, 9.3, 74, 363 (M); 0, 11.1, 88, 420 (F) rat 363 decreases in mean bodyweight and food consumption ; No indications of neuropatholog y

46582501 Subchronic d ietary a dmix 0, 5, 18.1, 144,

452 rat 452 decreases in body weight, body weight gain, and food conversion in both sexes;
No indications of neurotoxicity

Bifenthrin ( 128825 ) 44862101 Subchronic d ietary a dmix 0, 2.5, 5, 10 B

( 0, 50, 100, 200 ppm ) rat >10 L OAEL

– Not Observed

44862102 Acute gavage ( no vehicle; actual
volumes 0.063 water, 0.0084, 0.0294, and 0.063 ml/kg BW) 0, 10, 35, 75 rat 75 clinical and FOB findings and differences in motor activity , and morta lity

44862103 Acute Dietary Admix 0, 2.97, 6.0,

11.8 rat 6 .0 neuromuscular findings including tremors, changes in grip strength and landing foot

- splay

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 2 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

46750501 DNT d ietary a dmix 0, 3.6, 7.2, 9.0

pre

- lactation; 0, 8.3, 16.2, 20.7 during
lactation rat Maternal: 7.2

Offspring: 7.2 Maternal: clinical signs of neurotoxicity (tremors, clonic convulsions, and increased grooming counts) Offspring : clinical signs of neurotoxici ty (excessive grooming)

00141199 Subchronic d ietary a dmix 0, 1, 4, 8, 15 rat 8 increased incidence of tremors in both

sexes

00141200 Subchronic capsules 0, 2.2, 4.4, 8.8,

17.7 Dog 4.4 increased incidence of tremors in both

sexes

00163065 Chronic capsules 0, 0.66, 1.3, 2.7, 4.4 Dog 2.7 increased incidence of tremors in both

sexes

46750501 DNT d ietary a dmix 0, 3.6, 7.2, 9 rat Maternal: 3.6

Offs p ring: 7.2 Maternal: tremors

Offspring clinical signs of neurotoxicity including tremors, clonic convulsions, and increased grooming counts Cyfluthrin, beta

cyfluthrin ( 128831 ) 00157801 Acute gavage (PEG 400) 0, 50, 60 rat <50 non

- specific disturbed behavior, rolling, tremors, stretched gait, uncoordinated gait, and salivation

00157802 Acute gavage (2%

aqueous cremophor EL) 0.01, 0.03, 0.1, 0.3, 1, 5 rat 0.1 based on ability to maintain stat ionary
posture

00157887 Acute gavage (PEG 400) 0, 40, 80 rat 80 startled gait, slow leg movement, and
titubation

44296001 Subchronic d ietary a dmix 0, 2.02, 7.99,

26.81 rat 26.81 clinical signs, changes in FOB parameters and possibly decreased body weights, body weight gains, and food consumption

44401101 Acute gavage (1% Cremophor EL) 0, 0.5, 2, 10 rat 10 clinical signs, changes in FOB
parameters a nd decreases in motor activity

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 3 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

46054101 DNT d ietary a dmix Gestation; 0, 2.4, 11.0, and

17.8 mg/kg/day:
lactation

- 0, 5.9, 25.4, and

40.9 mg/kg/day rat Maternal:

>17.8

Offspring : 17.8 Maternal: LOAEL not established;

Offspring: decreased body weight gain and decreased brain weights in females

at termination

47033001 Subchronic d ietary a dmix 0, 3.07, 12.5

, 49.1 rat 49.1 decreased food consumpt ion, body weight and body gain

00131530 Chronic d ietary a dmix 0, 1.6, 5, 15 B
(converted
from ppm) dog 15 hind limb abnormalities such as stiff gait, incoordination, arching backs

00151358 Chronic d ietary a dmix 0, 1, 4, 16 (converted
f r om ppm) dog 16 ataxia in 2 dogs on one occasion each

41267801 Subchronic d ietary a dmix 0, 0.39, 2.36

, 13.9 dog 13.9 gait abnormalities, increased incidence of vomiting, and suggesti ve decreased body weight gain

44435401 Chronic corn oil/diet 0, 1.36, 2.43, 10.64, 15.47 dog 10.64 clinical signs, gait abnormalities, and abnormal postural r eactions in males
and females

lambda

- cyhalothrin ( 128897, 128867 ) 44861510 Acute gavage (corn oil, 1ml/100g BW) 0, 2.5, 10, 35 rat 35 clinical signs of toxicity and FOB
parameters

45689101 (43013301 through 05) Subchronic Dietary Admix 0 , 2.0, 4.6,

11.4 rat >11.4 LOAEL

- not observed

00154795 Subchronic capsules (corn oil) 0, 1, 205, 10 dog 2.5 LOAEL

- 2.5 mg/kg/d based on an

increas e in incidence of liquid feces

40027902 Chronic capsules (corn oil) 0, 0.1, 0.5, 3.5 dog 0.5 clinical signs of neurotoxicity (ga it abnormalities, convulsions)

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 4 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

46449102 DNT Dietary Admix Gestation

- 0, 1.8, 4.3, 10.0;

Lactation

- 0, 4.0, 9.4, 23.1 rat Maternal: 10;

Offspring:

NA Maternal : decreased body weight, body weight gain, and food consumption;

Offspring LOAEL/NOAEL not determined
due to lack of brain morphometric s at low and mid doses, inadequate assessments of auditory startle

resp o nse in PND 61 females and motor activity
None, data provided Pytech
Chemicals
Gmbh Inc. Acute Dietary Admix 0, 0.22, 0.85, 4.2, 8.81 rat 8.81 decreased body weight gain and

neu r otoxic effects (incoordination,
abnorma l posture, flaccid musculature)

Cypermethrin; zeta

cypermethrin; beta

cypermeth r in ( 109702,

129064 )

, 43152001 Acute Gavage (Corn Oil ) 0, 30, 100, 200 mg/kg rat 100 ataxia and related conditions

43152002 Subchronic Dietary Admix 0, 31, 77, 102 rat 77 Males

- decreased body weight gain, and increased landing foot splay:
Females

- ataxia, splayed hindlimbs, impaired gait and decreased body weight gain

46449102 DNT Dietary Admix Gestation

- 0, 1.8, 4.3, and

10.0:

Lactation

- 0, 4.0, 9.4, and

23.1 rat Maternal:

10.0

Offspring:

>10 Maternal : decreased body weight, body weight gain, and food consumption;

Offspring

- LOAEL not observed

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 5 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

46670402 DNT Dietary Admix Gestation

- 0, 0, 2.9, 7.4, or

17.3 :

Lactation

- 0, 7.1, 17.5, and

39.8 rat Maternal:

>17.3

Offspring:

17.4 Maternal : LOAEL

- Not established;

Offspring : decreased body weights and body weight gains in females, altered motor activity in males and females,
and changes in brain morphometrics

44962201 Acute Gavage (undiluted) 0, 10, 50, 250 mg/kg rat LOAEL

- 50 mg/kg based on clinical signs of toxicity and FOB findings; NOAEL

- 10 mg/kg

44962202 Subchronic Dietary Admix 0 , 5.0, 26.3,

47.2 rat 26.3 decreased motor activity increased landing foot splay, decreased body weights, body wei ght gains and food consumption in males

45657401 Acute Gavage (Corn Oil, 1 ml/kg) 0, 20, 60, 100/120 rat <20 decrea s ed motor activity and gait
abnormalities
00112909/ 42068503/

92027037 Chronic capsule (corn oil) 0, 1, 5, 15 dog 5 gastrointestinal effects (liquid stool )

00112929 /

42068502 Subchronic Dietary Admix 0, 0.13, 1.25, 12.5, 37.5 dog 37.5 clinical signs (whole body tremors, exaggerated gait, ataxia, incoordination, hyperaesthesia, licking & chewing of paws; diarrhea, anorexia) & decreased body wt

44527002 Subchronic Dietary Admix 0, 10.4, 20.7, 24.6, 37.0 dog 37.0 t remor activity in both sexes and decreased body weight and body weight

ga ins in the males and females

44536801 Chronic Dietary Admix 0, 2.9, 6.0, 20.4, 33.9 dog 20.4 mortality (1 male) and abnormal clinical signs in males (irregular gait, excessive salivation, tremors), and decreased body weights and body weight gains in
females Cyphenothrin ( 129013 ) 00155352 / 42681112) Subchronic Dietary Admix 0, 5.6, 16.8,

56.4 rat >56.4 LOAEL

- Not observed

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 6 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

42706903 Chronic capsule 0, 3, 10, 60 dog 30 clinical signs of toxicity, such as
tremors, re ddish/pale mucosa, and

emesis

42717503 Subchronic capsule 0, 1, 3, 10, 30 dog 30 clinical signs of toxicity (emesis, tremor, reddish/pale mucosa )

42706904 /

42826003 Chronic Dietary Admix 0, 4.8, 14.5,

48.2 rat >48.2 LOAEL

- Not observed

Deltamethrin ( 097805 ) 44557901 Acute Gavage (Corn Oil, 5 ml/kg) 0, 5, 15, 50 mg/kg rat 15 salivation, soiled fur, impaired mobility,
and no reaction to approach or touch

response

46814301 DNT Dietary Admix 0, 1.64, 6.78,

16.1 rat Maternal:

16.1

Offspring:

16.1 Maternal : decreased body weight, body weight gain, and food consumption

Offspring : decreased body weight and body weight gain during pre

- and post

weaning, increased incidence of vocalizations (males) during FOB handling, and decreased fixed brain weight in females

44557902 Subchronic Dietary Admix 0, 4, 14, 54 rat 54 mortality, clinical signs of toxicity, FOB findings, decreased body weights, body weig ht gains and food consumption

00098104 Subchronic capsule (PEG 200) 0, 0.1, 1, 2.5,

10 dog 2.5 CNS effects, vomiting, diarrhea, and decreased body weight gains of treated
male and female dogs

Esfenvalerate ( 109301 ) 45228301 Acute Gavage (Corn Oil, 10 ml/kg) 0, 1.75, 1.90 20, 80 rat 1.9 Tremors in females (tremors observed in males at 20 mg/kg/day)

45157501 Subchronic Dietary Admix 0, 3.22, 6.39,

20.8 rat 6.39 reduced forelimb grip strength and superf icial skin wounds in male rats

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 7 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

45202301 Subchronic Dietary Admix 0, 3, 8.9, 28.8 rat 8.9 decreased body weight and body weight gain in males and decreased motor activity in females

00151030 Subchronic Dietary Admix 0, 2.5, 7.5, 15,

25 B rat 7.5 neurologic dysfunction ("jerky leg

move ments)

40215601 Subchronic Dietary Admix 0, 3.8, 5, 6.3,

15 B rat 15 decreased body weight gains and clinical signs of neurologic dysfunction (hyperactivity and “jerky leg movements”) in both sexes

00163855 Subchronic Dietary Admix 0, 0.63, 1.3, 5 dog 7.5 (range

finding study) decreased body weights in both sexes
and ata xia in one male during week 3

41637801 Acute Gavage (Corn Oil, 5ml/kg) Esfen (5, 20, 360);

Fenvalerate (20, 80, 360) rat Esfen: 20

Fenvalerate:

80 Esfen: muscular fibrillation, saliva tion
and ataxia

Fenvalerate: muscu lar fibrillation

Fenpropathrin ( 127901 ) 00127362 Subchronic Dietary Admix 0, 0.1, 0.5, 2.5,

12.5 B rat >12.5 LOAEL

- Not observed

00127363 Subchronic Dietary Admix 0, 0.2, 1.5, 5, 15, 30 B

( 0, 3, 30, 100, 300, 600 ppm) rat 30 blood chemistry (14% decrease in
kaolin

- cephalin clotting time), increased brain and kidney weights

00127364 Subchronic Dietary Admix 0, 6.25, 12.5,

18.75 B

( 0, 250, 500,

750 ppm) Dog 12.5 t remors and decreased BWG

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 8 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

00126827 Chronic Dietary Admix 0, 0.05, 0.25, 1.25, 6.25, 25 B

( 0, 1, 5, 25, 125, 500 ppm) rat 6.25 d ecreased body weight gain

00143130 Chronic Dietary Admix 0, 2.5, 6.25,

18.75 B

( 0, 100, 250,

750 ppm) Dog 6.25 t remors and soft stool

473745605 Acute gavage, corn oil, 5 mL/kg 0, 3, 6, 15, 30 rat 30 slight tremors and clonic convulsions

47345607 Subchronic Dietary Admix 0 , 4 , 13, 38 rat 38 tremors, convulsions, impaired gait, and related FOB findings predominantly in
the females

47345609 DNT Dietary Admix Gestation

- 0, 3, 8, 19;

Lactation

- 0, 7, 16, 40 rat Maternal: 19

Offspring: 19 Maternal: tremors during lactation;

Offspring : decreased BWG during pre

weaning period and increased maximum startle response amplitude in females and decreased brain weights in
males
Fluvalinate, tau (109302) 43433901 Acute Gavage (corn oil, 10 ml/kg) 0, 10, 60, 100 rat 60 clinical signs of toxicity (decreased body weights, salivation, ruffled fur, dyspnea, muscle spasms, and sedation) and

pe ripheral nerve damage in males

44900601 Subchronic Gavage (corn oil) 0, 2, 8, 32 rat 2 clinical signs of toxicology, excessive

groom ing and bulging eyes (females)

Metofluthrin ( 109709 ) 46406728 Acute Gavage (Corn Oil, 5 ml/kg) 0, 20, 50, 100 rat 100 mortality, adverse signs (twitching, tremors, and convulsions), FOB effect s and increased motor activity

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 9 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

46406729 Subchronic Dietary Admix 0,18.3, 59.8

, 178.8 rat 178 mortality (females only), clinical signs (soft/liquid feces and scant feces in the
males and tremors and twitches in the females), decreased body weight, body weight gain, and absolute and relative food consumption

Permethrin ( 109701 43046301 Acute gavage (Corn Oil, 0/300 mg/kg

- 30 ml/kg, 10 mg/kg

- 1 ml/kg, 150 mg/kg

- 15 ml/kg) 0, 10, 150, 300 rat 300 death (1 female), tremors, staggered gait, gait impairment, splayed hindlimbs, de creased forelimb grip strength

45657401 Acute g avage ( c orn

o il, 1 ml/kg) 0, 25, 75, 150 rat 75 several neurotoxi city parameters
affected

40766807 Subchronic d ietary a dmix 0, 100, 200,

400 rat 200 tremors and irritability

42933701 Subchronic d ietary a dmix 0, 15.5, 91.5,

150.3 rat 91.5 t remors, staggered and/or impaired gait, splayed hindlimbs, increased landing foot splay, abnormal posture and decreased grip strength, decreased body we ight

00129600 Chronic capsule (corn oil) 0, 5, 100, 1000 dog 1000 t remors, uncoor dinated gait, convulsions, excessive salivation, vomiting

00110647 Subchronic capsule 0, 5, 50, 500 dog 500 clinical signs of toxicity (tremors,

tran sient narcosis with nystagmus) Pyrethrins ( 69001 ) 42925801 Acute g avage (corn oil, 0, 40, 125, 400 pyrethrum

extract containing
57.5% pyrethrins rat 63 tremors in females

### Appendix 1. Toxicity Data for Screening Level Cumulative Risk Assessment

A1

- 10 Pyrethroid (PC Code) MRID Study Route of
Administration Doses (mg/kg) Species LOAEL * (mg/kg) Endpoints

Resmethrin, bioresmethrin, trans

bioresm e thrin ( 097801 ) 43838101 Subchronic d ietary a dmix 0, 35, 88, 180,

366 rat 88 increased absolute liver weight, increased BUN, moderate thyroid follicular cell vacuolization in females, moderate periportal to diffuse hepatocyte hypertrophy and
vacuolization

Tefluthrin ( 128912 ) 40141304 Subchronic d ietary a dmix 0, 2.5, 7.5,

17.5 B

( 0, 50, 150,

350 ppm) rat 7.5 changes in hemoglobin, cholesterol and liver weight

Tetramethrin ( 069003 ) 

### 42601501 /

43495501 Acute g avage (0.5% carboxymethylc ellulose, 20 ml/kg) 0, 500, 1000,

2000 rat >2000 LOAEL

– Not Observed

A 

### Acute studies are single dose studies; therefore exposure is mg/kg

B 

### Doses in study listed as parts per million (PPM); mg/kg/day values are approximations by author