Acute reference doses for agricultural and veterinary chemicals

Abamectin (sum of abamectin + 8,9–Z Isomer)

0.002

0.25

6 August 2018

Based on the overall NOAEL of 0.25 mg/kg bw per day for clinical signs in dogs (mydriasis) observed in the first week of treatment at 0.5 mg/kg bw per day.

A total uncertainty factor of 100 has been applied. The ARfD also applies to the 8,9–Z isomer of avermectin B_1a and 24-hydroxymethyl abamectin.

The 24-hydroxymethyl metabolite of abamectin is regarded as having no greater toxicity than the parent molecule.

Acephate

0.1

≥ 1.2

2005

Single dose study in humans. No inhibition of erythrocyte acetylcholinesterase activity was reported in either sex at any dose. No clinically significant changes were seen in vital signs or on electrocardiography, haematology, clinical chemistry, urine analysis or physical examination. The

NOAEL was 1.2 mg/kg bw per day, the highest dose tested.

The critical toxicological effect of acephate is the inhibition of acetylcholinesterase activity in the nervous system, an effect that is dependent on Cmax rather than on the area under the curve (AUC).

Data on inhibition in vitro indicate that human brain acetylcholinesterase is slightly less sensitive to inhibition by acephate than is rat brain acetylcholinesterase. Well conducted toxicokinetics studies, available for both rats and humans, show that there is no significant difference between the two species; in particular, Cmax values have the same relationship to administered dose in the two species, and acephate is rapidly absorbed and eliminated in both species.

Data for rats in vivo indicate that inhibition of brain acetylcholinesterase activity occurs at lower doses than those required for a similar level of inhibition of erythrocyte acetylcholinesterase activity.

Data for dogs and monkeys in vivo indicate that brain and erythrocyte acetylcholinesterase activities are nearly equally inhibited at any given dose, and do not show the difference seen in rats, which might thus be rat-specific.

Well-conducted single—and repeated-dose studies in humans clearly demonstrated a dose where no inhibition of blood cholinesterase activities occurred. Data from animals in vivo do not show sex differences in inhibition of acetylcholinesterase activity or clinical signs.

Since there is no interspecies extrapolation, an overall safety factor of 10 was used.

Acetamiprid

0.1

10

27 July 2001

Single-dose gavage neurotoxicity rat study; a NOAEL of 10 mg/kg bw was based on reductions in locomotor activity at the next higher dose.

Acibenzolar-S-methyl

0.01

10 [LOAEL]

23 April 2002

Developmental rat study; based on haemorrhagic discharge in dams at LOAEL of 10 mg/kg bw/d.

Afidopyropen

0.3

30

27 November 2017

Developmental rabbit studies; an overall NOAEL of 30–32 mg/kg bw/d was based on inappetence observed at the next higher dose.

ARfD for afidopyropen applies to the general population.

Aldicarb

0.001

0.01

15 December 1999

Human acute study; a NOAEL of 0.01 mg/kg bw was based on significant and dose-related RBC AChE inhibition at the next higher dose.

Ametoctradin

1 February 2012

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Amicarbazone

0.1

10

9 June 2006

Acute neurotoxicity study; a NOAEL of 10 mg/kg bw was based on clinical signs of neurotoxicity at the next higher dose.

Aminopyralid

10 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Amisulbrom

14 June 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Atrazine

5 December 2000

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Aureobasidium pullulans

21 February 2017

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Azafenidin

0.016

16

4 July 2001

Developmental rat study; a NOAEL of 16 mg/kg bw/d was based on increased incidence of resorptions (predominantly early) at the next higher dose.

ARfD for azafenidin only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Azimsulfuron

10 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Azinphos-methyl

0.075

0.75

5 December 2000

Acute human study; a NOAEL of 0.75 mg/kg bw was based on the absence of RBC ChE inhibition or clinical signs.

Azoxystrobin

21 April 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bacillus amyloliquefaciens

9 May 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Bacillus licheniformis

9 May 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Bacillus sphaericus strain 2362

9 May 2003

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Bacillus subtilis (see Bacillus amyloliquefaciens)

Bacillus thuringiensis

6 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Bacillus thuringiensis subsp. thuringiensis serotype 1 (strain MPPL 002)

28 August 2003

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Beauveria bassiana

8 August 2017

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Bentazone

21 April 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Benzovindiflupyr

0.1

10

23 July 2018

Clinical observations, (decreased locomotor activity at 1 h post-dosing and reduced forelimb grip strength in females at 1 h post-dosing).

Benzylpenicillin procaine

10 October 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bicyclopyrone

0.01

1

10 January 2017

Developmental rabbit study; a NOAEL of 1 mg/kg bw/d was based on increased incidence of urogenital malformations along with skeletal variations at the next higher dose.

ARfD for bicyclopyrone only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Bifenazate

10 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bitertanol

21 April 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bixafen

0.2

20

18 January 2016

Developmental rat study; a NOAEL of 20 mg/kg bw/d was based on reduced body weight gain in dams and foetuses at the next higher dose.

Boscalid

10 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bromide

10 October 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Bupivacaine

17 February 2017

There was insufficient information to establish an ARfD, however, based on its proposed pattern of use the dietary intake is likely to be low.

Buprofezin

0.5

50

31 October 2006

Developmental rabbit study; a NOAEL of 50 mg/kg bw/d was based on bodyweight loss at the next higher dose.

Butafenacil

19 November 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Captan

0.1

10

18 May 2007

Developmental rabbit study; a NOAEL of 10 mg/kg bw/d was based on reduced maternal body weight and increased skeletal variations in foetuses at the next higher dose.

ARfD for captan only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Carbaryl

0.01

1

13 December 2002

Subchronic neurotoxicity rat study; a NOAEL of 1 mg/kg bw/d was based on behavioural indications of autonomic neurotoxicity and reduced brain, plasma and RBC ChE activity at the next higher dose.

Carbendazim

0.05

50 [LOAEL]

15 February 2011

Special acute study in male rats; based on significant testicular and efferent ductal alterations at 50 mg/kg bw, the lowest dose tested.

The ARfD is also supported by an acute in vivo genotoxicity study, with increased frequencies of micronuclei were observed in spermatids at a LOAEL of 50 mg/kg bw.

Ceftiofur (as free acids and salts)

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cephalexin

22 November 2000

ARfD is considered to be unnecessary; therapeutic dose for adults ranges between 1–4 g/day.

Cetrimide

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Chlorantraniliprole

9 May 2008

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Chlorfenvinphos

0.02

1.9

5 December 2000

14-day mouse study; a NOAEL of 1.9 mg/kg bw/d was based on inhibition of RBC ChE activity at the next higher dose.

Chlormequat

0.07

7.5

23 June 2005

2-year dietary dog study; a NOAEL of 7.5 mg/kg bw/d was based on excessive salivation and muscle weakness observed after a single dose.

Chloropicrin

16 January 2014

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Chlorpyrifos

0.1

1

5 December 2000

Single dose human study; a NOAEL of 1 mg/kg bw/d was based on inhibition of RBC ChE activity at the next higher dose.

Cinmethylin

0.3

30

20 August 2003

Developmental rat study; a NOAEL of 30 mg/kg bw/d was based on clinical signs (excess salivation and urine stained abdominal fur) at the next higher dose.

Clethodim

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Clofentezine

31 December 2019

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Clitoria ternatea

23 November 2015

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

d-Cloprostenol

21 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cloquintocet acid

5 July 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Clothianidin

0.2

25

1 August 2003

Acute neurotoxicity mouse study; a NOAEL of 25 mg/kg bw was based on clinical signs (reduced spontaneous activity) at the next higher dose.

Codling Moth Granulosis Virus

25 November 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Cyantraniliprole

21 January 2013

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cyazofamid

6 June 2013

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cyclaniliprole

29 February 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cyflufenamid

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Cyhalofop-butyl

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

gamma-Cyhalothrin

0.005

0.5

12 August 2003

Developmental rat study; a NOAEL of 0.5 mg/kg bw/d was based on clinical signs of toxicity, reduced body weight gains and food consumption observed in dams at the next higher dose.

beta-Cypermethrin

0.05

4.7

19 March 2002

3-month feeding dog study; a NOAEL of 4.7 mg/kg bw/d was based on clinical signs (whole body tremors, head nodding, “lip-licking”, subduedness, ataxia, agitation and a high-stepping gait) at the next higher dose.

Decoquinate

4 June 2013

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Derquantel

0.01

1

27 May 2011

Acute neurotoxicity dog study; a NOAEL of 1 mg/kg bw was based on clinical signs (mydriasis, ptosis, dry eyes) at the next higher dose.

Dexamethasone

10 October 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Diazinon

0.01

0.2

20 December 2002

Acute dose human volunteer study; a NOAEL of 0.2 mg/kg bw was based on RBC ChE inhibition at the next higher dose.

2,6 dichlorobenzamide (BAM)

0.6

60

26 November 2015

Developmental rat study; a NOAEL of 60 mg/kg bw/d was based on increased incidence of skeletal defects of the vertebrae and sternebrae at the next higher dose.

ARfD for 2,6 dichlorobenzamide (BAM) applies to the general population.

2,4-dichlorophenoxyacetic acid (2,4-D)

0.8

75

12 September 2006

Acute neurotoxicity rat study; a NOAEL of 75 mg/kg bw was based on gait/coordination effects and decreased motor activity at the next higher dose.

Dichlorprop-P

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Dichlorvos

0.1

1

6 April 2004

Single oral dose human volunteer study; a NOAEL of 1 mg/kg bw was based on the absence of any reduction in RBC ChE activity at 1 mg/kg bw, the only dose tested.

Difethialone

0.0005

0.48 [LOAEL]

17 April 2007

Acute oral rat study; a LOAEL of 0.48 mg/kg bw was based on death.

Dimethenamid-P

0.25

25

12 August 03

Developmental rat study; a NOAEL of 25 mg/kg bw/d was based on signs of toxicity in the foetus (reduced bodyweight and incomplete ossification) at the next higher dose.

ARfD for dimethenamid-P only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary. Note: Dimethenamid-P, the S-isomer, and its racemic mixture have equivalent toxicity at similar dose levels.

Dimethoate

0.02

0.2

23 November 2010

Human volunteer study; a NOAEL of 0.2 mg/kg bw/d was based on ChE inhibition in whole blood at the next higher dose.

Dimethomorph

17 April 2020

ARfD considered unnecessary due to its low oral toxicity and the absence of any neurological effects or developmental toxicity after a single dose

Dinotefuran

1.25

125

10 August 2015

Developmental rabbit study; a NOAEL of 125 mg/kg bw/d was based on reduced body weight gain at the next higher dose.

Diphenylamine

21 April 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose. (JMPR–98).

Diquat

0.8

75

8 February 2018

Acute neurotoxicity rat study; a NOAEL of 75 mg/kg bw was based on clinical signs, inappetence and reduced bodyweight gain at the next higher dose.

Diuron

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Doramectin

0.02

1.5

14 October 2002

Developmental rabbit study; a NOAEL of 1.5 mg/kg bw/d was based on maternal toxicity with major malformations (cleft palate, phocomelia, syndactyly and coelosomia) observed in fetuses at 3 mg/kg bw/d and delayed ossification observed at 1.5 and 3 mg/kg bw/d.

ARfD for doramectin only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Emamectin benzoate

0.03

5

11 December 2018

Based on acute neurotoxicity in rats (tremors, irritability) at 10 mg/kg bw. Neurobehavioral effects were accompanied by serious histopathological observations of neuronal degeneration in brain and spinal cord as well as effects on sciatic nerves at 25 mg/kg bw.

JMPR 2011

Uncertainty factors applied were 10 for interspecies uncertainties, 10 for intraspecies uncertainties and 2 for severity of effect due to the serious neuropathological effects at 25 mg/kg bw.

Enterococcus faecium

4 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Epoxiconazole

0.2

20

16 April 2002

Developmental rabbit study; a NOAEL of 20 mg/kg bw/d was based on increased incidence of resorptions at the next higher dose.

ARfD for epoxiconazole only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Eprinomectin

0.2

1.5

31 January 2018

Human clinical trial; absence of any effects at the highest tested dose of 1.5 mg/kg bw.

ARfD was based on a clinical trial with ivermectin using a 'read across' approach due to the structural similarity and pharmacokinetic similarities of the two avermectin analogues.

Esfenvalerate

0.02

1.75

31 January 2018

Acute neurotoxicity rat study; a NOAEL of 1.75 mg/kg bw was based on clinical signs of neurotoxicity (tremors) at the next higher dose.

Ethametsulfuron-methyl

17 January 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Ethoxyquin

0.5

50

21 February 2000

Acute oral (capsule) dog study; a NOAEL of 50 mg/kg bw for effects on the hepatic biliary system and clinical signs at the next higher dose.

ARfD for ethoxyquin is based on JMPR evaluation (2005). The ARfD which is applicable for the general population includes three residues (MEQ, DHMEQ and DHEQ).

Ethoxysulfuron

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Ethyl formate

26 November 2003

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Etofenprox

1

100

4 December 2017

Developmental rabbit studies; an overall NOAEL of 100 mg/kg bw/d in two studies was based on reduced maternal bodyweight and food consumption immediately after dosing and an increased incidence of post-implantation loss at the next higher dose. (JMPR 2011, EFSA 2009)

ARfD for etofenprox only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Etoxazole

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fenamiphos

0.003

0.25

7 November 2005

Acute oral dog study; a NOAEL of 0.25 mg/kg bw was based on inhibition of RBC ChE activity at the next higher dose.

Fenbuconazole

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fenhexamid

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fenitrothion

0.03

0.33

5 December 2000

Acute single dose human volunteer study; a NOAEL of 0.33 mg/kg bw was based on the absence of any inhibition of plasma and RBC ChE activity at the highest tested dose.

Fenpyrazamine

0.8

80

15 February 2017

Acute neurotoxicity rat study; a NOAEL of 80 mg/kg bw was based on a reduction in motor activity and number of rearings at the next higher dose.

Fipronil

0.02

2.5

19 June 2006

Two acute oral neurotoxicity rat studies; a NOAEL of 2.5 mg/kg bw was based on reduced footsplay at the next higher dose.

This is a group ARfD value which includes fipronil, desulfinyl fipronil, fipronil sulphide and fipronil sulphone.

Flazasulfuron

26 September 2011

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flonicamid

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Florasulam

26 May 2009

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Florfenicol

4 January 2001

ARfD considered unnecessary due to its low oral toxicity after a single dose; structural analogs of florfenicol have a long history of therapeutic use without acute effects.

Florpyrauxifen-benzyl

8 August 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flubendiamide

14 December 2007

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fludioxonil

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fluensulfone

0.15

16.2

12 June 2014

2-Gen reproduction study; a NOAEL of 16.2 mg/kg bw/d based on post-natal loss of pups at the next higher dose.

ARfD for fluensulfone applies to the general population.

Flufenoxuron

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flumethrin

4 September 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flumiclorac pentyl

8 December 2004

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flumioxazin

0.03

3

12 December 2002

Developmental rat study; a NOAEL of 3 mg/kg bw/d was based on embryo/foetal developmental toxicity with increased incidences of cardiovascular abnormalities at the next higher dose.

ARfD for flumioxazin only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Flunixin meglumine

0.02

2

1 August 2002

6-week rat study; a NOAEL of 2 mg/kg bw/d was based clinical signs (reduced activity) at the next higher dose.

Fluopicolide

0.6

60

26 November 2015

Developmental rat study; a NOAEL of 60 mg/kg bw/d was based on increased incidence of skeletal defects of the vertebrae and sternebrae at the next higher dose.

ARfD for fluopicolide only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Fluopyram

0.5

50

6 July 2015

Acute neurotoxicity rat study; a NOAEL of 50 mg/kg bw/d was based on slightly lower motor and locomotor activity at the next higher dose.

Flupyradifurone

0.35

35

11 August 2015

Acute neurotoxicity rat study; a NOAEL of 35 mg/kg bw was based on increased incidences of piloerection and increased incidences of pupil dilation at the next higher dose.

Fluralaner

31 May 2018

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Flutolanil

28 August 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Fluxapyroxad

30 January 2012

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Glufosinate ammonium

28 August 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Glyphosate

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Halauxifen-methyl

17 September 2014

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Halofuginone

0.0003

0.025

16 June 2006

Developmental rabbit study; a NOAEL of 0.025 mg/kg bw/d was based on reduced body weight gain and food consumption, mortality and abortions at the next higher dose.

ARfD for halofuginone only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Hexaflumuron

31 August 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Hexythiazox

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Imazalil

0.05

5

29 January 2007

Developmental rabbit study; a NOAEL of 0.05 mg/kg bw/d was based on increased number of resorptions and a reduced number of live pups at the next higher dose.

ARfD for imazalil only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Imazapic

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Imazapyr

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Imazethapyr

2 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Indoxacarb (S-Isomer) + R-Isomer

0.1

12.5

30 May 2008

Acute neurotoxicity rat study; a NOAEL of 12.5 mg/kg bw was based on reduced bodyweight gain and food consumption at the next higher dose.

Ipconazole

18 January 2010

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Isofetamid

3

300

9 March 2017

Developmental rabbit study; a NOAEL of 300 mg/kg bw/d is based on reduced maternal bodyweight gain early in gestation at the next higher dose.

Isopyrazam

0.3

30

24 May 2016

Rat acute neurotoxicity study; a NOAEL of 30 mg/kg bw was based on clinical signs of toxicity (weak appearance and decreased activity).

Isoxaflutole

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Ivermectin

0.2

1.5

31 January 2018

Human clinical trial; absence of any effects at the highest tested dose of 1.5 mg/kg bw.

Kresoxim-methyl

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Ketoprofen

0.001

0.1

8 December 2000

Acute pharmacological rabbit study; a NOAEL of 0.1 mg/kg bw was based on inhibition of platelet aggregation at the next higher dose.

Lactobacillus acidophilus

4 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Lactobacillus brevis

4 September 2002

ARfD unnecessary. Naturally occurring organism—from naturally occurring background levels of the organism.

Lactobacillus casei

4 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Lactobacillus plantarum

4 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Lignocaine

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Lufenuron

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Maldison

1.5

15

12 April 2005

Acute oral human study; a NOAEL of 15 mg/kg bw was based on inhibition of RBC and plasma ChE activity at the higher dose.

Mandestrobin

30 March 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Mandipropamid

9 April 2010

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Mecoprop

0.5

50

17 January 2001

Developmental rat study; a NOAEL of 50 mg/kg bw/d was based on embryolethality and foetotoxicity (lower bodyweight and shorter CR length) at the next higher dose.

ARfD for mecoprop only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Mecoprop-p

0.5

50

17 January 2001

Developmental rat study; a NOAEL of 50 mg/kg bw/d was based on embryolethality and foetotoxicity (lower bodyweight and shorter CR length) at the next higher dose.

ARfD for mecoprop-p only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Mefentrifluconazole

27 November 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Melaleuca Oil

10

1000

12 August 2010

Based on an in vivo micronucleus study in mice using a default safety factor of 100

Meloxicam

0.004

0.04

4 August 2004

Human clinical trial; a pharmacological NOAEL of 0.04 mg/kg bw/d was based on increased blood pressure, pulse rate and ECG at higher doses.

Mesosulfuron-methyl

18 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Mesotrione

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Metalaxyl

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Metamitron

0.1

10

4 December 2017

Developmental rat study: a NOAEL of 10 mg/kg bw/d was based on the observation that acute CNS effects, in particular sedation and lower transient body temperature, occurred at doses in excess of 10 mg/kg bw. The only identified NOAEL of 10 mg/kg bw/d in the toxicological database was observed in a rat developmental study for reduced bodyweight gain. This NOAEL was selected as the basis of the numerical ARfD (EFSA, 2008).

ARfD for metmitron applies to the general population.

Metazachlor

15 July 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Methamidophos

0.003

0.3

30 January 2004

Acute neurotoxicity rat study; a NOAEL of 0.3 mg/kg bw was based on plasma, RBC and brain ChE inhibition at the next higher dose.

Methidathion

0.01

1

31 May 2004

Acute neurotoxicity rat study; a NOAEL of 1 mg/kg bw was based on RBC and brain ChE inhibition at the next higher dose.

Methiocarb

0.005

0.5

4 December 2017

Developmental rat study; a NOAEL of 0.5 mg/kg bw/d was based on clinical signs (muscle fasciculation’s) at the next higher dose.

ARfD for methiocarb applies to the general population.

Methomyl

0.02

0.1(H)

5 March 2007

Acute (capsule) human toxicity study; a NOAEL 0.1 mg/kg bw was based on erythrocyte ChE inhibition at the next higher dose.

Source; JMPR 2001.

Methoprene

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Methoxyfenozide

12 January 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

1-Methylcyclopropene

10 October 2003

There was insufficient information to establish an ARfD, however, based on its proposed pattern of use the dietary intake is likely to be low.

Metrafenone

13 April 2010

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Metribuzin

18 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Mevinphos

0.003

0.025

5 December 2000

28-day human volunteer study; a NOAEL of 0.025 mg/kg bw/d was based on inhibition of RBC ChE activity and clinical signs at the next higher dose.

Milbemectin

0.06

6

29 April 2005

Developmental rat study; a NOAEL of 6 mg/kg bw/d was based on reduced maternal bodyweight gain at the next higher dose.

ARfD for milbemectin only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Monepantel

31 August 2009

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Moxidectin

0.01

1

28 March 2002

28-day dietary dog study and developmental rabbit study; a NOAEL of 1 mg/kg bw/d was based on neurotoxicity at the next higher dose (in dogs); and maternal toxicity (reduced weight gain) at the next higher dose (in rabbits).

Niclosamide

20 September 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Novaluron

17 January 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Nuclear polyhedrosis virus of helicoverpa armigera occlusion bodies

17 December 2003

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Omethoate

0.003

0.25

20 October 2005

Acute neurotoxicity rat study; a NOAEL of 0.25 mg/kg bw was based on plasma ChE inhibition at the next higher dose.

O-phenylphenol (see 2-phenylphenol)

Oxathiapiprolin

30 July 2015

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Oxytetracycline

10 October.2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Paraquat

0.004

0.45

27 June 2003

1-year chronic feeding dog study; a NOAEL of 0.45 mg/kg bw/d was based on the likelihood that the observed pulmonary lesions would also occur after an acute exposure at the next higher dose.

Penflufen

0.5

50

10 October 2012

Acute neurotoxicity rat study; a NOAEL of 50 mg/kg bw was based on decreased motor and locomotor activity at the next higher dose.

Phenmedipham

13 April 2011

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

2-Phenylphenol

31 July 2003

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose. (JMPR'99).

Penthiopyrad

1

125

10 February 17

Acute oral neurotoxicity rat study; a NOAEL of 125 mg/kg bw was based on clinical signs (decreased motor activity, decreased body temp, hunched position and unsteady gait) at the next higher dose.

Pinoxaden

0.3

30

29 August 2005

Developmental toxicity rabbit study; a NOAEL of 30 mg/kg bw/d was based on early resorption, implantation loss, lower number of live births and reduced foetal weight at the next higher dose.

ARfD for pinoxaden only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Piperonyl butoxide

17 February 2020

ARfD considered unnecessary, due to its low oral toxicity and the absence of any neurological effects or developmental toxicity after a single dose.

Porcine gonadotrophins

25 June 2002

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Procymidone

0.1

12.5

10 May 2017

Developmental toxicity rat study; a NOAEL of 12.5 mg/kg bw/d was based on an increased incidence of hypospadias at the next higher dose.

ARfD for procymidone only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Profoxydim

29 November 2006

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Prohexadione-calcium

18 January 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Propamocarb

2

200

26 November 2015

Acute neurotoxicity rat study; a NOAEL of 200 mg/kg bw was based on a reduced activity 1 h after dosing at the next higher dose.

Propargite

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Propiconazole

0.3

30

30 August 2018

An ARfD of 0.3mg/kg bw was established based on a NOAEL of 30mg/kg bw per day in a developmental toxicity study in rats and a 100-fold safety factor. The NOAEL was identified on the basis of slight increases in rudimentary ribs and unossified sternebrae at 90mg/kg bw per day. This provides an adequate margin over the maternal toxicity and cleft palate seen at 300mg/kg bw per day. The NOAEL is also adequately protective against any acute local effects on the gastrointestinal tract based on the available data in dogs. Ataxia has also been noted in pregnant rats dosed at 360 mg/kg body weight/day.

Propineb

0.003

0.32

22 February 2017

Developmental rat study; a NOAEL of 0.32 mg/kg bw/d was based on skeletal variations at the next higher dose.

This group ARfD value which includes propineb and propylene thiourea (PTU) only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Propylene oxide

0.4

205

21 April 2006

Inhalation developmental toxicity rat study; a NOAEC of 300 ppm (equivalent to NOAEL of 205 mg/kg bw/d) was based on increased incidence of 7th cervical rib at the next higher dose.

ARfD for propylene oxide only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Propylene thiourea (PTU)

0.003

0.32

22 February 2017

See group ARfD for Propineb.

Propyzamide

0.13

40

[LOAEL]

11 December 2018

Based on a LOAEL of 40 mg/kg bw due to acute, reversible neurotoxicity (increased landing foot splay and decreased motor activity; without detectable neuropathology) in rats at this dose.

The total uncertainty factor applied is 3 for LOAEL to NOAEL extrapolation uncertainties, 10 for interspecies uncertainties and 10 for intraspecies uncertainties.

Proquinazid

1

100

10 February 2017

Acute neurotoxicity rat study; a NOAEL of 100 mg/kg bw was based on reduced motor activity at the next higher dose.

Prosulfocarb

0.4

40

30 July 2007

Acute neurotoxicity rat study; a NOAEL of 40 mg/kg bw was based on reduced motor activity at the next higher dose.

Prothioconazole

0.03

3

28 May 2008

Developmental rat study; a NOAEL of 3 mg/kg bw/d was based on increased incidence of 14th rib, increased resorptions and cleft palate at the next higher dose.

ARfD for prothioconazole only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary. Since the residue definition for risk assessment in all commodities is expressed as prothioconazole-desthio and this metabolite is of higher toxicity than the parent, a group ARfD was established to include prothioconazole-desthio.

Pydiflumetofen

21 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Pyraclostrobin

0.05

5

26 June 2008

Developmental rabbit study; a NOAEL of 5 mg/kg bw/d was based on early resorptions at the next higher dose.

ARfD for pyraclostrobin only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Pyraflufen-ethyl

0.2

20

17 December 2004

Developmental rabbit study; a NOAEL of 20 mg/kg bw/d was based on increased maternal mortality and morbidity at the next higher dose.

Pyrasulfotole

0.2

200 [LOAEL]

20 August 2008

Acute neurotoxicity rat study; based on decreased motor and locomotor activity at a LOAEL of 200 mg/kg bw.

Pyrethrins

0.2

20

31 July 2003

Acute neurotoxicity rat study; a NOAEL of 20 mg/kg bw was based on neurotoxicity observed at the next higher dose.

Adopted from JMPR ‘99.

Pyridalyl

29 April 2004

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Pyrimethanil

10 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Pyriofenone

26 November 2014

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Pyroxasulfone

27 June 2013

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Pyroxsulam

14 April 2008

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Quinclorac

2

200

13 September 2004

Acute oral toxicity gavage mouse study; a NOAEL of 200 mg/kg bw was based on clinical signs at the next higher dose.

Quinoxyfen

15 January 2002

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Ractopamine hydrochloride

0.001

0.13

30 July 2002

Human study; a NOAEL of 0.13 mg/kg bw was based on increased heart rate at the next higher dose.

Saccharomyces cerevisiae

4 September 2002

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Saflufenacil

0.05

5

13 February 2017

Developmental rat study; a NOAEL of 5 mg/kg bw/d was based on an increased incidence of bent scapula and wavy ribs in the absence of maternal toxicity at the next higher dose.

ARfD for salflufenacil only applies to women of child-bearing age. An ARfD for the general population is considered to be unnecessary.

Sedaxane

24 April 2011

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Spinetoram

5 May 2008

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Spinosad

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Spirotetramat

1

100

26 May 2008

Acute neurotoxicity rat study; a NOAEL of 100 mg/kg bw was based on clinical signs and decreased motor activity at the next higher dose.

Spiroxamine

0.2

20

2 July 2001

Acute neurotoxicity rat study; a NOAEL of 20 mg/kg bw was based on decrease in landing footsplay at the next higher dose.

Streptomyces lydicus

7 June 2016

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Sulfoxaflor

0.25

25

27 June 2013

Acute oral neurotoxicity rat study; a NOAEL of 25 mg/kg bw was based on decreased motor activity at the next higher dose.

Sulfuryl Fluoride

0.3

31

24 August 2006

Acute inhalational neurotoxicity rat study; a NOAEL of 31 mg/kg bw (300 ppm) was based on the absence of any observed effects at the highest tested concentration of 300 ppm.

Tebuconazole

0.3

30

11 December 2018

Based on a maternal and developmental toxicity NOAEL of 30 mg/kg bw/day in rats and rabbits. Maternotoxicity manifested as decreased body weight gain. Visceral and skeletal developmental anomalies occurred at higher doses. This is supported by a NOAEL of 30 mg/kg bw/day in the 28-day oral (gavage) toxicity study in rats based on changes in haematological parameters detected at the next highest dose. The haematological changes could potentially be caused by a single dose.

Total uncertainty factor applied was 100.

Tepraloxydim

13 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Terbuthylazine

4 May 2001

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Tetraconazole

0.2

16

12 December 2002

4-week dietary rat study; a NOAEL of 16 mg/kg bw/d was based on clinical signs at the next higher dose.

Thiacloprid

0.03

3.1

20 July 2001

Acute oral neurotoxicity rat study; a NOAEL of 3.1 mg/kg bw was based on reduced motor & locomotor activity at the next higher dose.

Thiram

0.1

10

2 July 2010

Acute neurotoxicity rat study; a NOAEL of 10 mg/kg bw was based on reduced locomotor activity at the next higher dose.

Tilmicosin

0.4

36

29 August 2002

7-day oral dosing (capsule) dog study; a NOAEL of 10 mg/kg bw/d was based on the absence of clinical signs (ataxia, dyspnoea, bilateral mydriasis) during the first 4 days of dosing.

Tolfenamic acid

0.005

[0.5]

16 January 2001

Lowest effective therapeutic dose (as a single dose) for treatment of pyresis in children.

Topramezone

16 June 2016

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Trifloxystrobin

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Trifloxysulfuron

13 February 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Trinexapac-ethyl

10 May 2017

ARfD considered to be unnecessary due to its low oral toxicity and the absence of any developmental toxicity after a single dose.

Tulathromycin

0.1

100

16 August 2006

Acute tolerance dog study; a LOAEL of 100 mg/kg bw was based on the occurrence of emesis and loose stools.

Ulocladium oudemansii

12 December 2003

ARfD unnecessary. Naturally occurring organism—residues from its use are unlikely to be distinguishable from naturally occurring background levels of the organism.

Zilpaterol

0.00004

0.00076[LOAEL]

24 October 2016

Single dose human study; a LOAEL of 0.05 mg/person (equal to 0.00076 mg/kg bw) was based on the observation of tremors at the lowest tested dose.