Chlorpyrifos

Endpoint summary

Description of key information

Duration/Value Type	Species	Value	Guideline	Reliability
Oral LD50	Rat, female	200 mg/kg	OECD 423, EPA OPPTS 870.1100	1
Oral LD50	Rat, male/female	223 mg/kg	OECD 401, EPA OPP 81-1	1
Oral LD50	Rat, male/female	>66 mg/kg	OECD 401	2
Oral LD50	Rat, male/female	163 mg/kg (M); 135 mg/kg (F)	no guideline	2
Oral LD50	Mouse, female	300 mg/kg	OECD 423, EPA OPPTS 870.1100	1
Oral LD50	Mouse, female	>69 mg/kg	no guideline	2

Duration/Value Type	Species	Value	Guideline	Reliability
Inhalation 6 -hr LC50	Rat, male/female	14 ppb	EPA OPP 81-3	1
Inhalation 4 -hr LC50	Rat, male/female	>200 mg/m3 (14 ppb)	no guideline	1

Duration/Value Type	Species	Value	Guideline	Reliability
Dermal LD50	Rabbit	> 5000 mg/kg	OECD 402, OPPTS 870.1200, EU Method B.3	1
Dermal LD50	Rat	> 2000 mg/kg	EPA 81-2	1
Dermal LD50	Rat	> 2000 mg/kg	no guideline	1

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Acute Oral Toxicity 2-1-1

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Substance ID: TSN308540
Batch #: 2K04161692
Purity: 98.0%

Species:

rat

Strain:

Wistar

Remarks:

RCCHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 183.1 to 215.5 g
- Fasting period before study: Yes, overnight
- Housing: Three rats/cage (Solid bottomed, polypropylene rat cages covered with stainless steel grid tops were used)
- Diet: ad libitum (with the exception of overnight fasting prior to dosing and three hours post-dosing)
- Water: ad libitum
- Acclimation period: 6 to 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 23 °C
- Humidity: 65 to 67%
- Air changes: Minimum 15/hour
- Photoperiod: 12 hrs dark/ 12 hrs light

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test item was solid so it was mixed in corn oil and the dose concentration (200, 30 and 5 mg/mL) was adjusted according to the body weight to permit constant dose volume (10 mL/kg body weight). Individual dose volume was adjusted according to body weight. All rats were dosed by gavage (day 0) using a metal cannula attached to a 1 mL disposable syringe which was graduated up to 1 mL.

Doses:

Set I: 2000 mg/kg
Set II: 300 mg/kg
Set III & IV: 50 mg/kg

No. of animals per sex per dose:

3 females per set

Control animals:

no

Details on study design:

- Duration of observation period following administration: The rats from set I, II, III and set IV were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, the rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing.
- Frequency of observations and weighing: Individual body weight was recorded prior to dosing on day 0 and after dosing, on days 7 and 14 and at death.
- Necropsy of survivors performed: Yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

All animals treated with 2000 and 300 mg/kg body weight were found dead. No mortality was observed in rats with 50 mg/kg body weight.

Clinical signs:

other: Clinical signs like lethargy, tremors, abdominal breathing and chromodacryorrhea were observed in rats at dose levels of 2000 and 300 mg/kg body weight. No signs of toxicity were observed in rats at the dose level of 50 mg/kg body weight.

Gross pathology:

External: External examination did not reveal any abnormality of pathological significance in any animal treated at 2000, 300 and 50 mg/kg body weight.
Internal: Visceral examination of animals found dead revealed liver congestion (Animal N° 1, 2, 3, 4, 5 and 6) and lung congestion (Animal N° 2, 3 and 5) respectively whereas the terminally sacrificed animals did not reveal any lesion. Lesions observed in the rats found dead could be correlated with the test item used in the present study.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Oral LD50 (Female Rat): 200 mg/Kg body weight

Executive summary:

The acute oral toxicity study was performed according to the acute toxic class method (OECD 423, OCSPP 870.1100, EC B.1 and JMAFF 2-1-1). The test substance was administered to fasted Wistar rats at dose levels of 2000 (for set I), 300 (for set II) and 50 (III and IV) mg/kg body weight. Observations included daily clinical signs and weekly body weight recordings over a 14 day observation period. Necropsy examination was performed in all animals.

Rats from set I and II were given a single dose of 2000 and 300 mg/kg body weight, respectively. Clinical signs like lethargy, tremors, abdominal breathing and chromodacryorrhea were observed after dosing and all animals were found dead. Visceral examination revealed congestion of the liver and lungs with no external abnormalities.

Hence, another two sets (set III and IV) of fasted Wistar rats (3 females per set) were given a single oral dose of the test substance at 50 mg/kg body weight.

No signs of toxicity, including clinical signs and body weight, were observed in any rat treated at the dose level of 50 mg/kg body weight during the whole observation period.

External and visceral examination of the terminally sacrificed rats did not reveal any lesion of pathological significance.

The acute oral median lethal dose (LD50 cut-off value) of the test substance in Wistar rats was found to be 200 mg/kg body weight.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF Acute Oral Toxicity

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Substance ID: TSN100759
Lot #: 7299412
Purity: 97.6%

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methocellulose

Doses:

50, 100 or 500 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

223 mg/kg bw

Based on:

test mat.

Mortality:

All rats given 500 mg/kg died by test day 3. All rats given 50 or 100 mg/kg survived the two-week observation period.

Clinical signs:

other: Clinical observations in rats from all dose levels consisted of salivation and/or lacrimation, and perineal soiling with feces and/or urine. In addition, most female rats given 500 mg/kg had decreased activity and were laterally recumbent before death. Al

Gross pathology:

There were no treatment-related gross pathologic observations in any of the rats.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Oral LD50 (Rat): 223 mg/kg body weight

Executive summary:

The test substance was evaluated for acute oral toxicity according to the guidelines OECD 401. Five male and five female Fischer 344 rats per dose level received 50, 100 or 500 mg/kg of the test substance in 0.5% methocellulose by single-dose oral gavage.

Parameters evaluated during the two-week observation period included body weights and in-life observations. All animals were examined for gross pathological changes.

All rats given 500 mg/ kg died by test day 3. All rats given 50 or 100 mg/kg survived the two-week observation period.

Clinical observations in rats from all dose levels consisted of salivation and/ or lacrimation, and perineal soiling with feces and/ or urine. In addition, most female rats given 500 mg/kg had decreased activity and were laterally recumbent before death. All animals given 50 or 100 mg/kg appeared normal by test day 6. There were no treatment-related gross pathologic observations.

Under the conditions of this study, the acute oral LD50 of the test substance for male and female Fischer 344 rats was 223 mg/kg, by linear interpolation.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 2-1-1

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

TSN100759
Lot: 7299412
Purity: 97.6%

Species:

mouse

Strain:

other: Swiss albino

Sex:

female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

300 (for set I) mg/kg body weight and 50 (for set II and III) mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Based on:

test mat.

Mortality:

Two out of three female mice treated with 300 mg chlorpyrifos TGAI/kg body weight was found dead on day 3 post-dosing. No mortalities were observed at 50 mg/kg body weight.

Clinical signs:

other: Treatment-related clinical signs like lethargy, tremors and abdominal breathing were observed in mice treated with 300 mg chlorpyrifos TGAI/kg body weight while no sign of toxicity was observed in mice treated with 50 mg chlorpyrifos TGAI/kg body weight.

Gross pathology:

External examination of found dead and terminally sacrificed female mice did not reveal any abnormality of pathological significance. Visceral examination of the early decedent mice treated at 300 mg/kg body weight revealed congestion of liver (mouse N° 2 and 3). No lesions of pathological significance were recorded in terminally sacrificed mice treated at 300 and 50 mg/kg body weight.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 (female mice) = 300 mg/kg

Executive summary:

The acute oral toxicity study was performed according to the acute toxic class method. The test item chlorpyrifos TGAI mixed in corn oil was administered to fasted Swiss albino miceat a dose of 300 (for set I) mg/kg body weight and 50 (for set II and III) mg/kg body weight. Observations included daily clinical signs and weekly body weight recordings over a 14 day observation period. Necropsy examination was performed in all animals.

Initially one set of female mice was given a single dose of 300 mg/kg body weight. Mice showed lethargy, tremors and abdominal breathing and two out of three mice were found dead on day 3. Visceral examination revealed congestion of liver (mice N° 2 and 3) with no external abnormalities. Hence, another two sets (set II and III) of fastedSwiss albino mice(3 females per set) were given a single oral dose ofchlorpyrifos TGAIat 50 mg/kg body weight. No signs of toxicity, including clinical signs and body weight recording, were observed in any mice treated at the dose level of 50 mg/kg body weight during the whole observation period. External and internal examination of terminally sacrificed mice did not reveal any lesion of pathological significance.

The acute oral median lethal dose (LD₅₀cut-off value) ofchlorpyrifos TGAIinSwiss albino micewas found to be 300 mg/kg body weight. Based on the results of this study, an indication of the classification forchlorpyrifos TGAIisas follows:

Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2011): Category 3

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Groups of five female Crl:CD1(ICR) mice were fed diets formulated to provide 1000, 1500, or 2000 ppm chlorpyrifos for targeted doses of approximately 150, 225, or 300 mg test material/kg body weight (mg/kg bw), for one 24-hour exposure. The mice were fed control feed for the remainder of the 14-day observation period. Study parameters included cage-side clinical observations, detailed clinical observations (DCO), body weights, feed consumption, and gross necropsy.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Lot # KC28161419, TSN101285
Purity: 99.8%

Species:

mouse

Strain:

other: Crl:CD1(ICR)

Sex:

female

Route of administration:

oral: feed

Vehicle:

acetone

Doses:

1000, 1500, 2000 ppm (corresponding to 150, 225, and 300 mg/kg, respectively)

No. of animals per sex per dose:

5

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 69 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived and appeared normal throughout the 14-day observation period.

Clinical signs:

other: All animals appeared normal throughout the 14-day observation period.

Gross pathology:

There were no gross pathological findings at study termination.

Other findings:

Feed consumption on test day 1 was reduced by 62.5 %, 71.0%, and 73.3% in the 1000, 1500, and 2000 ppm dose groups, respectively, when compared to the pre-treatment values (day –1 to 1). Scratched feed from any animals during the 24- hour treatment period was collected and measured to obtain the most accurate feed consumption value.

The actual concentrations of test material in the diet ranged from 91.1% to 99.1% of targeted values. The overall relative standard deviations (RSDs) for the low and high dose were 2.8% and 7.2%, respectively; therefore, the diets containing

Chlorpyrifos were homogeneous.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

LD50 (female mice) > 69 mg/kg

Executive summary:

Groups of five female Crl:CD1(ICR) mice were fed diets formulated to provide 1000, 1500, or 2000 ppm chlorpyrifos for targeted doses of approximately 150, 225, or 300 mg test material/kg body weight (mg/kg bw), for one 24-hour exposure. The mice were fed control feed for the remainder of the 14-day observation period. Study parameters included cage-side clinical observations, detailed clinical observations (DCO), body weights, feed consumption, and gross necropsy.

 

All animals survived and appeared normal throughout the 14-day observation period. Feed consumption on test day 1 was reduced by 62.5 %, 71.0%, and 73.3% in the 1000, 1500, and 2000 ppm dose groups, respectively, when compared to the pretreatment values (day -1 to 1). The 24-hour test material intake calculated values were 51, 57, and 69 mg/kg bw for the 1000, 1500, and 2000 ppm groups, respectively. These values are lower than the expected target values due to the decreased feed consumption in all animals.

 

Under the conditions of this study, the acute oral LD50 was greater than 69 mg/kg bw in female Crl:CD1(ICR) mice during a single 24-hour dietary exposure. 

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

Animals were fed a single dose by intubation. All animals were weighed and observed at intervals over a 2-week post feeding period. Pathological observation is made on representative animals.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

other: Rat, Rabbit, Cavy and Chick

Strain:

not specified

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

Rat: 5% solution in corn oil
Rabbit: 5% solution in corn oil
Cavy: 10% solution in corn oil
Chick: Undiluted

No. of animals per sex per dose:

Rat: 5 per sex per dose
Rabbit: 2 per dose
Cavy: 4 per dose
Chick: 4 per dose

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

0.135 other: g/Kg

Based on:

test mat.

Remarks on result:

other: Rat

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.163 other: g/Kg

Based on:

test mat.

Remarks on result:

other: Rat

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 1 - <= 2 other: g/Kg

Based on:

test mat.

Remarks on result:

other: Rabbit

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.504 other: g/Kg

Based on:

test mat.

Remarks on result:

other: Cavy

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.032 other: g/Kg

Based on:

test mat.

Remarks on result:

other: Chick

Conclusions:

LD50 (Rat, male): 0.163 g/Kg
LD50 (Rat, female): 0.135 g/Kg
LD50 (Rabbit): 1-2 g/Kg
LD50 (Cavy, male): 0.504 g/Kg
LD50 (Chick, male): 0.032 g/Kg

Executive summary:

Animals (Rat, rabbit, Cavy and Chick) were fed a single dose by intubation. All animals were weighed and observed at intervals over a 2-week post feeding period. Pathological observation is made on representative animals. The summary of acute oral toxicity is as follows:

LD50 (Rat, male): 0.163 g/Kg

LD50 (Rat, female): 0.135 g/Kg

LD50 (Rabbit): 1-2 g/Kg

LD50 (Cavy, male): 0.504 g/Kg

LD50 (Chick, male): 0.032 g/Kg

 

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

2 samples of Chlorpyrifos samples were tested:

Sample 1: Dursban Technical
Batch: EK 830516110.
Purity: Not reported

Sample 2: Dursban F (OP 1)
Batch: 830516110.
Purity: Not Reported

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl: CD(SD) BR

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: polyethylene glycol for Dursban F and corn oil for Dursban F (OP1)

Doses:

Dursban F: 25, 50, 71, 100, 141, 200 mg/kg
Dursban F (OP1): 180, 255, 360, 500 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Screening studies were conducted (1 rat/gender/dose) to help set dose levels for the definitive studies.

Definitive studies were conducted on fasted animals. All animals were observed for overt signs of toxicity or behavioural change at 1 and 4 hours after treatment and subsequently once daily for 14 days. All gross, visible toxic or pharmacological effects were recorded. Individual body weights were recorded on the day before treatment (day -1), on the day of treatment, 7 and 14 days after treatment, and at death. All animals were subjected to a gross necropsy examination. No tissues were retained. Animals surviving the 14 day observation period were killed by exposure to high levels of carbon dioxide.

Preliminary study:

Dursban F: The mortalities indicated an oral" median lethal dose between 100 and 200 mg/kg.
Dursban F (OP1): The mortalities indicated an oral median lethal dose between 100 and 500 mg/kg.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

74 mg/kg bw

Based on:

test mat.

95% CL:

59 - 89

Remarks on result:

other: Dursban F

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

84 mg/kg bw

Based on:

test mat.

95% CL:

56 - 117

Remarks on result:

other: Dursban F

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

66 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Dursban F

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

229 mg/kg bw

Based on:

test mat.

95% CL:

156 - 282

Remarks on result:

other: Dursban F (OP1)

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

287 mg/kg bw

Based on:

test mat.

95% CL:

201 - 394

Remarks on result:

other: Dursban F (OP1)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

181 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Dusban F (OP1)

Mortality:

Dursban F: One animal treated with 71 mg/kg was found dead 1 hour after treatment. Two animals from each dose group treated with 141 and 200 mg/kg were found dead 4 hours after treatment. The majority of animals were found dead 2 days after treatment. Death continued to be noted up to 5 days after treatment.

Dursban F (OP1): A total of 27 animals (11 male. 16 female) died or were killed during the study period. Four animals treated with 500 mg/kg and 5 animals treated with 360 mg/kg had to be killed on day 1 for humane reasons. In addition two animals receiving 500 mg/kg. 3 animals receiving 360 mg/kg. 2 animals receiving 255 mg/kg and 3 animals receiving 160 mg/kg were killed for humane reasons between days 2 and 4. Deaths continued to be noted on days 2 and 3.

Clinical signs:

other: see "other information" section

Gross pathology:

Dursban F: Pathological findings occasionally noted in animals necropsied at termination were associated with the lungs and liver. The majority of animals necropsied at termination were unremarkable. Necropsy of animals dying during the study showed abnormal appearance of the liver and lungs. A common finding in these animals was yellow/blacK discolouration of the G.I. tract and stomach. The G.I. tract and stomach also appeared haemorrhagic.

Dursban F (OP1): All animals necropsied at termination were unremarkable. Necropsy of animals dying or being killed during the study showed abnormal appearance of the kidneys, liver and lungs. Common finding in these animals were haemorrhagic appearance of the stomach and a coloured fluid in the G.I. tract.

Dursban F: Common signs of toxicity noted in animals treated with 200 mg/kg on the day of dosing were lethargy or prostration. hunched posture. piloerection and salivation. Occasional

signs of tremor were also noted during this period. These signs continued to be noted in surviving animals on day 1 at which time shallow breathing, protruding and watering eyes

were also noted. There were no survivors on day 2.

Similar signs of toxicity were also noted in animals treated with 141 mg/kg during the day of dosing and on days 1 and 2. The surviving male appeared normal on day 3. All animals treated with 100 mg/kg were lethargic or prostrate with hunched posture and piloerection on the day of

dosing. One animal was noted as having tremors 1 hour after dosing, however, this sign was not recorded later in the day. The above signs persisted to day 4 with shallow breathing (day 1 only) and semi closed eyes (days 2 - 4) being noted also. All surviving animals appeared normal from day 5. All surviving animals treated with 71 mg/kg were lethargic or prostrate with hunched posture, piloerection and tremors during the day of dosing. These signs persisted to day 2 with occasional signs of chromodacryorrhoea and shallow breathing being noted between days 1 and

3.

 

Common signs of toxicity noted in animals treated with 50 mg/kg were lethargy or prostration with hunched posture, piloerection, tremors and exophthalmia during the day of dosing. Other signs of abnormal gait and general staining of the fur were noted. All animals were normal on day 3. Signs of lethargy were noted in animals treated with 25 on the day of dosing and up to 2 days after treatment. animals were normal on day 3.

 

Dursban F (OP I): Common signs of toxicity noted in animals treated with 500 mg/kg on the day of dosing were lethargy, hunched posture, piloerection, tremor, chromodacryorrhoea and salivation. These signs continued to be noted, in surviving animals, at times from day 1 to day 9. Occasional signs of prostration, ataxia, general staining and sensitivity to stimuli were also noted during this period. Nine animals died or were killed between day 1 and day 4. The surviving male appeared normal from day 10.

 

Common signs of toxicity noted in animals treated with 360 mg/kg on the day of dosing were lethargy. Hunched posture. piloerection. tremor and salivation. These signs continued to be noted on day 1 and day 2 at which time prostration and a stained body were also noted. There were

no survivors on day 2. Signs of toxicity noted in animals treated with 255 mg/kg on the day of dosing were lethargy. piloerection, tremor, chromodacryorrhoea. sensitivity to stimuli and salivation. These signs continued to be noted in surviving animals at times from day 1 to day 7. Signs of prostration, hunched posture. ataxia and general staining were also noted occasionally during this period. Three animals died and 2 were killed. for humane reasons, on day 2. All surviving animals appeared normal from day 8.

 

Signs of toxicity noted in animals treated with 180 mg/kg on the day of dosing were lethargy. hunched posture. piloerection. chromodacryorrhoea and ataxia. These signs. and also tremor, convulsions and a stained body were noted. in surviving animals, at times from day 1 to day 6. Three animals were killed, for humane reasons. on day 2. All surviving animals appeared normal from day 7.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Dursban F (male/female) LD50: 74 mg/kg
Dursban F (OP1): (male/female) LD50: 229 mg/kg

Executive summary:

Two samples of the test substance were evaluated for acute oral toxicity according to the guidelines OECD 401. Five male and five female Crl: CD(SD) BR rats per dose level received 25, 50, 71, 100, 141, 200 mg/kg (Dursban F) or 180, 255, 360, 500 mg/kg (Dursban F (OP1)) by single-dose oral gavage. Parameters evaluated during the two-week observation period included body weights and in-life observations. All animals were examined for gross pathological changes.

 

For Dursban F, the LD50 (all animals) was 74 mg/kg (59 - 89), (males) 84 mg/kg (56 - 117), and (females) 66 mg/kg (95% fiducial limits cannot be calculated).  For Dursban F (OPl), the LD50 (all animals) was 229 mg/kg (156-282), (males) 287 mg/kg (201 - 394), and (females) 181 mg/kg (95% fiducial limits cannot be calculated).

Reference 7

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

GLP compliance:

no

Test type:

other: Not specified

Species:

rat

Strain:

Sherman

Remarks:

Crl: CD(SD) BR

Sex:

male/female

Route of administration:

oral: unspecified

No. of animals per sex per dose:

60 Males & 70 Females

Control animals:

not specified

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

155 mg/kg bw

Based on:

test mat.

95% CL:

>= 132 - <= 181

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

82 mg/kg bw

Based on:

test mat.

95% CL:

>= 69 - <= 97

Conclusions:

LD50 (Rat, male): 155 mg/kg
LD50 (Rat, female): 82 mg/kg

Executive summary:

LD50 values have been determined for the test substance in a single dose by the oral route to Sherman strain adult rats.

LD50 (Rat, male): 155 mg/kg

LD50 (Rat, female): 82 mg/kg

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Quality of whole database:

Seven acute oral toxicity studies were conducted on rat and mouse. Rat study tested in according to OECD guideline 423 and EPA OPPTS 870.1100 is considered as key study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline followed

Principles of method if other than guideline:

5 male and 5 female rats were exposed for 4-hours by inhalation to the vapour obtained by passing air through the molten test substance at the concentration of 0.2 g/m3. Control group was also included in the study. The animals were observed for 14 days.

GLP compliance:

yes

Limit test:

no

Specific details on test material used for the study:

Lot # EK 830616110
Purity: Not reported

Species:

rat

Strain:

other: albino rats (HC/CFHB)

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Duration of exposure:

4 h

Concentrations:

0.2 g/m3

No. of animals per sex per dose:

5

Control animals:

yes

Key result

Sex:

male/female

Exp. duration:

4 h

Remarks on result:

other: The acute hazard associated with exposure to the vapour of the test substance is likely to be low

Mortality:

No deaths

Clinical signs:

other: During exposure, closing or partial closing of the eyes, excessive salivation, abnormal body posture, abnormal respiratory pattern and discharge from the snout. These signs were considered to be consistent with the response to a mildly irritant vapour.

Body weight:

Some rats showed a slight loss in body weight for 1 day following exposure to vapour from the test substance. Subsequently the rate of body weight gain was similar to that for the control rats.

Gross pathology:

No test substance related findings

Conclusions:

The acute hazard associated with exposure to the vapour of the test substance is likely to be low

Executive summary:

5 male and 5 female rats were exposed for 4-hours by inhalation to the vapour obtained by passing air through the molten test substance at the concentration of 0.2 g/m3. Control group was also included in the study. The animals were observed for 14 days.

There were no deaths. During exposure, closing or partial closing of the eyes, excessive salivation, abnormal body posture, abnormal respiratory pattern and discharge from the snout. These signs were considered to be consistent with the response to a mildly irritant vapour. During the observation period, all exposed rats were normal in appearance and behaviour. Some rats showed a slight loss in body weight for 1 day following exposure to vapour from the test substance. Subsequently the rate of body weight gain was similar to that for the control rats.

Food and water consumption were not affected by exposure to vapour from the test substance. No gross findings considered to be related to treatment were observed.

The acute hazard associated with exposure to the vapour of the test substance is likely to be low.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Purity: 99.7%

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, New York
- Age at study initiation: 7 to 10 weeks
- Fasting period before study: No
- Housing: Rats were housed individually in stainless steel wire cages
- Diet: ad libitum (except during exposure)
- Water: ad libitum (except during exposure)
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 22-24°C
- Humidity: 34-40%
- Photoperiod: 12 hrs dark/12 hrs light

Route of administration:

inhalation: vapour

Type of inhalation exposure:

other: whole-body and nose-only exposures

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel and glass one cubic meter Rochester-type chambers for whole body exposure; ADG nose-only exposure system for nose-only exposure
- Method of holding animals in test chamber: Animals were individually housed for whole body exposure
- Source and rate of air: Airflow through each pipe was maintained at approximately 68 L/min or 40 L/min and 35°C. For whole-body exposures, chamber airflow was maintained at 200 L/min. For nose-only exposures, chamber airflow was maintained at 30 L/min.
- Temperature in air chamber: 22-24°C
- Humidity in air chamber: 34-40%

TEST ATMOSPHERE
- Brief description of analytical method used: Nominal concentrations could not be determined due to the small amount of test substance (less than 10 mg/day) vaporized from the large pipe containing glass beads and the test substance.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

6 h

Concentrations:

First whole-body exposure: 0 (control) and 6 ppb
Second whole-body exposure: 0 (control) and 3.5 ppb
Nose-only exposure: 0 (control) and 14 ppb

No. of animals per sex per dose:

First whole-body exposure: 12/sex
Second whole-body exposure: 6/sex
Nose-only exposure: 6/sex

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: All rats were weighed and observed prior to exposure. Clinical observations of all animals were routinely made at least once daily during a two-week post-exposure period. All rats exposed to 6 ppb (whole-body) were weighed on test days 1, 2, 8, 11, and 15. Rats exposed in the nose-only chamber were weighed on test days 1, 2, 4, 8, 11 and 15. Animals exposed to 3.5 ppb (whole-body) were weighed prior to exposure and sacrificed immediately after exposure. Evaluation of 3.5 ppb whole-body exposed rats was limited to past-exposure plasma cholinesterase activity determinations and grass pathology because a plasma cholinesterase activity decrease was the only effect that had been observed in 6 ppb whole-body exposed rats.
- Necropsy of survivors performed: yes

Statistics:

Body weights and plasma cholinesterase activity were evaluated by Bartlett's test for equality of variances. Based on the outcome of Bartlett's test, exploratory data analysis was performed by a parametric or non-parametric analysis of variance (ANOVA), followed by Dunnett's test or Wilcoxon Rank-Sum test with a Bonferroni correction for multiple comparisons. Statistical outliers were identified by a sequential test, but were not routinely excluded.

Key result

Sex:

male/female

Exp. duration:

6 h

Remarks on result:

other: the test substance does not appear to have a significant acute vapor inhalation exposure hazard

Mortality:

One male exposed to 6 ppb was lethargic on test day 8, with urine staining and porphyrin-like staining around the muzzle. This rat was found dead on day 9. Necropsy revealed blood in the abdominal cavity, therefore the probable cause of death was physical trauma.

Clinical signs:

other: During exposure, all rats that were visible appeared normal. One female exposed to 14 ppb experienced trauma to the left eye, apparently in the restrainer during nose-only exposure. Observations of hyperactivity were made on two female rats two days after

Body weight:

There were no exposure-related effects on body weights.

Gross pathology:

There were no exposure-related gross changes observed in any whole body exposed (3.5 or 6 ppb) or nose-only exposed (14 ppb) male or female rats. One male rat exposed to 6 ppb that died early had gross lesions suggestive of abdominal trauma; this was not attributable to the test substance exposure. All other gross observations were considered to be incidental findings.

Other findings:

The mean plasma cholinesterase activity of male and female rats was decreased by 13% and 24%, respectively, following whole-body exposure to 6 ppb. There were no detectable effects on plasma cholinesterase activity after a 2-week recovery period and no detectable effects in 3.5 ppb (whole-body) or 14 ppb (nose-only) exposed rats.

Conclusions:

The test substance does not appear to have a significant acute vapor inhalation exposure hazard.

Executive summary:

Fischer 344 rats were exposed to the test substance (according to the guideline EPA OPP 81-3) vapor for 6 hours by whole-body (3.5 or 6 ppb) or nose-only (14 ppb) methodology with corresponding control groups. Plasma cholinesterase activity was decreased by 13% and 24% respectively in males and females (6 rats/sex) within two hours following exposure to 6 ppb (whole-body). There were no-decreases in plasma cholinesterase activity in male or female rats within two hours following exposure to 3.5 ppb (whole-body) or 14 ppb (nose-only).

Male and female rats (6/sex) from the 6 ppb whole-body and 14 ppb nose-only groups were held for a two-week observation period after exposure. Plasma cholinesterase activity was not decreased 2 weeks after exposure to 6 ppb. There were no signs of toxicity based on general observations, body weights, or gross pathology. The decrease in plasma cholinesterase activity following whole-body exposure to 6 ppb, was probably due to contamination of the fur and subsequent oral ingestion and/or dermal absorption. The nose-only method was a better defined inhalation exposure method for this material.

The small decreases in plasma cholinesterase were considered to be an indication of exposure rather than toxicity. Since vapor exposures up to approximately 60% of the maximum theoretically attainable concentration (14 ppb/25 ppb) caused no significant toxicity, the test substance does not appear to have a significant acute vapor inhalation exposure hazard.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

258 mg/m³ air

Quality of whole database:

Two acute inhalation toxicity studies were conducted on rat. 4 hours study tested in according to GLP is considered as key study.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Specific details on test material used for the study:

Sample ID: AGR 214637
Purity: 98.5%

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Type of coverage:

other: gauze dressing and non-irritating tape with plastic cuff placed over the trunk of the animal

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Statistics:

Means and standard deviations were calculated for body weights. The data was evaluated for statistical outliers by a sequential test (Grubbs, 1969), however when found, were not excluded from statistical procedures.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Red soiling around the eyes in three males and one female was the only clinical sign observed during the study.

Gross pathology:

All animals were within normal limits at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 (Rat): >2000 mg/kg

Executive summary:

The test substance was evaluated for dermal toxicity according to the guidelines EPA OPPTS 81-2. Five Fischer 344 rats per sex received a single dermal application of 2000 mg/kg body weight. All males and females survived until study termination (two weeks post-treatment) in apparent good health. The acute dermal LD50 for males and females was greater than 2000 mg/kg. All animals were within normal limits at necropsy. Based on these results, the acute dermal toxicity of this material was categorized as low.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Substance ID: TSN100759
Lot #: 7299412
Purity: 97.6%

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: 4 to 5 months
- Weight at study initiation: 2.184 to 2.649 kg
- Diet: 4 ounces per day
- Water: ad libitum
- Acclimation period: Atleast 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 19±3°C
- Humidity: 39 - 61%
- Air changes: 15 per hr
- Photoperiod: 12 hrs dark/12 hrs light

Type of coverage:

other: gauze patch was held in place by an elastic rabbit jacket

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 10 by 14 cm
- % coverage: 10% of the surface area of the rabbits
- Type of wrap if used: Gauze patch was held in place by an elastic rabbit jacket

REMOVAL OF TEST SUBSTANCE
- Washing: Skin was wiped thoroughly with a water moistened soft disposable towel and dried with a soft disposable towel
- Time after start of exposure: Approximately after 24-hour exposure period

TEST MATERIAL
- For solids, paste formed: Yes, melted to liquid

Duration of exposure:

24 hours

Doses:

2000 mg/kg, 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The rabbits were weighed prestudy, the day of treatment and on test days 2, 8 and 15
- Necropsy of survivors performed: yes

Statistics:

Means and standard deviations were calculated for body weights. The data were evaluated for statistical outliers by a sequential test (Grubbs, 1969), however, outliers were not routinely excluded from statistical analysis.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Two males and one female administered 5000 mg/kg had fecal soiling in the perineal area on test days 1 or 2. Treatment-related dermal alterations at the application site consisted of erythema, edema, fissures and scaling in animals administered 5000 mg/kg

Gross pathology:

There were no treatment-related gross pathologic observations.

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 (Rabbit): >5000 mg/kg

Executive summary:

The test substance was evaluated for dermal toxicity according to the guidelines OECD 402 and EPA OPPTS 81-2. Five New Zealand White rabbits per sex per dose level received a single, 24-hour, dermal exposure of 2000 or 5000 mg/kg. Parameters evaluated included body weights, in-life observations and gross pathologic evaluation.

All rabbits administered 2000 or 5000 mg/kg (the limit test established by the guidelines) survived. No substantial weight change was observed during the two-week observation period.

Two males and one female administered 5000 mg/kg had fecal soiling in the perineal area on test days 1 or 2. Treatment-related dermal alterations at the application site consisted of erythema, edema, fissures and scaling in animals administered 5000 mg/kg; erythema and scaling were observed in animals administered 2000 mg/kg. All dermal alterations had resolved in all animals by the end of the 14-day observation period, with the exception of scaling that persisted at the application site of one female administered 5000 mg/kg. There were no treatment-related gross pathologic observations.

Under the conditions of this study, the acute dermal LD50 of the test substance was greater than 5000 mg/kg, the limit dose tested, for male and female New Zealand White rabbits.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Dursban Technical
Lot # EK 830516110
Purity: Not reported

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the observation period

Clinical signs:

other: Occasional signs of chromodacryorrhoea was noted during the day of dosing. Other occasional signs noted during the study period were lethargy (days 1-3), hunched posture (days 2 and 3), piloerection (days 2-5), chromodacryorrhoea (days 1-5) and exothalmia

Gross pathology:

All animals were necropsied. Pathological findings were uncommon. Three animals (2 male, 1 female) showed dark livers at necropsy. Remaining animals were unremarkable.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (Rat): >2000 mg/kg

Executive summary:

A study was performed to determine the acute dermal median lethal dose of the test substance in the rat. The study was designed to meet the requirements of OECD guideline 402. A group of 10 Sprague Dawley-derived rats (5 males, 5 females) was given a single, 24 hour, dermal application of the test substance at a dose level of 2000 mg/kg. No animals died during the 14 day observation period. The acute dermal median lethal dose of the test substance in the rat was in excess of 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Three acute dermal toxicity studies were conducted on rat and rabbit. Rabbit study tested in according to OECD guideline 402, EPA 81-2 is considered as key study

Additional information

In the acute oral toxicity study, rats were tested in according to OECD guideline 423 and EPA OPPTS 870.1100, Chlorpyrifos was administered at dose levels of 50, 300, 2000 mg/kg body weight. Clinical signs like lethargy, tremors, abdominal breathing and chromodacryorrhea were observed after dosing and all animals were found dead at both 300, 2000 mg/kg doses. Visceral examination revealed congestion of the liver and lungs with no external abnormalities. No signs of toxicity, including clinical signs and body weight recording, were observed in any rat treated at the dose level of 50 mg/kg body weight during the whole observation period. The LD50 was found to be 200 mg/kg body weight.   

 

In an acute inhalation toxicity rat study, 200 mg/m3 of chlorpyrifos vapours are exposed for 4 hours. During the exposure period the rats showed clear signs of reaction to the vapour including salivation eye closing etc. There were no mortalities in this study nor were there any significant observations after the first day. It was concluded that the LC50 is greater than 200 mg/m3 (14 ppm) and that the hazard associated with inhalation is likely to be low.   

     

In the acute dermal rabbit toxicity study, Chlorpyrifos was administered to at dose levels of 2000 and 5000 mg/kg body weight. All rabbits administered 2000 or 5000 mg/kg survived. No substantial weight change was observed during the two-week observation period. Two males and one female administered 5000 mg/kg had fecal soiling in the perineal area on test days 1 or 2. Under the conditions of this study, the acute dermal L050 was greater than 5000 mg/kg. 

Justification for classification or non-classification

Based on the acute oral LD50 of 200 mg/kg in rats, classifications of acute oral Category 3 can be considered.

Based on dermal LD50 in rats and rabbits of >5000 and >2000 mg/kg, it is concluded that chlorpyrifos should is not classified as for Acute toxicity-dermal.

Based on 4-hour acute inhalation LC50 of > max attainable concentration, it is concluded that chlorpyrifos is not classified as for Acute toxicity-inhalation