Chlorpyrifos

Endpoint summary

Description of key information

Study Type	Species	Findings	Guideline	Reliability
Skin	Rabbit	No irritation	OECD 404, EPA 81-5, EU Method B.4	1
Skin	Rabbit	No irritation	OECD 404	2
Eye	Rabbit	Slight irritation cleared by 72 hours	OECD 405, EPA 81-4, EU Method B.5	1
Eye	Rabbit	Slight irritation cleared by 72 hours	OECD 405	2

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAFF Primary Dermal Irritation Study, 1985

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: Approximately 4 months
- Weight at study initiation: 2.044-2.598 kg
- Housing: Housed individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 3
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL (The crystalline test substance was gently heated to achieve a liquid state)
- Concentration: Neat

Duration of treatment / exposure:

4 hours

Observation period:

30 minutes, and 24, 48 and 72 hours

Number of animals:

Three male and three female animals

Details on study design:

TEST SITE
- Area of exposure: 10 x 10 cm
- Type of wrap if used: Elastic rabbit jacket

REMOVAL OF TEST SUBSTANCE
- Washing: The back was wiped with a damp disposable towel to remove any residual test substance
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30 minutes, and 24, 48 and 72 hours

SCORING SYSTEM:
- Method of calculation: Draize system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight erythema was present at the application site of all rabbits, and very slight edema was present at the application site of two rabbits, within 30 minutes after the four-hour exposure. One additional rabbit had very slight edema at the application site 24 hours after exposure. The erythema and edema resolved in all rabbits by 7 days after test material removal, and the test was then terminated.

Other effects:

Dermal application of 0.5 ml of the test subtance had no effect on body weight.

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating in rabbits

Executive summary:

The study was conducted following OECD guideline 404 and EPA guideline 81-5. The test substance was evaluated for primary dermal irritation. Aliquots of 0.5 ml of neat test substance were applied for four hours to the intact skin on the back of six New Zealand White rabbits.

Very slight erythema was present at the application site of all rabbits, and very slight edema was present at the application site of two rabbits, within 30 minutes after the four hour exposure. One additional rabbit had very slight edema at the application site 24 hours after exposure. The erythema and edema resolved in all rabbits by 7 days after test material removal, and the test was then terminated. Body weights were not affected.

Reference 2

Endpoint:

skin irritation: in vivo

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Dursban Technical
Lot Number: EK 830516110
Purity: Not reported

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: distilled water

Controls:

no

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

Three female rabbits

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

One test site showed very slight redness at 1 hour after removal of the patches in one animal. The other test sites appeared normal. All treated sites were normal at the 24, 48, and 72-hour observation.

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating in rabbits

Executive summary:

A study was performed to determine the primary skin irritation index and corrosive effects of the test substance in the New Zealand White rabbit.

The study was designed to meet the requirements of the OECD Guideline 404.

A single, 4 hour occluded dermal application of the test substance produced a primary irritation index of 0. The test article was classified as a non-irritant to rabbit skin. No corrosive effects were noted.

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Justification for type of information:

Conduct of an In vivo study is a data requirement in other geographies (Asian countries such as India, China, Japan etc.) and therefore, an in vivo study was conducted which was adequate to evaluate the endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAFF Primary Eye Irritation Study, 1985

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: Approximately 5 months
- Weight at study initiation: 2.243-2.634 kg
- Housing: Housed individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 3
- Humidity (%): 40-60
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (The crystalline test material was gently heated to achieve a liquid state).
- Concentration: Neat

Duration of treatment / exposure:

The eyelids were gently held together for approximately one second in order to prevent loss of the test substance. The eyes of all rabbits remained unwashed post treatment.

Observation period (in vivo):

Approximately 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Three male and three female animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Unwashed

SCORING SYSTEM: Draize scoring method

TOOL USED TO ASSESS SCORE: Penlight

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness and discharge

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight conjunctival redness was observed in the treated eyes of all rabbits one hour after dosing. Three rabbits had slight chemosis, and two rabbits had slight ocular discharge one hour after dosing. The ocular irritation was resolved in all rabbits by 24 hours after test substance administration, and the test was terminated 72 hours after test substance administration.

Other effects:

Instillation of the test substance into the eye had no effect on body weights.

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating in rabbits

Executive summary:

The study was conducted according to OECD guideline 405 and EPA guideline 81-4. The test substance was assessed for the potential to cause ocular irritation after instillation of a 0.1 mL aliquot of neat test material into the conjunctival sac of the right eye of six New Zealand White rabbits.

Slight conjunctival redness was observed in the treated eyes of all rabbits one hour after dosing. Three rabbits had slight chemosis, and two rabbits had slight ocular discharge one hour after dosing. The ocular irritation was resolved in all rabbits by 24-hours after test substance administration. The test was terminated 72 hours after test substance administration. Instillation of the test substance into the eye had no effect on body weight.

Reference 2

Endpoint:

eye irritation: in vivo

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Specific details on test material used for the study:

Dursban Tech
Lot Number: EK 830516110
Purity: Not reported

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye

Duration of treatment / exposure:

A 'cup' was formed by gently pulling the lower lid of the left eye away from the eyeball and the test substance (100 mg) placed inside. Both the upper and lower lids were then held together for 1 - 2 seconds and the animal was released. The untreated right eye served as a control..

Observation period (in vivo):

Approximately 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

Three female rabbits

Irritation parameter:

conjunctivae score

Remarks:

redness, chemosis and discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

20

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness, chemosis and discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

20

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness, chemosis and discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

20

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

80

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

80

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

80

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

10

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

10

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

10

Remarks on result:

no indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

110

Remarks on result:

no indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

110

Remarks on result:

no indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

110

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight transient conjunctivitis was noted in all treated eyes 1 hour after treatment. Slight iridial inflammation was noted in 1 animal at this time. All treated eyes recovered and appeared normal on day 1.

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating in rabbits
Slight irritant according to modified Kay and Calandra scoring system

Executive summary:

A study was performed to assess the irritant effects of the test substance on the eye of the New Zealand White rabbit.

The study was designed to meet the requirements of the OECD guideline 405.

The instillation of test substance produced slight transient conjunctivitis in all treated eyes 1 hour after treatment. Slight iridial inflammation was noted in 1 animal at this time. All treated eyes recovered and appeared normal on day 1.

The eye irritation scores were interpreted by a modified Kay and Calandra scoring system and the test article was classified as slight irritant (classification 3).

The test article was classified as a non-irritant according to the EEC Commission Directive 67/548/EEC for the classification, packaging and labelling of dangerous substances

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Justification for type of information:

Conduct of an In vivo study is a data requirement in other geographies (Asian countries such as India, China, Japan etc.) and therefore, an in vivo study was conducted which was adequate to evaluate the endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In two acute dermal irritation studies in rabbits conducted according to OECD guideline 404, no dermal irritation was noted.  

     

In two acute eye irritation studies in rabbits conducted according to OECD guideline 405, slight conjunctival redness was observed in the treated eyes of all rabbits one hour after dosing. Three rabbits had slight chemosis, and two rabbits had slight ocular discharge one hour after dosing. The ocular irritation was resolved in all rabbits by 24 hours after test material administration. It is therefore considered that Chlorpyrifos is non-irritant to the eyes.

Justification for classification or non-classification

The test substance produced no skin irritation and, therefore, does not need to be classified for skin irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. The substance also does not need to be classified for eye irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. In the study, slight conjunctival redness was observed in the treated eyes of all rabbits one hour after dosing. Three rabbits had slight chemosis, and two rabbits had slight ocular discharge one hour after dosing. The ocular irritation was resolved in all rabbits by 24 hours after test material administration. It is therefore considered that Chlorpyrifos is non-irritant to the eyes.