O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

Endpoint summary

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

Study period:

26 October 2005 to 10 November 2005

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Single application

Observation period:

72 hrs

Number of animals:

3 animals

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

1.7

Max. score:

2

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

1.3

Max. score:

2

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

1.7

Max. score:

2

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

1.3

Max. score:

2

Reversibility:

not specified

Individual skin irritation scores are presented below, All animals appeared active and healthy. Apart from the skin irritation noted below, there were no other signs of gross toxicity, adverse pharmacological effects or abnormal behaviour.

 

One hour after patch removal, well defined erythema and slight oedema were noted for all three treated sites. The overall incidence and severity of irritation decreased with time. Apart from desquamation noted at all dose sites on Day 7, all animals were free from dermal irritation by study terminatin (Day 7).

 

The Primary Dermal Irritation Index for Profenofos Technical is 3.1.

 

Table 7.3.1-1: Individual and mean skin irritation scores according to the Draize scheme

	Erythema/Oedema
Animal no	15535/M	15536/F	15537/M	Total
	4 HOUR EXPOSURE
1 hr	2/2	2/2	2/2	6/6
24 hr	2/2	2/2	2/1	6/5
48 hr	1/1	2/1	2/1	5/3
72 hr	1/0	1/0	2/1	4/1
7 days	0/0*	0/0*	0/0*	0/0*
Mean	2.0/2.0	2.0/1.7	1.7/1.0	1.3/0.7

* Desquamation present at dose site

Conclusions:

Under the conditions of this study, the test material is classified as moderately irritating to the skin.

Executive summary:

In a primary dermal irritation study,3 young adult New Zealand rabbits, 2 males and 1 females, were exposed via the dermal route to 0.5 mL of Profenofos Technical/animal. The test material was administered semi occluded as supplied for 4 hours to a clipped area of intact skin measuring ~1 inch². Animals were then observed for 7 days. Irritation was scored using the Draize scheme.

 

Under the conditions of this study, the test material is classified as moderately irritating to the skin.

Reference 2

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

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

7 September to 10 September 2004

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Single application

Observation period:

72 hrs

Number of animals:

3 animals

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

1

Reversibility:

not specified

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Individual skin irritation scores are presented below, All animals appeared active and healthy. Apart from the skin irritation noted below, there were no other signs of gross toxicity, adverse pharmacological effects or abnormal behaviour.

 

One hour after patch removal, very slight to well-defined erythema and very slight oedema were noted for all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 72 hours.

 

The Primary Dermal Irritation Index for Profenofos Technical is 1.2.

 

Table 7.3.1 -2: Individual and mean skin irritation scores according to the Draize scheme

	Erythema/Oedema
Animal no	12553/F	12554/M	12555/F	Total	Mean
	4 HOUR EXPOSURE
1 hr	1/1	1/1	2/1	4/3	1.3/1
24 hr	1/0	1/0	1/1	3/1	1.0/0.3
48 hr	1/0	0/0	1/1	2/1	0.7/0.3
72 hr	0/0	0/0	0/0	0.0	0.0/0.0
Mean	0.33	0.17	0.67	-	0.39

 

Conclusions:

Under the conditions of this study, the test material is described as slightly irritating to the skin.

Executive summary:

In a primary dermal irritation study,3 young adult New Zealand rabbits, 1 males and 2 females, were exposed via the dermal route to 0.5 mL of Profenofos Technical/animal. The test material was administered semi occluded as supplied for 4 hours to a clipped area of intact skin measuring ~1 inch². Animals were then observed for 3 days. Irritation was scored using the Draize scheme.

 

Under the conditions of this study, the test material is described as slightly irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 November 2005 to 12 November 2005

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF 12 Nouan No. 8147 (2000)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72hr post dosing

Number of animals or in vitro replicates:

1 male and 2 female rabbits

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Findings are summarised below

 

Table 7.3.2-1: Eye irritation scores according to the Draize scheme

Time/ Rabbit	Rabbit 1				Rabbit 2				Rabbit 3
	Hours				Hours				Hours
	1	24	48	72	1	24	48	72	1	24	48	72
I. Cornea
A. Opacity	0	0	0	0	0	0	0	0	0	0	0	0
B. Area	4	4	4	4	4	4	4	4	4	4	4	4
(AxB)x5	0	0	0	0	0	0	0	0	0	0	0	0
II. Iris
A. Values	0	0	0	0	0	0	0	0	0	0	0	0
Ax5	0	0	0	0	0	0	0	0	0	0	0	0
III. Conjunctivae
A. Redness	2	1	0	0	2	1	0	0	2	1	0	0
B. Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C. Discharge	3	1	0	0	3	1	0	0	3	1	0	0
(A+B+C)x2	12	4	0	0	12	4	0	0	12	4	0	0
Total	12	4	0	0	12	4	0	0	12	4	0	0

 Additional criteria in Directive 93/21/EEC Point 3.2.6.2 fulfilled: Yes

 

All animals appeared active and healthy during the study apart from the eye irritation noted, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

 

No corneal opacity or iritis was noted for any treated eye during the study. One hour after test material instillation conjunctivitis was noted for all three treated eyes. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hours.

 

The maximum mean total score of Profenofos Technical was 12.0

Conclusions:

Based on the results of this study, Profenofos Technical is classified as mildly irritating to the eye.

Executive summary:

In a primary eye irritation study, 0.1 mL Profenofos Technical (undiluted) was instilled into the conjunctival sac of the right eye of three young adult New Zealand White rabbits. The left eye acted as a control. Animals were then observed for 3 days. Irritation was scored using the Draize scheme for unwashed eyes, with the system of Kay and Calandra used to classify the test material.

 

All animals appeared active and healthy during the study apart from the eye irritation noted, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

 

No corneal opacity or iritis was noted for any treated eye during the study. One hour after test material instillation conjunctivitis was noted for all three treated eyes. The overall incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 72 hour

 

Based on the results of this study, Profenofos Technical is classified as mildly irritating to the eye.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

9 September 2004 to 12 September 2004

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF59 NohSan No. 4200 (1985)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72hr post dosing

Number of animals or in vitro replicates:

3 male rabbits

Irritation parameter:

overall irritation score

Basis:

mean

Score:

ca. 10.7

Reversibility:

fully reversible within: 48 hrs

Remarks on result:

other: Classified as minimally irritating

Findings are summarised below

 

Table 7.3.2 -2: Eye irritation scores according to the Draize scheme

Time/ Rabbit	Rabbit 1				Rabbit 2				Rabbit 3
	Hours				Hours				Hours
	1	24	48	72	1	24	48	72	1	24	48	72
I. Cornea
A. Opacity	0	0	0	0	0	1	0	0	0	0	0	0
B. Area	4	4	4	4	4	1	4	4	4	4	4	4
(AxB)x5	0	0	0	0	0	5	0	0	0	0	0	0
II. Iris
A. Values	0	0	0	0	0	0	0	0	0	0	0	0
Ax5	0	0	0	0	0	0	0	0	0	0	0	0
III. Conjunctivae
A. Redness	2	1	0	0	2	1	0	0	2	1	0	0
B. Chemosis	1	0	0	0	1	0	0	0	2	1	0	0
C. Discharge	2	1	0	0	2	1	0	0	2	1	0	0
(A+B+C)x2	10	4	0	0	10	4	0	0	12	6	0	0
Total	10	4	0	0	10	9	0	0	12	6	0	0

 Additional criteria in Directive 93/21/EEC Point 3.2.6.2 fulfilled: Yes

 

One animal exhibited soft faeces. The remaining animals appeared active and healthy during the entire study.

 

Within one hour after test material instillation, conjunctivitis was observed in all three treated eyes. One animal developed corneal opacity at 24 hours. All animals were free of ocular irritation within 48 hours.

 

The maximum mean total score of Profenofos Technical was 10.7

Conclusions:

Based on the results of this study, Profenofos Technical (CGA15324) is described as minimally irritating to the eye. Positive effects cleared by 48 hours.

Executive summary:

In a primary eye irritation study, 0.1 mL Profenofos Technical (undiluted) was instilled into the conjunctival sac of the right eye of three young adult New Zealand White rabbits. The left eye acted as a control. Animals were then observed for 3 days. Irritation was scored using the Draize scheme for unwashed eyes.

 

Within one hour after test material instillation, conjuctivitis was observed in all three treated eyes. One animal developed corneal opacity at 24 hours. All animals were free of ocular irritation within 48 hours.

 

Based on the results of this study, Profenofos Technical (CGA15324) is described as minimally irritating to the eye. Positive effects cleared by 48 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The key study on Profenofos (purity 89%) reports that this test material is moderately irritating (mean irritation score of 12). The supporting study, in which a slightly higher purity (92.1%) of Profenofos was tested returned a result of minimally irritating (mean irritation score of 10.4). In both cases the irritation observed was fully reversible, either within 72 or 48 hours, respectively.

 

Eye irritation

The key study on Profenofos (purity 92.1%) reports that the test material was mildly irritating (mean irritation score of 10.4). The supporting study, in which a slightly lower purity (89%) of Profenofos was tested returned a result of mildly irritating (mean irritation score of 12). In both cases the irritation observed was fully reversible, either within 48 or 72 hours, respectively.

 

Respiratory irritation

Currently there are no guideline approved studies which have the objective to address respiratory irritation adequately. However, clinical toxicity data from the acute inhalation studies (Rattray, 2004 and Horath, 1982) were indicative of irritation of the respiratory tract (increased breathing rate and abnormal respiratory noise in some animals) post exposure.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Although in both eye and skin irritation studies results indicates Profenofos is slightly/moderately irritating to eyes and skin, according to Regulation (EC) No 1272/2008 Prodenofos is not classified as an eye or skin irritant.