Mecoprop

Endpoint summary

Description of key information

Skin Sensitisation In Vivo: Kirsch (1984)

Under the conditions of this study, the skin sensitising potential of the test material is inconclusive due to the high percentage of control animals that exhibit the same reactions as the test animals.

 

Skin Sensitisation In Vivo: Grundler (1984)

Under the conditions of this study, the test material was found to have no skin sensitising effect.

 

Skin Sensitisation In Vitro: Waiver

An in vitro skin sensitisation study does not need to be conducted because adequate data from in vivo skin sensitisation studies are available.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 August 1983 to 15 September 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study pre-dates the introduction of the LLNA method.

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Preparation of the test material formulations: Immediately before test material application with Ultraturrax or with a magnetic stirrer. Formulations of the test material were prepared gravimetrically. The test material was prepared in at appropriate concentrations in distilled water (aqua dest.), distilled water and paraffin oil or distilled water and Freund's adjuvant (FCA).

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Not specified
- Weight at study initiation: 264 - 329 g
- Housing: Macrolon, type IV cages. 5 animals per cage.
- Diet: Ad libitum
- Water : Ad libitum, tap water; about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week.
- Acclimation period: At least 7 Days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hours light (6.00 - 18.00 hours) / 12 hours darkness (18.00 - 6.00 hours)

Route:

intradermal

Vehicle:

water

Concentration / amount:

10 % w/w in paraffin oil/aqua dest. (1:1), FCA/ aqua dest (1:1)

Day(s)/duration:

Treatment on Day 1

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

other: Percutaneous, occlusive

Vehicle:

water

Concentration / amount:

50 % w/w (about 0.3 g)

Day(s)/duration:

Treatment 7 Days after indradermal induction for 48 hours

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

other: percutaneous, occlusive

Vehicle:

water

Concentration / amount:

10 % w/w

Day(s)/duration:

Treatment 14 days after percutaneous application

Adequacy of challenge:

highest non-irritant concentration

No.:

#2

Route:

other: percutaneous, occlusive

Vehicle:

water

Concentration / amount:

10 % w/w

Day(s)/duration:

One week after first challenge

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 animals per test group, 10 animals per control group

Details on study design:

PRETESTS:
2 x 2 cm filter paper strips were applied to the skin of the flanks under an occlusive dressing. In the case of liquids the test filter paper strip is soaked in the test material formulation; in the case of solid substances the paper strip is coated with an approx. 0.5 mm thick layer of the test material formulation; thus, the animals were exposed to about 0.15 g of the test material formulation. Exposure period was 24 Hours, there were four test animals per concentration and there were readings 24, 48 and 72 hours after the beginning of application.

In the pretest, with percutaneous occlusive application, a 25 % aqueous formulation of the test material was found to be the minimum irritant concentration and a 25 % aqueous test substance formulation the maximum non-irritant con­centration. Since in an initial test with a challenge with 25 % aqueous test material concentration, unclear test results were obtained (skin reactions in control and test animals), the concentration of the challenge was reduced to 10 % in the present investigation.

MAIN STUDY
A. INDUCTION EXPOSURE
- Intradermal induction: 6 intradermal injections in groups of two per animal
- Exposure period: 48 Hours
- Test groups: (A) Front row: 2 injections each of 0.1 mL Freund's adjuvant without test material emulsified with water in a ratio of 1:1. (B) Middle row: 2 injections each of 0.1 mL of the test material formulation. (C) Back row: 2 injections each of 0.1 mL Freund's adjuvant / water (1:1) with test material
- Control group: The animals were given the same injections but without the test material, only with the formulating agent
- Site: Shoulder
- Readings: 24 hours after the beginning of application

- Percutaneous induction: 0.3 g of test material formulation was applied by means of 2 x 4 cm filter strip to the skin of the shoulder under an occlusive dressing.
- Exposure period: 48 hours
- Control groups: Control animals were not treated since the distilled water used as a formulating agent was not expected to influence the result of the study
- Site: Shoulder
- Readings: 48 hours after the beginning of application

B. CHALLENGE EXPOSURE
- Challenge 1: 0.15 g of test material formulation was applied by means of 2 x 2 cm filter strip to the skin of the flank under an occlusive dressing. Test group and control group one received treatment with test material formulation (control without test material), control group remained untreated.
- Challenge 2: Amount applied and method of application was the same as challenge one. Test group and both control groups one and two received test material formulation (controls without test material)
- Days of challenge: Challenge 1 was 19 days after intradermal induction, challenge 2 began 26 days after intradermal induction.
- Exposure period: 24 Hours
- Site: intact clipped flanks
- Concentrations: 10 % (w/w) of test material in aqua dest.
- Readings: 24, 48 and 72 hours after the beginning of application

OTHER:
- Preparation of animals: Clipping of the test animals, if required, was completed 3 to 5 hours before each reading and before each test material application at the appropriate application sites.
- Clinical examinations: No detailed examinations; a check for sick animals and for those showing deteriorated general state each workday.
- Bodyweight: Animals were weighed before each test material application and before the end of the study
- Scoring:
Erythema and eschar formation:
No erythema = 0
Very slight erythema (barely perceptible) = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) = 4

Oedema formation
No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edges of area well defined by definite raising) = 2
Moderate oedema (raised approximately 1 mm) = 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) = 4

Challenge controls:

A formulating agent was used that was not expected to influence the result of the test.

Positive control substance(s):

no

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

10 % w/w in aqua dest.

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10 % w/w in aqua dest.

No. with + reactions:

3

Total no. in group:

19

Clinical observations:

Very slight erythema, and very slight edema

Remarks on result:

positive indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

10 % in aqua dest

No. with + reactions:

8

Total no. in group:

10

Clinical observations:

Very slight erythema, thin scab-like layers

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10 % w/w in aqua dest.

No. with + reactions:

15

Total no. in group:

19

Clinical observations:

Very slight erythema, thin scab-like layers

Remarks on result:

positive indication of skin sensitisation

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

10 % in aqua dest.

No. with + reactions:

3

Total no. in group:

20

Clinical observations:

Very slight erythema

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

10 % w/w in aqua dest.

No. with + reactions:

14

Total no. in group:

19

Clinical observations:

Very slight erythema, and very slight edema

Remarks on result:

positive indication of skin sensitisation

Reading:

rechallenge

Hours after challenge:

72

Group:

negative control

Dose level:

10 % w/w aqua dest

No. with + reactions:

13

Total no. in group:

20

Clinical observations:

Very slight erythema, thin scab-like layers

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

rechallenge

Hours after challenge:

72

Group:

test chemical

Dose level:

10 % w/w aqua dest

No. with + reactions:

17

Total no. in group:

19

Clinical observations:

Very slight erythema, and very slight edema, thin scab-like layers

Remarks on result:

positive indication of skin sensitisation

The Number of Animals with Skin Findings in Challenge Trials

	1st challenge		2nd challenge
	10 % in aqua dest.
	48 h after application	72 h after application	48 h after application	72 h after application
Control group 1	0/10	8/10	3/10	6/10
Control group 2	untreated		0/10	7/10
Test group*	3/19	15/19	14/19	17/19

 

x/y: Number of skin changes/number of guinea pigs tested

*1/20 animals died from pneumonia 20 days after the intradermal injection

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the skin sensitising potential of the test material is inconclusive due to the high percentage of control animals that exhibit the same reactions as the test animals.

Executive summary:

The sensitising potential of the test material was investigated similar to OECD Test Guideline 406 and in accordance with GLP.
20 female guinea pigs were initially subjected to an intradermal induction, where they each received 6 injections in groups of two into the shoulder. Two injections contained 0.1 mL FCA without test material emulsified with water in a ratio 1:1, two injections contained 1 mL of the test material formulation (10 % (w/w) in distilled water), and finally two injections contained 0.1 mL FCA in water (1:1) with test material. After intradermal induction, distinct erythema and oedema were observed at the injection sites of the test animals and also in the case of the control animals that only received Freund's adjuvant or paraffin oil and aqua dest. (1:1) without test material; 11 test animals had necrotic skin changes. Percutaneous induction was carried out a week later, where 50 % w/w test material in distilled water was added to the same area of skin via a filter paper strip. The site was exposed for 48 hours. Percutaneous induction was only carried out in the case of the guinea pigs of the experiment group, incrustation being observed in addition to distinct erythema and oedema. No application was made to the control animals, since, with aqua dest., a vehicle was used that was not expected to influence the result of the test.
Two challenges were then undertaken, with the first beginning 19 days after the intradermal induction. The test material was applied to the clipped flank of the animals by percutaneous application (conc. 10 % w/w in aqua dest.), for 24 hours. In contrast to the percutaneous induction, the skin findings observed in the two challenges are almost without exception merely very slight, scarcely perceptible reactions: erythema and thin scab-like layers and in the 2nd challenge also isolated cases of oedema were observed.
At the readings after 48 hours the number of animals with skin findings in the test group is appreciably higher than that in control group 1. However, as a result of evidently delayed reactions, the ratio of guinea pigs with skin changes to the number of animals used is in the same range in the control groups as in the test group at the readings after 72 hours.
Under the conditions of this study, the skin sensitising potential of the test material is inconclusive due to the high percentage of control animals that exhibit the same reactions as the test animals.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

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

Justification for type of information:

An in vitro skin sensitisation study does not need to be conducted because adequate data from in vivo skin sensitisation studies are available.

Reference 3

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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:

no guideline followed

Principles of method if other than guideline:

An Open Epicutaneous Test (OET) was performed to assess the skin sensitising potential of the test material investigated in a test model that takes greater account of the concentration dependence and also permits a practice-related assessment.

GLP compliance:

not specified

Type of study:

open epicutaneous test

Justification for non-LLNA method:

The study pre-dates the inception of the LLNA guideline.

Species:

guinea pig

Route:

epicutaneous, open

Vehicle:

not specified

Concentration / amount:

50, 15, 5 and 1.5 % (w/w)

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#2

Route:

epicutaneous, open

Vehicle:

not specified

Concentration / amount:

50, 15, 5 and 1.5 % (w/w)

Adequacy of challenge:

not specified

No. of animals per dose:

8 animals per dose in control groups

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- Exposure period: Four weeks
- Concentrations: 50, 15 5 and 1.5 %

B. CHALLENGE EXPOSURE:
- Concentrations: 50, 15, 5 and 1.5 %
- Evaluation (hr after challenge): 24, 48 and 72 hours

Positive control substance(s):

no

Dose level:

1.5 %

Remarks on result:

no indication of skin sensitisation

Dose level:

5 %

Remarks on result:

no indication of skin sensitisation

Induction:

The skin changes during induction that only occurred after several applications and were caused mainly by 50 and 15 % test material formulations, did not exhibit any appreciable increase in intensity during the 4-week period of treatment (maximally slight erythema, very slight scarcely perceptible oedema and in some cases scale formation). In the case of a contact allergen an intensification of the findings would have been expected in the course of the 20 applications of the test material.

 

First challenge:

At the 1st challenge no animal showed any reaction 24 hour after application.

48 hours after application, in the case of the animals challenged with 50 and 15 %, the number of guinea pigs with skin reactions in the control group was lower than in the pretreated groups, which reacted in the same way qualitatively and quantitatively in­dependently of the induction concentration.

At the reading after 72 hours, however, the number of guinea pigs with skin changes in the control group had increased to 7 out of 8 animals at the 50 % challenge concentration and to 4 out of 8 at the 15 % one.

 

Second challenge:

At the second challenge slight skin reactions occurred even 24 hours after application at the 50 % concentration and in some cases also at the 15 % challenge concentrations in the animals that had already been challenged. This applies equally to the animals of control group 1 and to all test groups pre­treated at the various concentrations. Only control group 2, in which the animals had not previously been contacted with the test material, showed no reaction.

48 hours after the 2nd challenge, a skin reaction was also detect­able in most of the animals of control group 2 in the same way as the treated animals and control group 1 at the 50 and 15 % challenge concentrations.

72 hours after the 2nd challenge the number of guinea pigs with skin changes had increased further in several test groups and in the 2nd control group at the 15 % challenge concentration.

 

Overall:

As a rule the challenge with 5 and 1 .5 % test material formulations proceeded without any apparent reaction. Merely some control and test animals exhibited scarcely perceptible erythema at the 5 % challenge.
On the basis of the reduction of the reaction threshold in pre­treated animals in comparison with control animals that have not had any contact with the test material, it is the aim of the OET to demonstrate a sensitisation in dependence on the induction and challenge concentrations. Since in this test reactions were ob­served in very isolated cases at the 5 % challenge and in both pre­treated and non-pretreated animals at higher concentrations, the test material did not exhibit a sensitising potential in the OET. Furthermore, conclusions about a possible sensitising potential of the test material may also be drawn from the course of the reactions during induction in the OET. Contact allergens cause an appreciable in­crease in skin reactions from the 3rd week of induction onward.

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the test material was found to have no skin sensitising effect.

Executive summary:

The skin sensitising potential of the test material was investigated using the Open Epicutaneous Test (OET).

The test material concentration selected for the induction and challenge tests were 50, 15, 5 and 1.5 %. During the induction, skin changes only occurred at the two highest concentrations of test material formulation (50 and 15 %) after several applications and did not show an appreciable increase in intensity during the four-week treatment period. After the two challenges, scarcely any qualitative or quantitative differences were found between the control and test groups. Test reactions were observed in very isolated cases at the 5 % challenge and in both pre-treated and non-pretreated animals at higher concentrations, therefore it can be concluded that the test material does not exhibit sensitising potential in the OET.

Under the conditions of this study, the test material was found to have no skin sensitising effect.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitisation: Kirsch (1984)

The sensitising potential of the test material was investigated similar to OECD Test Guideline 406 and in accordance with GLP. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).
20 female guinea pigs were initially subjected to an intradermal induction, where they each received 6 injections in groups of two into the shoulder. Two injections contained 0.1 mL FCA without test material emulsified with water in a ratio 1:1, two injections contained 1 mL of the test material formulation (10 % (w/w) in distilled water), and finally two injections contained 0.1 mL FCA in water (1:1) with test material. After intradermal induction, distinct erythema and edema were observed at the injection sites of the test animals and also in the case of the control animals that only received Freund's adjuvant or paraffin oil and aqua dest. (1:1) without test material; 11 test animals had necrotic skin changes. Percutaneous induction was carried out a week later, where 50 % w/w test material in distilled water was added to the same area of skin via a filter paper strip. The site was exposed for 48 hours. Percutaneous induction was only carried out in the case of the guinea pigs of the experiment group, incrustation being observed in addition to distinct erythema and oedema. No application was made to the control animals, since, with aqua dest., a vehicle was used that was not expected to influence the result of the test.
Two challenges were then undertaken, with the first beginning 19 days after the intradermal induction. The test material was applied to the clipped flank of the animals by percutaneous application (conc. 10 % w/w in aqua dest.), for 24 hours. In contrast to the percutaneous induction, the skin findings observed in the two challenges are almost without exception merely very slight, scarcely perceptible reactions: erythema and thin scab-like layers and in the 2nd challenge also isolated cases of oedema were observed.
At the readings after 48 hours the number of animals with skin findings in the test group is appreciably higher than that in control group 1. However, as a result of evidently delayed reactions, the ratio of guinea pigs with skin changes to the number of animals used is in the same range in the control groups as in the test group at the readings after 72 hours.
Under the conditions of this study, the skin sensitising potential of the test material is inconclusive due to the high percentage of control animals that exhibit the same reactions as the test animals.

 

Skin Sensitisation: Grundler (1984) 

The skin sensitising potential of the test material was investigated using the Open Epicutaneous Test (OET). The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

The test material concentration selected for the induction and challenge tests were 50, 15, 5 and 1.5 %. During the induction, skin changes only occurred at the two highest concentrations of test material formulation (50 and 15 %) after several applications and did not show an appreciable increase in intensity during the four-week treatment period. After the two challenges, scarcely any qualitative or quantitative differences were found between the control and test groups. Test reactions were observed in very isolated cases at the 5 % challenge and in both pre-treated and non-pretreated animals at higher concentrations, therefore it can be concluded that the test material does not exhibit sensitising potential in the OET.

Under the conditions of this study, the test material was found to have no skin sensitising effect.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin sensitisation.