mancozeb (ISO); manganese ethylenebis(dithiocarbamate) (polymeric) complex with zinc salt  

Endpoint summary

Description of key information

The substance was tested for skin irritation in rabbits in a study according to OECD TG 404. No skin irritation was observed in any of the three male rabbits. The substance can thus be regarded as non-irritant to the skin.

The substance was tested for eye irritation in rabbits in a study following OECD TG 405. The substance was slightly irritant to the rabbit eye but classification for eye irritation under the CLP Regulation is not required.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-11-04 to 1997-11-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17th July 1992

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sarabhai Research Centre, Wadi Wadi, Baroda-390 007
- Weight at study initiation: 1.62 to 2.25 kg
- Housing: Individual in stainless steel wire meshed cage
- Diet: Rabbit pellet feed (Amrut brand) ad libitum (MF: Nav Maharashtra Chakan Oil Mills Limited, 43, Shaniwar Peth, Pune-411 030, Maharashtra, India)
- Water: Pure drinking water filtered through Aquaguard water filter system ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 22 ± 1.1 and 24 ± 1.8
- Humidity (%): 79 ± 8.9
- Air changes (per hr): 13 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

not specified

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

Skin changes such as erythema and edema were scored at 0, 1, 24, 48 and 72 hours after the removal of the test item.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: ca. 6 cm²
- Type of wrap if used: gauze patch secured with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: residual test item was removed with wet cotton
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
0, 1, 24, 48 and 72 hours after the removal of the test item.

SCORING SYSTEM:
- Method of calculation: Draize scoring

Irritation parameter:

erythema score

Basis:

animal: #1 - #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal: #1 - #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was determined not to be irritating to the skin.

Executive summary:

This study was performed to assess the acute dermal irritation potential of the test item to the rabbit. The method followed was as per the Organisation for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals No. 404 (adopted 17th July 1992) "Acute Dermal Irritation".

A single dose of 500 mg test item was moistened with distilled water and applied to intact skin of three male rabbits and kept in place for 4 hours, after which the test substance was removed with wet cotton. Observations were recorded at 1, 24, 48 and 72 h after removal of patch, using the Draize method to score dermal irritation. The treated skin sites in all animals appeared normal at one hour after patch removal.

The primary irritation index (PII) observed was 0 at 1, 24, 48 and 72 hour observation. Thus, the test item is classified as non-irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-11 to 1998-02-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24th February 1987

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Sarabhai Research Centre, Wadi Wadi, Baroda - 390 007
- Age at study initiation: 5 months old at the time of test substance instillation
- Weight at study initiation: 1.56 to 1.91 kg
- Housing: Individual in stainless steel wire meshed cage (45 cm breadth x 60 cm length x 45 cm height)
- Diet: Rat pellet feed (Amrut brand) ad libitum (MF: Nav Maharashtra Chakan Oil Mills Limited, 43, Shaniwar Peth, Pune-411 030, Maharashtra, India)
- Water: Pure drinking water filtered through Aquaguard water filter system ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 18 and 21
- Humidity (%): 64
- Air changes (per hr): 20 - 25
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

Half a minute after instillation the treated eyes of the three rabbits were washed with distilled water for half a minute using a volume and velocity of flow which did not cause injury.

Observation period (in vivo):

Readings of ocular lesions were made at 1 hour, 24 hours, 48 hours and 72 hours after the treatment.

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: washing with water
- Time after start of exposure: 0.5 minute

SCORING SYSTEM: in accordance with scoring system according to OECD 405

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test item is slightly irritant to the rabbit eye, but classification according to CLP Regulation is not required.

Executive summary:

This study was performed to assess the acute eye irritation potential of the test item in rabbits. The methods followed were as per the Organization for Economic Co-operation and Development (OECD) for testing of chemicals no. 405 (adopted 24th February, 1987) "Acute Eye Irritation"

Three healthy, adult male albino rabbits of New Zealand white strain, were selected for the study. An amount of 100 mg of the test item was instilled into an eye of each rabbit and the contralateral eye served as the control. Half a minute after instillation eye of all rabbits were washed with distilled water for half a minute using a volume and velocity of flow which did not cause injury. Observations were made following the method provided by the guidelines of the Organization for Economic Cooperation and Development (OECD) for testing of chemicals no. 405 (adopted 24th February 1987) "Acute Eye Irritation", at 1 hour (day 0), 24, 48 and 72 hours after instillation. The ocular reactions consisted of redness and chemosis. Redness was observed in all animals 1 hour after treatment and in 2 out of 3 animals at 24 and 48 hours. Chemosis was only noticed in 2 out of 3 animals at 1 and 24 hours. At 72 hours after treatment, all treated eyes were normal. In addition, no clinical toxic signs other than ocular were observed. Under the conditions of this study the test item is slightly irritant to the rabbit eye, but classification according to CLP Regulation is not required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

This study was performed to assess the acute dermal irritation potential of the test item to the rabbit. The method followed was as per the Organisation for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals No. 404 (adopted 17th July 1992) "Acute Dermal Irritation".

A single dose of 500 mg test item was moistened with distilled water and applied to intact skin of three male rabbits and kept in place for 4 hours, after which the test substance was removed with wet cotton. Observations were recorded at 1, 24, 48 and 72 h after removal of patch, using the Draize method to score dermal irritation. The treated skin sites in all animals appeared normal at one hour after patch removal.

The primary irritation index (PII) observed was 0 at 1, 24, 48 and 72 hour observation. Thus, the test item is classified as non-irritant to rabbit skin.

Eye Irritation:

This study was performed to assess the acute eye irritation potential of the test item in rabbits. The methods followed were as per the Organization for Economic Co-operation and Development (OECD) for testing of chemicals no. 405 (adopted 24th February, 1987) "Acute Eye Irritation"

Three healthy, adult male albino rabbits of New Zealand white strain, were selected for the study. An amount of 100 mg of the test item was instilled into an eye of each rabbit and the contralateral eye served as the control. Half a minute after instillation eye of all rabbits were washed with distilled water for half a minute using a volume and velocity of flow which did not cause injury. Observations were made following the method provided by the guidelines of the Organization for Economic Cooperation and Development (OECD) for testing of chemicals no. 405 (adopted 24th February 1987) "Acute Eye Irritation", at 1 hour (day 0), 24, 48 and 72 hours after instillation. The ocular reactions consisted of redness and chemosis. Redness was observed in all animals 1 hour after treatment and in 2 out of 3 animals at 24 and 48 hours. Chemosis was only noticed in 2 out of 3 animals at 1 and 24 hours. At 72 hours after treatment, all treated eyes were normal. In addition, no clinical toxic signs other than ocular were observed. Under the conditions of this study the test item is slightly irritant to the rabbit eye, but classification according to CLP Regulation is not required.

Justification for classification or non-classification

The following conclusion is taken from theRenewal Assessment Report prepared according to the Commission Regulation (EU) N° 1107/2009, Volume 3 - B.6 (AS), Dec 2018, of Mancozeb:

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The original DAR (2000) describes four skin irritation studies in the rabbit. The results of these studies show that the test item is not irritant to rabbit skin. The skin irritation study (Tiwari, 1997) confirms that the test item is not irritant to rabbit skin. No classification for skin irritation under the CLP Regulation is required.

The original DAR (2000) describes six eye irritation studies in the rabbit. The results of these studies indicate that the test item does have some potential to irritate the eye of rabbits. In the original DAR (2000) the test item was classified as an eye irritant. However, in a more recent assessment (Review Report, SANCO/4058/2001-rev. 4.4 July 2009) the test item was defined as "slightly irritant, no classification needed". The latter conclusion was mainly based on those studies in the original DAR (2000) in which the eyes were rinsed 1 hour after treatment (as recommended by the updated OECD TG 405 (2012)). In these studies, irritation of the eye was insufficient for classification. The eye irritation study (Tiwari, 1998) (which employed rinsing) confirms that the test item is slightly irritant to the rabbit eye, but that no classification for eye irritation under the CLP Regulation is required.