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Diss Factsheets

Administrative data

Description of key information

The substance is sensitising to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 406 (Skin Sensitisation)
Version / remarks:
1992
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The guinea pig maximisation test has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Route:
intradermal
Vehicle:
water
Concentration / amount:
50 %
Day(s)/duration:
Day 0
Adequacy of induction:
other: selected based on preliminary study
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
0.2 mL of 50 % of test substance dilution
Day(s)/duration:
Day 7
Adequacy of induction:
other: Prior to application, local irritation had been created by painting the skin with 10% sodium lauryl sulphate
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.1 mL of the test substance
Day(s)/duration:
Day 20
No. of animals per dose:
20 test animals and 10 control animals
Details on study design:
The potential of Sanachem Mancozeb Technical to cause skin sensitisation was evaluated in guinea pigs using a Magnusson Kligman Maximisation Test. The study employed 30 male Dunkin-Hartley guinea pigs: 20 test with 10 controls. An area of dorsal skin from the scapular region (ca. 6 x 8 cm) of the animals was clipped free of hair ca. 24 hours prior to administration on Day 0 of three pairs of intradermal injections (0.1 mL/site) just within the boundaries of a 4 x 6 cm area in the clipped region.
The test group injections were:
(1) Freund’s complete adjuvant (FCA) 50:50 in physiological saline;
(2) The test substance, diluted with distilled water to the concentration selected in a preliminary study (50%);
(3) The test substance, diluted with a 50:50 mixture of FCA and physiological saline to the concentration selected in the preliminary study (50%).
The control group injections were:
(1) FCA 50:50 in physiological saline;
(2) Vehicle used in (2) for the test group (distilled water);
(3) FCA 50:50 in distilled water.
On Day 7 (after clipping the fur again 24 hours earlier), topical applications were made to the same site after local irritation had been created by painting the skin with 10% sodium lauryl sulphate. The test group received 0.2 mL of a 50% dilution of the test substance in distilled water on filter paper. The control group were treated with distilled water. The patches were held in place under surgical adhesive tape and this was further secured with a double layer of semi-occlusive dressing. The patches remained in place for 48 hours.
On Day 20, the flanks of treated and control animals were cleared of hair and on Day 21, patches loaded with 0.1 mL of the test substance were applied to one flank. The patches were held in place for 24 hours with an occlusive dressing. Approximately 21 hours after removing the patch, the challenge area was cleaned and closely clipped and depilated if necessary. The skin reaction to the challenge application was observed at 48 and 72 hours after the start of the challenge and graded for erythema.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
discrete to patchy erythema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
discrete to patchy erythema
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10

None of the control animals reacted positively to the dermal challenge. However, four animals of the test group showed discrete to patchy erythema after the topical induction period, and seven animals reacted in a similar way during the topical challenge, both after 24 and 48 hours. The exposed skin areas of both the control and challenge groups were dry and peeling after exposure.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The test substance was found to be skin sensitizing in this in vivio study.
Executive summary:

The potential of the test substance to cause skin sensitisation was evaluated in guinea pigs using a Magnusson Kligman Maximisation Test. The study employed 30 male Dunkin-Hartley guinea pigs: 20 test with 10 controls. An area of dorsal skin from the scapular region (ca. 6 x 8 cm) of the animals was clipped free of hair ca. 24 hours prior to administration on Day 0 of three pairs of intradermal injections (0.1 mL/site) just within the boundaries of a 4 x 6 cm area in the clipped region.

The test group injections were:

(1) Freund’s complete adjuvant (FCA) 50:50 in physiological saline;

(2) The test substance, diluted with distilled water to the concentration selected in a preliminary study (50%);

(3) The test substance, diluted with a 50:50 mixture of FCA and physiological saline to the concentration selected in the preliminary study (50%).

 

The control group injections were:

(1) FCA 50:50 in physiological saline;

(2) Vehicle used in (2) for the test group (distilled water);

(3) FCA 50:50 in distilled water.

On Day 7 (after clipping the fur again 24 hours earlier), topical applications were made to the same site after local irritation had been created by painting the skin with 10% sodium lauryl sulphate. The test group received 0.2 mL of a 50% dilution of the test substance in distilled water on filter paper. The control group were treated with distilled water. The patches were held in place under surgical adhesive tape and this was further secured with a double layer of semi-occlusive dressing. The patches remained in place for 48 hours.

On Day 20, the flanks of treated and control animals were cleared of hair and on Day 21, patches loaded with 0.1 mL of the test substance were applied to one flank. The patches were held in place for 24 hours with an occlusive dressing. Approximately 21 hours after removing the patch, the challenge area was cleaned and closely clipped and depilated if necessary. The skin reaction to the challenge application was observed at 48 and 72 hours after the start of the challenge and graded for erythema.

None of the control animals reacted positively to the dermal challenge. However, four animals of the test group showed discrete to patchy erythema after the topical induction period, and seven animals reacted in a similar way during the topical challenge, both after 24 and 48 hours. The exposed skin areas of both the control and challenge groups were dry and peeling after exposure.

Under the conditions of this study, the test substance induced a positive response in 35% of the test animals (7/20) and is concluded to be a skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The following summary is taken from the CLH report (Dec 2017) of Mancozeb.


 


The original DAR (2000) under Directive 91/414 describes two Buehler tests (Anonymous, 1988; Anonymous, 1986) conducted in guinea-pigs and three guinea-pig maximisation studies (Matshushita et al., 1976; Anonymous, 1994; Anonymous, 1997). The results of the majority of these studies (Anonymous., 1986; Matshushita et al., 1976; Anonymous, 1994c) show that mancozeb is a skin sensitiser. Since then, another skin sensitisation study (Anonymous, 2007) has become available. This study conformed to GLP and OECD test guideline 406. Mancozeb (88.6% pure) was tested in male guinea pigs according to the Buehler method. Mancozeb was negative in this study. However, it is noted that the Buehler method is less sensitive than the M+K method. Overall, therefore, the results of this study are not inconsistent with the studies in the original DAR (2000) under Directive 91/414.


In the Buehler assay by Anonymous (1988), grade 1 erythema was noted in 1/20 mancozeb-treated animals 48 hours after challenge, and in 1/20 mancozeb-treated animals 24 hours after re-challenge. However, this was not the same animal that exhibited erythema during the challenge phase. Appropriate responses were seen with positive and sham controls. In this study mancozeb did not induce a positive response.


In the second Buehler study (Anonymous, 1986) 2/10 animals had slight to well-defined erythema with or without slight or well-defined oedema at 24 and 48 hours following challenge with 50% mancozeb. Similar reactions were not seen in negative control animals; therefore it was concluded that under the test conditions mancozeb is a skin sensitiser.


Guinea pig maximisation studies were conducted by Anonymous (1994) and Anonymous (1997a). In the study by Anonymous (1994) none of the control animals reacted positively to the dermal challenge. However, seven animals of the test group showed discrete to patchy erythema during the topical challenge, after both 24 and 48 hours. As 35% (7/20) of animals gave a positive response in this adjuvant test it is concluded that a skin sensitising potential was demonstrated under the conditions of this study.


In the second guinea pig maximisation test conducted by Anonymous (1997a) 3/20 animals exhibited grade 1 erythema at both 24 and 48 hours following challenge. As a 15% positive response was observed in this second adjuvant test it was concluded that mancozeb was not a skin sensitiser under the conditions of this study.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The following conclusion is taken from the CLH report (Dec 2017) of Mancozeb.


On the basis of the positive results obtained in 3 out of the 6 available studies, the current classification of mancozeb for skin sensitisation in category 1 (H317) is confirmed.