Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 15, 2016 - March 10, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Exception to guideline 404, for not testing weight of evidence analysis by the test facility.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide

EC Number:

946-272-2

Molecular formula:

Not specified (UVCB substance).Molecular formula of the main substance:C14Cu2H25Na1O17

IUPAC Name:

Reaction products of sodium glucoheptonate with copper sulfate and ammonium hydroxide

Test material form:

solid: granular

Remarks:

microgranulated

Details on test material:

- Name of test material (as cited in study report): DABQUEL COMPLEX CuP
- Substance type: complex
- Physical state: dark green microgranulated
- Composition of test material, percentage of components:
Copper complexed content: 12.5%
Total Copper content: 12.9%
- Lot/batch No.: 4146S0616
- Expiration date of the lot/batch: June 16, 2016
- Storage condition of test material:
Storage Temperature: Room temperature
Storage Container: Keep container tightly closed in a dry, cool and well ventilated place
Storage Location : Test Item Control Office, JRF

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sainath Agencies, Hyderabad, India
- Age at study initiation: 4 to 5 months
- Weight at study initiation: Minimum: 2.406, Maximum: 2.560
- Housing: individually in stainless steel wire meshed cages were used.
- Diet (e.g. ad libitum): Teklad certified Global High Fiber Rabbit pellet Feed manufactured by Harlan, USA ad libitum
- Water (e.g. ad libitum): UV sterilised drinking water filtered through Kent Reverse Osmosis water filtration system ad libitum
- Acclimation period: 6 to 8 days

Animal Identification
Each rabbit was uniquely numbered on the ear using a tattoo machine. Appropriate labels were attached to the cages indicating the study number, test item code, sex, dose, type of study, cage number and animal number.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 °C
- Humidity (%): 63 to 65%
- Air changes (per hr): minimum 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h artificial light and 12 h darkness, light hours being 06:00 - 18:00 h

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
- Concentration (if solution): 1 %

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions of each rabbit were observed at 1, 24, 48 and 72 h post patch removal.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: gauze patch that was secured at the margins by non-irritating tape for a period of 4 h

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 4 h exposure period, the residual test item was removed with cotton soaked in distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Irritation was scored according to OECD 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24

Score:

0

Reversibility:

other: not applicable

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48

Score:

0

Reversibility:

other: not applicable

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72

Score:

0

Reversibility:

other: not applicable

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24

Score:

0

Reversibility:

other: not applicable

Results 5

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48

Score:

0

Reversibility:

other: not applicable

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72

Score:

0

Reversibility:

other: not applicable

Results 7

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Irritant / corrosive response data:

There were no signs of systemic adverse effect in any treated rabbits.
Erythema was evident at 1 h in all rabbits which resolved by 24 h post patch removal in all rabbits. The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for individual animals were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively.

Any other information on results incl. tables

Mean Dermal Irritation Score

The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for animal Nº 1, 2 and 3 were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively (TABLE 2).

Narrative Description of Skin Reactions

Following the 4 h exposure period (day 0), the skin of each rabbit was observed at 1, 24, 48 and 72 h post patch removal.

At 1 h post patch removal, the treated skin site revealed very slight erythema (barely perceptible) in all three rabbits (TABLE 1).

At 24 h post patch TIA, the treated skin site recovered completely and appeared normal in all three rabbits throughout the experimental period (TABLE 1).

The control skin sites of all three rabbits were normal with no erythema and no oedema observed throughout the experimental period (TABLE 1).

Clinical Observations other than Dermal Irritation

No clinical signs were observed in any rabbit throughout the experimental period (TABLE 2).

Interpretation of Results

The mean scores of erythema (0.00) and oedema (0.00) observed at the 24, 48 and 72 h post patch removal observation time-points indicated that the DABQUEL COMPLEX CuP is a non-irritant under the described experimental conditions.

Acute Dermal Irritation Study of DABQUEL COMPLEX CuP in Rabbits

TABLE1: Dermal Irritation Scores 

Control Site: Untreated                                                                                                    Sex: Male

Rabbit N°	Site of Application	Observations after Patch Removal
		Erythema				Oedema
		Hour				Hour
		1	24	48	72	1	24	48	72
1	Right	0	0	0	0	0	0	0	0
2	Right	0	0	0	0	0	0	0	0
3	Left	0	0	0	0	0	0	0	0

 

Treated Site: 500 mg DABQUEL COMPLEX CuP (pulverised and moistened with 0.5 mL distilled water)

Rabbit N°	Site of Application	Observations after Patch Removal
		Erythema				Oedema
		Hour	Hour
		1	24	48	72	1	24	48	72
1	Left	1	0	0	0	0	0	0	0
2	Left	1	0	0	0	0	0	0	0
3	Right	1	0	0	0	0	0	0	0

Note: Refer section 2.12 for Irritation Scores

Acute Dermal Irritation Study of DABQUEL COMPLEX CuP in Rabbits

Table 2: Clinical Observations and Body Weight (kg) of Individual Rabbit

Sex: Male

Rabbit N°	Clinical Observations made on Day				Body Weights (kg)
	0	1	2	3	Before Treatment	At Termination
1	1	1	1	1	2.426	2.515
2	1	1	1	1	2.406	2.531
3	1	1	1	1	2.560	2.651

Key:               0 = Day of dermal application

Clinical Sign:  1 = Normal

Applicant's summary and conclusion

Interpretation of results:

not irritating

Conclusions:

Based on the results of this study, and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS 2015), DABQUEL COMPLEX CuP is not classified as a skin irritant

Executive summary:

In an acute dermal irritation study, three adult male New Zealand White rabbits were dermally exposed to 500 mg DABQUEL COMPLEX CuP (pulverised and moistened with 0.5 mL distilled water), for 4 h (day 0), applied to approximately 6 cm² area of skin. Initially one rabbit was tested with a single patch applied evenly to the intact skin for a period of 4 h. Based on the observations at 24 h post patch removal, two additional rabbits were tested simultaneously to confirm the irritation response. The control skin site of each rabbit was untreated. The treated and the control sites were covered with a gauze patch that was secured at the margins by non-irritating tape for a period of 4 h. At the end of the 4 h exposure period, the residual test item was removed with cotton soaked in distilled water. The skin reactions of each rabbit were observed at 1, 24, 48 and 72 h post patch removal. Irritation was scored according to OECD 404.

There were no signs of systemic adverse effect in any treated rabbits.

Erythema was evident at 1 h in all rabbits which resolved by 24 h post patch removal in all rabbits. The mean dermal irritation scores at 24, 48 and 72 h post-patch removal for individual animals were 0.00, 0.00, 0.00 for erythema and 0.00, 0.00, 0.00 for oedema, respectively.

Based on the results of this study, an indication of the classification for DABQUEL COMPLEX CuP is as follows:

Globally Harmonized System of Classification and Labeling of Chemicals (GHS 2015): Not classified as a skin irritant