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Diss Factsheets

Administrative data

Description of key information

No study available.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, according to GPL..
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
other: not applicable
Strain:
other: not applicable
Details on test animals or test system and environmental conditions:
Not applicable
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
50 µl applied to each tissue.
Duration of treatment / exposure:
- 3 min
or
- 60 min
Number of animals:
Not applicable
Irritation / corrosion parameter:
other: other: Tissue viability (%)
Value:
17
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 3 minutes. (migrated information)
Irritation / corrosion parameter:
other: other: Tissue viability (%)
Value:
4.7
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 1 hour. (migrated information)
Irritant / corrosive response data:
- Reduction of MTT by test substance:
After the one hour incubation, the MTT solution control (orange/red) remained unchanged. The initial colour of the test substance, Monochloramine/MTT mixture was red and then purple/red with purple colour on the bottom of the well after the one hour incubation indicating the test substance had reduced the MTT. As the test substance had reduced the MTT, freeze killed tissues (which have no metabolic activity but absorb and bind the test substance like viable tissues) were included in the assay together with the live tissues as a control.

- Check for colouring potential of test substance:
The test substance, Monochloramine/water solution and water control were colourless after the 15 minute shaking period. Therefore, the test substance had not shown any potential for colouring water.

The results after the treatment with the test substance are summarised in the following table:

Sample

Tissue viability as % of mean negative control value

Prediction

3 minute contact

1 hour contact

Replicate

Mean±SD

Replicate

Mean±SD

Negative Control (purified water)

97.1

100.0 ± 4.038 CV = 0.0

93.9

100.0 ± 8.589 CV = 0.086

Not applicable

102.9

106.1

Monochloramine

8.3

17.0 ± 12.223

CV Not applicable

5.2

4.7 ± 0.782

CV Not applicable

Corrosive, sub-category 1

25.6

4.1

Positive control

(8.0 N KOH)

11.7

12.3 ± 0.942 CV Not applicable

2.1

1.9 ± 0.269 CV Not applicable

Corrosive, sub-category 1

13.0

1.7

SD = Standard Deviation                 CV = Coefficient of Variation

The negative control:

The mean optical density of each duplicate negative control value for the three minute and one hour contact were 1.686 and 1.612, respectively. Both values were between the acceptance range of ≥0.8 to ≤2.8.

The positive control:

The mean relative tissue viability of the positive control, 8.0 N potassium hydroxide, for the one hour application was 1.9%. This value was below the maximum acceptable value of 15%.

 Inter-tissue viability difference:

The coefficient of variation (CV) was not applicable for the test substance, Monochloramine, and positive control three minute and one hour applications, as the mean percentage viability was below the 20% - 100 % viability range. All other values did not exceed the CV value of 0.3.

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions of this study, test substance is considered to be corrosive to skin (sub-category 1).
Executive summary:

The objective of this test was to assess the skin corrosivity,in vitro, of the test substance, Monochloramine (solution of 1 % ).

The test substance was applied for three minutes and one hour to the EpiDerm™ three-dimensional human skin model. The model consisted of normal, human-derived epidermal keratinocytes, which had been cultured on 0.6 cm2 inserts to form a multilayered, highly differentiated model of the human epidermis with a functional multilayered stratum corneum. The cell viability of the multi layers was determined by mitochondrial dehydrogenase activity assessed by the reduction of MTT (3‑(4,5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide) to a soluble, coloured, formazan product. The formazan produced was quantified by spectrophotometric measurement. The prediction model uses the percentage viability values (compared to negative control viability) at three minute and one hour exposure times to identify corrosive and non-corrosive substances. 

 

The test substance, Monochloramine, elicited a mean tissue viability of 17.0% for three minute contact and 4.7% for one hour contact and was predicted as corrosive, sub-category 1, in the EpiDerm™ skin corrosivity test.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin and eye corrosion/irritation assessment:

No in vivo experimental data are available for skin and eye corrosion/irritation endpoints. A sequential testing strategy was applied in order to evaluate the skin corrosivity/ irritancy potential of the solution of Monochloramine solution from 0.25 to 1 %. First, the physicochemical properties were taken into consideration to evaluate the skin and eye corrosivity/ irritancy potential of this substance. Due to the extreme pH (pH = 12.5) of the solution of monochloramine from 0.25 to 1 % (2.5 to 10 g/l) and due to the lack of in vivo experimental data, a corrosive classification is expected. To confirm this classification, an alkaline reserve test and an in vitro skin corrosion using a human skin model were performed. The free alkalinity was determined to be 0.0914 (%mass/mass) with a pH of 13.36. Classification based on the pH-alkali reserve indicates that the substance should be classified as Irritant. Nevertheless, in the EpiDermTMskin corrosivity test, the test substance, Monochloramine (1 % solution), elicited a mean tissue viability of 17 % for three minute contact and 4.7 % for one hour contact and was predicted as corrosive, sub-category 1. Therefore, the corrosive classification of Monochloramine (1 % solution) is confirmed and maintained.

The solution of Monochloramine below or equal at 0.0003 % (3 mg/l) was also considered to evaluate its skin and eye corrosivity/ irritancy potential since workers may also be exposed at concentrations below 0.0003 % (3 mg/l). At concentrations below or equal 0.0003 % (3 mg/l), the pH of the solution is around 8. Therefore, the corrosive classification due to the extreme pH should not be applied. In addition, in the United States, Monchloramine is used to provide disinfection residual in drinking-water distribution systems where it is difficult to maintain free chlorine residual or where the formation of disinfection by-products is a problem. Levels up to 4 mg/l are typically added and decrease with length of residence to around 0.6 mg/l. The WHO (1998) has established a drinking-water guideline for monochloramine of 3 mg/l. Australia and New Zealand have also established a guideline of 3 mg/l for monochloramine (National Health and Medical Research Council and Agriculture and Resource Management council of australia and New zealand, 1996). In Canada, the maximum allowable concentration for total chloramines has been established at 3.0 mg/l (Health Canada, 2003). Based on the large uses in different countries of drinking-water containing monochloramine levels up to 3 mg/l, no classification is applied for concentrations below or equal at 0.0003 % (3 mg/l).

Respiratory irritation assessment:

Monochloramine belongs to the chloramine category that contains also dichloramine and trichloramine. Trichloramine, is recognized as a strong irritant and lacrimator. Gagnaire et al. (1994) evaluated the expiratory bradypnoea (indicative of upper airway irritation) in mice during a 60 min oronasal exposure to increasing concentrations of trichloramine. The airborn concentration resulting in a 50 % decrease in the respiratory rate of mice (RD50) was calculated for trichloramine. The RD50 value of trichloramine was 2.5 ppm (12.3 µg/ml) and the maximal response to trichloramine was reached in 10 minutes. In addition, it has been assumed that chloramines are responsible for the irritation experienced by swimming pool workers or by workers in a salad processing plant (Heri et al., 1994 and 1998). The presence of chloramines in swimming pool atmospheres is likely an account of the reaction between the chlorine-containing agents used for disinfecting the water and nitrogenous compounds introduced by humans. From questionnaires completed by the swimming pool instructors and measurements of the concentration of chloramine in the atmosphere, the irritation phenomena seemed to appear at chloramine values of around 0.5 mg/m3. In the green salad processing plant, using water containing chlorine or sodium hypochlorite, chlorine and hypochlorous acid coming into contact with the biological fluids from poultry processing lead to the formation of inorganic chloramines. In the case of vegetable processing industry, the source of the nitrogen compounds necessary for chloramine formation is probably the sap proteins released when cutting the vegetable. Results indicated that chloramine exposure in swimming pools is mainly composed of nitrogen trichloride although for vegetable processing facilities workers seemed mainly exposed to a mixture of mono- and dichloramine. Then, based on human exposures reported in the open scientific literature it can be assess that monochloramine, dichloramine and trichloamine are respiratory irritants.

Justification for selection of skin irritation / corrosion endpoint:

In an EpiDermTM skin corrosivity test, the test substance, Monochloramine (1 % solution), elicited a mean tissue viability of 17 % for three minute contact and 4.7 % for one hour contact and was predicted as corrosive, sub-category 1. Then, the in vitro result confirmed the corrosive classification predicted by the extreme pH (pH = 12.5) of the solution of monochloramine at 1 %.

Justification for selection of eye irritation endpoint:

Based on the EpiDerm TM skin corrosivity test result, the monochloramine (1 % solution) is expected to be also corrosive to eyes.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the worst case assumption, as there are no in vivo experimental data available, the monochloramine have to be classified as

Skin corrosion/irritation:

DSD C, R35: Causes severe burns; CLP Skin Corr. 1A, H314: Causes severe skin burns and eye damage (monochloramine solution from 2.5 to 10 g/l)

DSD: not classified; CLP: not classified (monochloramine < or = 3 mg/l)

Eye corrosion/irritation:

Implicit in classification as corrosive (monochloramine solution from 2.5 to 10 g/l)

DSD: not classified; CLP: not classified (monochloramine < or = 3 mg/l)

Respiratory irritation:

DSD Xi; R37: Irritating to respiratory system; CLP/GHS STOT SE 3, H335: May cause respiratory irritation

DSD: not classified; CLP: not classified (monochloramine < or = 3 mg/l)