Registration Dossier

Administrative data

Description of key information

Skin corrosion: corrosive, based on weight of evidence from studies summarized in the EU RAR 2005 report

Eye irritation:  corrosive,  non-standard study, outcome sufficently documented

Respiratory irritation: no data, based on manufacture's experience

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:
6-22 March 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: FDA guideline 1500.41 in Federal Register 38, no. 187, 27-09-1973, p 27019
Principles of method if other than guideline:
Examination of skin irritation in rabbits, see further below
GLP compliance:
no
Remarks:
did not exist at that time
Specific details on test material used for the study:
crystalline flakes dissolved in physiological saline
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
Strain: Hoe:HIMK (SPFWiga) - own breed
Body weight: 1.5-2.5 kg
Standard feed: ERKA 8300
Food and water ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: intact shaved and abraded skin
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
first test: 500 mg pasted with 0.05 ml vehicle
second test: 100 mg/kg as 50% solution in vehicle
Duration of treatment / exposure:
24 h
Observation period:
24, 48 and 72 h
Number of animals:
6 per group
Details on study design:
2.5 cm2 application area

Irritation parameter:
other: Irritation index
Basis:
mean
Time point:
other: 24 and 72 h
Score:
4.8
Max. score:
8
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
In this older study other scoring criteria have been used
Irritant / corrosive response data:
first test: all animals died within 24 h; skin was hard and black-green discoloured. A section of the skin showed a clear 'liver lobe drawing'. The subcutaneous tissue in the area of ​​the treatment sites was without abnormalities.

second test:
- at 24 h: very strong erythema and edema. The skin was grey-green discoloured, at the edges it was cracked and a colourless fluid was secreted.
- at 48 h: clear reduction of erythema and edema; detachment of discoloured and corroded skin started
- at 72 h: the skin of all animals was indurated, bulged, parchment-like, deeply cracked and showed large-area skin detachment. In 5 rabbits open wounds with colourless (3) or reddish coloured (2) secretion were observed.
Other effects:
not reported

For both erythema and oedema a maximum score of 4 was used.

The final score (Irritation index) for every animal was obtained by adding the score of erythema and edema for both intact and abraded skin at 24 and 72 h. The sum of all animals was taken and divded by the number of animals and a factor 4.

The classification was as follows:

0.0 -0.5 = non irritant

0.6 -3.0 = slightly irritating

3.1 -5.0 = moderately irritating

5.1 -8.0 = severely irritating

In this study the irritation index was 4.8, and thus moderately irritating. However, there was an etching effect and as such MCA should be considered as strongly irritating/corrosive.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
In this study the irritation index was 4.8 (maximum is 8), and thus moderately irritating. However, there was an etching effect and as such MCA should be considered as strongly irritating/corrosive.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

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:
6-22 March 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: FDA guideline: federal register 38, no. 187, 27-09-1973, p 27019
Deviations:
not specified
GLP compliance:
no
Remarks:
did not exist at that time
Specific details on test material used for the study:
crystalline flakes dissolved in physiological saline
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hoechst Aktiengesellschaft (breeding at the same laboratory)
- Weight at study initiation: 1.5-2.5 kg
- Housing: single housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES: From: 06-March 1979 To: 22-March 1979
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
100 mg pasted with 0.01 mL vehicle
Duration of treatment / exposure:
Single application in one eye; the other one functioned as control
Observation period (in vivo):
1, 7, 24, 48, and 72 h (however, due to welfare reasons animals were sacrificed at 24h)
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with physiological saline.
- Time after start of exposure: 24h after treatment

SCORING SYSTEM: Appraisal of the safety of chemicals in foods, drugs and cosmetics, FDA, Austin , Texas, p. 51, 1975

The 48-h and 72-h observation was done after installation of a drop of Na-fluoroescien (0.01%).
Irritation parameter:
other: Irritation index
Basis:
mean
Time point:
24 h
Score:
106
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: severe eye irration; animals were sacrificed after 24 h, no individual scores were given
Remarks:
In this older study other scoring criteria have been used
Irritant / corrosive response data:
Highest irritation index of 106 was observed at 7 and 24 h- mucous membrane was grey discoloured and corrosive.
Because of animal welfare reasons the study was terminated at 24 h.
Other effects:
Not reported
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Severely damaging to the eyes. Animals were sacrificed at 24 h due to welfare reasons.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

A key study for skin irritation / corrosion is available, together with weight of evidence from studies summarized in the EU RAR (2005) report it is concluded that the substance is corrosive to the skin. This is in line with expectations based on the chemical properties of the substance (strongly acidic).

The key study for eye irriation is not a standard test, but the outcome is sufficiently documented to accept "casues irreversible damage" as the outcome.

No data are available for respiratory irritation but experience from manufacturing sites indicates that irritating MCA vapours can be released when heated. Acoording to ECB (EU RAR, 2005): Respiratory irritation was observed at 23.7 mg/m3 in rats. The threshold for respiratory (sensory) irritation in humans was reported to be 5.7 mg/m3.


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 available animal data and experience in humans MCA should be classified as corrosive to skin and eyes.

Vapours from heated MCA have shown to be irritating to the respiratory tract.