Registration Dossier

Administrative data

Description of key information

This substance is corrosive to skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June, 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-conducted study done according to guideline in force at the time. Documentation is sufficient but not extensive, also as was practice when the study was done. Study was performed prior to GLP regulations.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Application time was 24 hours instead of four.
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Remarks:
Application time was 24 hours which is permitted in this guideline.
GLP compliance:
no
Remarks:
Study was performed prior to GLP regulations.
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: Six rabbits treated on intact skin, six on abraded skin.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
72 hours after application
Number of animals:
Twelve (six intact skin, six abraded skin)
Details on study design:
Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.

Twelve healthy adult New Zealand White albino rabbits are used for 1-4 test substances. Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions.

An amount of 0.5 ml (in case of liquids) or 0.5 g (in case of solids or semi-solids) of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.

Six rabbits are treated on the intact skin, the other six on the abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.

After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol 84 (1944) 377-390). A second reading is made 48 hours later (72 hours after application).
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
6.8
Max. score:
7
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: see table below
Remarks:
see table below
Irritant / corrosive response data:
The individual and average skin irritation scores are presented in the table below. Generally, the dermal effect of TMPH after 24 hours was distinct ischemia and slight or moderate edema.
Other effects:
None recorded.

sa

 Rabbit number

Intact skin

24 hours

Intact skin

72 hours

Rabbit number

Abraded skin

24 hours

Abraded skin

72 hours

  erythema - edema   erythema - edema
 6609  4 - 2  4  6603  4 - 3  4
 6610  4 - 3  4 6604   4 - 3  3
 6611  4 - 3  4 6605   4 - 3  4
 6612  4 - 3  4 6606   4 - 3  4
 6613  4 - 3  4  6607  4 - 3  4
 6614  4 - 3  4  6608  4 - 2  4
 average  6.8  4.0    6.8  3.8
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize
Conclusions:
The following degree of skin irritation was observed. TMPH: very severe.
Executive summary:

Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.

Six rabbits are treated on the intact skin, the other six on the abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.

After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol 84 (1944) 377-390). A second reading is made 48 hours later (72 hours after application).

The following degree of skin irritation was observed. TMPH: very severe. Generally, the dermal effect of TMPH after 24 hours was distinct ischemia and slight or moderate edema.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-conducted study done according to guideline in force at the time. Documentation is sufficient but not extensive, also as was practice when the study was done. Study was performed prior to GLP regulations.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Remarks:
Study was performed prior to GLP regulations
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
None
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml of test material as supplied
Duration of treatment / exposure:
Eyelids were held shut for at least one second
Observation period (in vivo):
Seven days
Number of animals or in vitro replicates:
One
Details on study design:
In general the techniques of tests as published by the FDA of the United States (Fed. Reg 28 (119), 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 71 (1952) 36) are followed.

Six New Zealand White albino rabbits are used for each test substance. The animals are caged individually and receive no hay or other extraneous material that might enter the eyes. The eyes of the animals are examined before testing and only those animals without observable eye defects are used. One tenth of a milliliter of the test substance, or in case of solids or semi-solids, 100 milligrams of the test substance, is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye, remaining untreated, serves as a control. The eyes are not washed following instillation and the animals are released immediately. The eyes are examined at 24, 48, 72 hour and 7 days after instillation of the test material.

An animal is considered as giving a positive reaction if there is, at any of the readings, discernable opacity of the cornea (other than a slight dulling of the normal luster), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernable. The FDA-scoring scale is used. The test is considered positive is four or more of the animals in the test group of six rabbits exhibit a positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative. If two or three animals exhibit a positive reaction, the test is repeated, using a different group of six animals. The second test is considered as positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test is again repeated with a different group of six animals. Should a third test be needed, the substance will be regarded as an irritant if two or more animals exhibit a positive response.

Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eye are examined in a dark room under ultraviolet illumination. A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.

Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 48 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Time point:
other: 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 48 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 7 days
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 48 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 72 hours
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 7 days
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 48 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 72 hours
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 7 days
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Because of the severity of the ocular lesions caused by TMPH, this substance was examined in only one rabbit instead of six. The ocular effects were as follows: moderate to severe corneal opacity, slight iritis, moderate redness of the conjunctivae and swelling with lids about half closed. No recovery was observed during seven days after treatment.
Other effects:
None reported

See table above.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The present eye irritation test showed TMPH to be a very severe eye irritant.
Executive summary:

TMPH was examined for its primary skin and eye irritating properties.  Because of the severity of the ocular lesions caused by TMPH, this substance was examined in only one rabbit instead of six. The ocular effects were as follows: moderate to severe corneal opacity, slight iritis, moderate redness of the conjunctivae and swelling with lids about half closed. No recovery was observed during seven days after treatment. TMPH, tested in one eye, appeared to be a very severe eye irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on data from the skin and eye irritation studies, the product is classified as a category 1B (H314) skin irritant and as a category 1 (H318) eye irritant under EU CLP.