Tetramethylammonium hydrogen phthalate

Endpoint summary

Description of key information

Reliable studies for skin irritation and eye irritation are available, performed according to EC/ OECD guidelines and GLP principles. In both studies, test substance is only indicated by abbreviation; no information on test substance purity (both Klimisch 2). Studies performed with TMAP, which is the same test substance as TMHP (tetramethylammonium hydrogen phthalate). In the SNIF file of the test substance, summaries of two other studies are available. The data on eye irritation are used as supporting study (Klimisch 2). Due to lack of experimental data, the skin irritation study from the SNIF file was found to be not reliable (Klimisch 3). All available data are consistent: tetramethylammonium hydrogen phthalate does not show irritant effect on the skin, but is found to be irritant to the eye. 

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:

June 1987-July 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. Test substance only indicated by abbreviation; no information on test substance purity.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

yes

Remarks:

no information on test substance purity

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately twelve to sixteen weeks old
- Weight at study initiation: 2.70 - 2.88 kg
- Housing: individually in suspended metal cages.
- Diet: ad libitum (Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K.)
- Water: Free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 65 - 68
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 June 1987 To: 21 June 1987

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: moistened with water

Controls:

not required

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: gauze patch, secured with a strip of surgical adhesive tape (BLENDERM); the trunk of each rabbit was wrapped in an elasticated corset
(TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to Draize

Irritation parameter:

erythema score

Basis:

animal: #1,2,3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: mean score; one animal scored 1 at 1h after exposure

Irritation parameter:

edema score

Basis:

animal: #1,2,3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: mean score

Irritant / corrosive response data:

Very slight erythema was noted at one treated skin site one hour after removal of the patches. No adverse skin reactions were noted at the remaining treated skin sites at this time or at any treated skin site at subsequent 24, 48 and 72- hour observations.

Other effects:

No corrosive effects were noted.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a skin irritation test in rabbits performed according to OECD guideline 404 and GLP principles, TMAP was found to be not irritating to rabbit skin.

Executive summary:

A skin irritation test in rabbits was performed according to OECD guideline 404. Very slight erythema was noted at one treated skin site one hour after removal of the patches. No adverse skin reactions were noted at the remaining treated skin sites at this time or at any treated skin site at subsequent 24, 48 and 72- hour observations.

The test material produced a primary irritation index of 0.0 and was classified as non- irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

August 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. No information on test substance purity.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on purity

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no information on purity

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approximately 12 to 16 weeks old
- Weight at study initiation: 2.22 - 2.54 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum (RABMA Rabbit diet, Special Diet Services Ltd., Witham, Essex, U.K.)
- Water: free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 56-67
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 August 1993 To: 25 August 1993

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

100 mg

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Reversibility of any observed effect: changes fully reversible within 14 days.

Other effects:

Other ocular effecs noted were a dulling of the normal lustre of the corneal surface (2 animals, 1 hour after treatment), sloughing of the cornea (in one eye at the 24 hour observation) and petechial haemorrhage of the conjunctival or nictitating membranes (in one eye at the 24, 48 and 72 hour observations).

Interpretation of results:

other: cat. 2

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on an eye irritation test with TMAP according to OECD/EC guidelines and GLP principles, the test substance is found to be irritating to the eyes (classified cat 2).

Executive summary:

An eye irritation test with TMAP was performed according to OECD/ EC guidelines and GLP principles. The mean corneal opacity score at 24, 48 and 72 hours of three rabbits was found to be 1, 1 and 0. The mean iris score was <1 for all animals, mean conjunctival score was 2 for one rabbit and <2 for the other two. Mean chemosis score were <2 for all three rabbits. Other ocular effecs noted were a dulling of the normal lustre of the corneal surface (2 animals, 1 hour after treatment), sloughing of the cornea (in one eye at the 24 hour observation) and petechial haemorrhage of the conjunctival or nictitating membranes (in one eye at the 24, 48 and 72 hour observations). All effects were reversible within 14 days.

Since the corneal opacity was ≥ 1 in 2 of the three tested animals (mean 24, 48 and 72 hours), TMAP is regarded as irritant to the eye (classified cat 2).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A reliable skin irritation test in rabbits was performed according to OECD guideline 404. Very slight erythema was noted at one treated skin site one hour after removal of the patches. No adverse skin reactions were noted at the remaining treated skin sites at this time or at any treated skin site at subsequent 24, 48 and 72- hour observations.This result is confirmed in a non-reliable study.

An eye irritation test with TMAP was performed according to OECD/ EC guidelines and GLP principles. The mean corneal opacity score at 24, 48 and 72 hours of three rabbits was 1, 1 and 0. The mean iris score was <1 for all animals, mean conjunctival score was 2 for one rabbit and <2 for the other two. Mean chemosis score were <2 for all three rabbits. Other ocular effecs noted were a dulling of the normal lustre of the corneal surface (2 animals, 1 hour after treatment), sloughing of the cornea (in one eye at the 24 hour observation) and petechial haemorrhage of the conjunctival or nictitating membranes (in one eye at the 24, 48 and 72 hour observations). All effects were reversible within 14 days.

In the available SNIF file for tetramethylammonium hydrogen phthalate, an eye irritation test with TMAP is summarized, performed according to OECD/ EC guidelines and GLP principles. The mean corneal opacity score at 24, 48 and 72 hours of three rabbits was found to be 1, 1 and 0. The mean iris score was 0.5, 1 and 0, mean conjunctival score was 2 for two rabbits and 1 for the third. Mean chemosis scores were 1 for all three rabbits. Other ocular effects noted were a dulling of the normal lustre of the corneal surface, sloughing of the cornea and petechial haemorrhage of the conjunctival or nictitating membranes. All effects were reversible within 3 days.

It is of note that TMAP is the same test substance as TMHP (tetramethylammonium hydrogen phthalate).

Justification for selection of skin irritation / corrosion endpoint:
One reliable study is available.

Justification for selection of eye irritation endpoint:
There are 2 reliable studies available, a key study and a supporting study. The key study has been selected. Based on the results of both studies, the substance needs to be classified.

Effects on eye irritation: irritating

Justification for classification or non-classification

As in two reliable studies the corneal opacity was ≥ 1 in two of the three tested animals (mean 24, 48 and 72 hours) and in addition in one of these 2 studies also the mean conjunctival score was ≥ 2 in two of the three tested animals (mean 24, 48 and 72 hours), TMHP needs to be classified as irritating to the eyes (category 2) according to Regulation (EC) No 1272/2008.

Based on the available skin irritation studies with tetramethylammonium hydrogen phthalate, the substance does not need to be classified as irritating to skin according to Regulation (EC) No 1272/2008.

Based on the available studies, the substance does not need to be classified according to the DSD for skin and eye irritation.