Terephthalic acid

Endpoint summary

Description of key information

In vivo studies show that the substance is a mild skin and eye irritant but is not corrosive, and is not classified according to current criteria.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No information: study reported in 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Proprietary study, guideline comparable

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

: some of the application sites were abraded; 24-hour application, no scores for 1 hour or 48 h

GLP compliance:

no

Remarks:

: older study, pre-dates GLP

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

Albino rabbits.

Type of coverage:

occlusive

Preparation of test site:

other: abraded and intact

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

500 mg undiluted substance was applied

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Details on study design:

500 mg undiluted test substance was applied to the skin of 6 rabbits for 24 hours, and the test site was occluded. Each animal had two application sites; one that was abraded and one that remained intact.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hours

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects seen

Remarks on result:

other: Intact skin

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24h

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 72h

Remarks on result:

other: Abraded skin

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24h

Score:

0

Max. score:

4

Reversibility:

other: no effects seen

Remarks on result:

other: Abraded skin

Irritant / corrosive response data:

Minimal reactions were seen in the rabbits. Two rabbits exhibited erythema at abraded application sites at 24 and 72 hours after exposure, no other reactions were seen. One rabbit exhibited erythema at the intact skin application site at 24 hours, but this had returned to normal within 72 hours. All rabbits were given scores of 0 for oedema at all time points.

Other effects:

None reported

Dermal irritation scores for individual rabbits exposed to terephthalic acid

Rabbit No.	Abraded Skin:				Intact Skin
	24 hours		72 hours		24 hours		72 hours
	E	O	E	O	E	O	E	O
1	0	0	0	0	0	0	0	0
2	1	0	1	0	1	0	0	0
3	1	0	1	0	0	0	0	0
4	0	0	0	0	0	0	0	0
5	0	0	0	0	0	0	0	0
6	0	0	0	0	0	0	0	0
Mean	0.33	0.00	0.33	0.00	0.17	0.00	0.00	0.00

E: Erythema

O: Oedema

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Terephthalic acid was shown to be a minimal skin irritant under the conditions of this study. The results of the study do not trigger classification of the substance as a skin irritant according to EU criteria.

Executive summary:

Undiluted terephthalic acid (500 mg) was applied to the abraded or intact skin of albino rats, under an occlusive dressing for 24 hours. Minimal reactions were seen in the rabbits. Two rabbits exhibited erythema at abraded application sites at 24 and 72 hours after exposure, no other reactions were seen. One rabbit exhibited erythema at the intact skin application site at 24 hours, but this had returned to normal within 72 hours. All rabbits were given scores of 0 for oedema at all time points. Although not reported in strict compliance with current guidelines, it is clear that the substance is not classified as a skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No information: study reported in 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Older study conducted according to US Department of Transportation guidelines.

Qualifier:

according to guideline

Guideline:

other: DoT corrosion screen

Principles of method if other than guideline:

Corrosivity study

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

Six albino rabbits weighing between 2.5-3.3 kg were used.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g of test material was applied.

Duration of treatment / exposure:

The test substance was applied for 4 hours.

Observation period:

The skin was evaluated at 0, 24 and 48 hours after removal of the test substance and gauze pads.

Number of animals:

6 animals used.

Details on study design:

Six albino rabbits weighing between 2.5-3.3 kg were clipped free of hair on the back and placed in stocks. Doses of 0.5 g of the testmaterial was applied under 1.5" x 1.5", 12-ply cotton gauze pads and the trunk of each rabbit was then loosely wrapped with rubber sheeting. After 4 hours, the rabbits were removed from the stocks, the wrapping and gauze pads were removed and skin reactions were evaluated. The test sites were then washed. Readings were again made at 24 and 48 hours after the initial application.

Irritation parameter:

overall irritation score

Basis:

other: general corrosivity/irritation

Remarks on result:

other: No indications of corrosivity and irritation

Irritant / corrosive response data:

Terephthalic acid is not considered to be corrosive at a dose level of 0.5 g. None of the six rabbits experienced corrosive effects.

Other effects:

There was no effect. Terephthalic acid is not considered to be corrosive.

No further information.

Interpretation of results:

not classified

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Terephthalic acid is not considered to be corrosive.

Executive summary:

In a corrosivity screen, 0.5 g terephthalic acid was applied for 4 hours under occlusive conditions to the shorn dorsal skin of six albino rabbits. No signs of corrosivity were observed at 24 or 48 hours following application. Terephthalic acid is therefore not considered to be a skin corrosive on the basis of this study.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 March to 29 June 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Proprietary non-GLP study, conducted according to OECD guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Remarks:

no certificate or statement of compliance included in report

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

The animals were New Zealand White rabbits of either sex, weighing approximately 2.0-3.5 kg on arrival. Rabbits were supplied by Johnson Rabbit Ranch, IN. The rabbits were acclimatised for at least 1 week prior to study initiation, during which time they were examined to ensure their health and suitability as test subjects,Each rabbit was housed individually in a suspended stainless steel cage. Poly pads were placed in the pans below the mesh.Approximately 150 g of Purina Lab Rabbit Chow HF #5326 (Ralston Purina Co., St. Louis, MO) was provided daily for each rabbit. Reverse osmosis purified water was available ad libitum.Individuals were identified by metal ear tags and corresponding cage cards. Fluorescent lighting was provided on a 12 hour light/dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g undiluted test material was applied (doses were weighed onto aluminium foil).

Duration of treatment / exposure:

4 hours

Observation period:

72 hours after dressing removal

Number of animals:

Three

Details on study design:

Prior to study initiation, the backs of all candidate test animals were shaved and checked for abnormalities. Animals found at this stage to have significant skin abnormalities encompassing the entire shaved back were not included in the study.Approximately 24 hours prior to testing, fur from the trunk of the animals was clipped so that no less than 10% (~240 cm²) of the dorsal body surface was available for application.The treated site was covered by a 2.5x2.5 cm adhesive dressing (Coverlet, Beiersdorf). The entire midsection of each rabbit was then wrapped in a lint free cloth towel secured by Elastoplast. Each rabbit had a treated and an untreated test site, to provide a control for comparison.All wrapping materials were removed 4 hours after application. Following unwrapping, the test sites were rinsed with approximately 2 ml of 0.9% saline and towel dried. All rabbits were weighed immediately prior to application of the test material. All animals were observed for morbidity and mortality at least once daily following treatment. All test sites were examined for signs of dermal irritation (oedema, erythema and/or eschar formation) and corrosivity (ulceration and/or necrosis) 30-60 minutes, 24, 48 and 72 hours after removal of the wrappings. The skin reactions were graded according to the Draize method (Draize, 1959).

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0.2

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

No signs of dermal corrosivity were seen in any rabbit during the study. The irritation score ranged from 0.7/8.0 at 30-60 minutes, to 0.0/8.0 at 72 hours following unwrapping.

Other effects:

No other effects reported.

The irritation score ranged from 0.7/8.0 at 30-60 minutes, to 0.0/8.0 at 72 hours following unwrapping.

The Primary Dermal Irritation Score for terephthalic acid was 0.2.

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The Primary Dermal Irritation Score for Terephthalic Acid was 0.2. No signs of dermal corrosivity were seen in any rabbit during the study.

Executive summary:

Terephthalic acid was applied for 4 hours to the shaved backs of three rabbits at a dose of 0.5 g. Following unwrapping, the test sites were rinsed with saline. All test sites were examined for signs of irritation and corrosivity according to the Draize method at 30 -60 minutes, 24, 48 and 72 hours following removal of the wrappings. No signs of dermal corrosivity were seen in any rabbit during the study. The irritation score ranged from 0.7/8.0 at 30-60 minutes, to 0.0/8.0 at 72 hours following unwrapping. The Primary Dermal Irritation Score for Terephthalic Acid was 0.2. It can be concluded that terephthalic acid is not irritating 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:

No information: study reported in 1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

Eye irritation test in rabbits

GLP compliance:

not specified

Remarks:

: older study, pre-dates GLP

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Albino rabbits

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

100 mg undiluted test substance was applied

Duration of treatment / exposure:

The test substance was applied to the eyes of the rabbits, the eyes were not washed.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

An eye irritation test was conducted on 6 albino rabbits. 100 mg undiluted test substance was applied to the eyes of the rabbits. The test substance was not washed from the eyes. Observations were made at 1, 24, 48 and 72 hours, and 7 days post application.

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

other: No data reported on individual animals

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: effect seen in 1/6 animals

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

2

Reversibility:

other: no effects seen

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-72h

Score:

0.17

Max. score:

3

Reversibility:

fully reversible within: 48h

Remarks on result:

other: effects seen in 6/6 animals

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: effects seen in 6/6 animals

Irritant / corrosive response data:

All irritant effects had disappeared by the 48 hour observation

Other effects:

Conjunctival discharge was additionally noted in 1 rabbit at 24 hours only

Individual rabbit data showing eye irritation scores. The scores given at the 48 and 72 hour and 7 day time points were the same, hence these scores have been given in one column.

Tissue	Rabbit No.	1 hour	24 hours	48 hours, 72 hours, 7 days
Cornea	1	0	0	0
Iris		5	0	0
Conjunctiva		4	0	0
Total		9	0	0
Cornea	2	0	0	0
Iris		5	0	0
Conjunctiva		4	0	0
Total		9	0	0
Cornea	3	0	10	0
Iris		5	5	0
Conjunctiva		4	6	0
Total		9	21	0
Cornea	4	0	0	0
Iris		5	0	0
Conjunctiva		4	0	0
Total		9	0	0
Cornea	5	0	0	0
Iris		5	0	0
Conjunctiva		4	2	0
Total		9	2	0
Cornea	6	0	0	0
Iris		5	0	0
Conjunctiva		4	4	0
Total		9	4	0
Averages
Cornea		0.0	1.7	0
Iris		5.0	0.8	0
Conjunctiva		4.0	2.0	0
Total		9.0	4.5	0

Mean eye irritation scores

Observation		Timepoint
		1h	24h	48h	72h	Mean (24-72h)	7d
Cornea	Opacity	0.00	0.17	0.00	0.00	0.06	0.00
Iris	Lesion	0.00	0.00	0.00	0.00	0.00	0.00
Conjunctivae	Erythema	1.00	0.50	0.00	0.00	0.17	0.00
	Chemosis	1.00	0.33	0.00	0.00	0.11	0.00

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

The substance is a mild eye irritant and does not require labelling as an eye irritant under CLP.

Executive summary:

100 mg undiluted terephthalic acid was instilled into one eye of six albino rabbits and ocular reactions assessd for up to 7 days.

Effects were limited to Grade 1 conjunctival erythema and chemosis in all rabbit, with Grade 1 corneal opacity also apparent in one rabbit at 24 hours only. Conjunctival discharge was addtionally noted in 1 rabit at 24 hours only. The substance is a mild eye irritant and does not require labelling as an eye irritant under CLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation and corrosion potential of terephthalic acid has been investigated in three studies. The results of a guideline-comparable study (with 24 -hour application) show minimal irritant effects on intact skin (Baker, 1975). No evidence of corrosivity was seen in a screening study (DuPont, 1981). The results of an irritation study reported in summary form only (Hatoum & Goun, 1990) are also consistent in indicating a very low potential for dermal irritation.

Eye irritation

A single eye irritation study is available (Baker, 1975), in which 100 mg undiluted terephthalic was applied to the eyes of albino rabbits. One rabbit showed a stronger reaction than the others, but in all cases eyes had returned to normal within 48 hours. Effects were limited to Grade 1 conjunctival erythema and chemosis in all rabbits, with Grade 1 corneal opacity also apparent in one rabbit at 24 hours only. Conjunctival discharge was additionally noted in one rabbit at 24 hours only. Mild irritation was seen in a guideline-comparable study.

Justification for selection of skin irritation / corrosion endpoint:
Guideline compliant study

Justification for selection of eye irritation endpoint:
Only study available for this endpoint

Justification for classification or non-classification

The available studies indicate that terepththalic acid is not classified as a skin or eye irritant, or as corrosive, according to CLP.