Registration Dossier

Administrative data

Description of key information

Skin: no skin irritation was observed in rabbits at 34.5 mg/cm2; reliability = 2. 

Eye: OECD 405; no eye irritation was observed in rabbits at 100 mg/eye; reliability = 2; [CAS# 100-21-0]

While the material is not classified as a corrosive based on experimental data provided, it is known that an association with water produces the products of hydrolysis (organic acid and HCl) which would be expected to be corrosive to the skin and eye. The submitter acknowledges that in reality, exposure to human skin and eyes would include moisture, leading to a corrosive condition with sufficient exposure time and is classified as Cat 1A for skin corrosion and Cat 1 for eye damage.

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:
4 hours
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to
Guideline:
other: Department of Transportation, Hazardous Material Regulations, Title 49 CFR, Section 173.240(a)(1), December 31, 1973
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Housing: FDA-type stocks.
Type of coverage:
other: applied to skin under gauze pad.
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 grams of the test substance was applied under 1.5 by 1.5 inch (14.5 cm2), 12-ply cotton gauze pads and the trunk of each rabbit was then loosely wrapped with rubber sheeting. The overall dose that was applied equated to 34.5 mg/cm2)
Duration of treatment / exposure:
4 hours
Observation period:
4, 24, and 48 hours
Number of animals:
6
Details on study design:
Animals were placed in an FDA-type stock. The test substance was applied to the clipped skin on the animal's back and covered with cotton gauze loosely wrapped with rubber sheeting. After 4 hrs, the rabbits were removed from the stocks, the wrappings 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:
erythema score
Basis:
other: all animals
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Remarks:
irritation read only at 24 and 48 hours
Irritation parameter:
edema score
Basis:
other: all animals
Time point:
24/48/72 h
Remarks on result:
other: not reported
Irritant / corrosive response data:
0/6 rabbits exhibited skin corrosion.
Other effects:
N/A

0/6 of the rabbits exhibited skin corrosion after 4, 24, and 48 hours.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was deemed not corrosive based on the requirements of the Department of Transportation, Hazardous Material Regulations, Title 49 CFR, Section 173.240(a)(1), December 31, 1973.
Executive summary:

The test substance was applied at a dosage of 34.5 mg/cm2to the shaved skin of six Albino rabbits. The test substance was applied to the clipped skin on the animal's back and covered with cotton gauze loosely wrapped with rubber sheeting. After 4 hrs, the rabbits were removed from the stocks, the wrappings 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. None of the rabbits exhibited skin corrosion after 4, 24, and 48 hours.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
This study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions). The study, if used in support of terephthalic acid, has a reliability of 1 (reliable without restriction).
Justification for type of information:
The test substance rapidly hydrolyses to isophthalic acid (IPA) and IPA is structurally similar to terephthalic acid (TPA). Therefore, the study with TPA is being used to fulfil this data requirement. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.
Reason / purpose:
read-across: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
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
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:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
110
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
1.7
Max. score:
110
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0.8
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
other: not reported
Irritant / corrosive response data:
All irritant effects had disappeared by the 48 hour observation. One rabbit was assigned a score of 10 for corneal irritation at the 24 hour time point, but returned to normal by the 48 hour observation. No other corneal effects were observed. Individual animal data are presented in Table 1.
Other effects:
not reported.

Table 1. 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

 

Interpretation of results:
GHS criteria not met
Conclusions:
The author classified the test substance not irritating to the eyes of rabbits
Executive summary:

Limited information is available regarding this study. 100 mg undiluted test substance 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. The average irritation score 1 hour after application was 9.0 (out of 110), and at 24 hours was 4.5 (out of 110). The author classified the test substance as non-irritating to rabbit eyes.

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

Data on the parent chemical itself has been shown to not be an irritant or corrosive in experimental animal studies. While the material is not classified as corrosive based on experimental data provided, it is known that an association with water produces the products of hydrolysis (organic acid and HCl) which would be expected to be corrosive to the skin and eye. The submitter acknowledges that in reality, exposure to human skin and eyes would include moisture, leading to a corrosive condition with sufficient exposure time. Therefore, the chemical warrants classification as corrosive to the skin and eye, Cat 1A (Causes severe skin burns and eye damage) for skin irritation and Cat 1 (Causes serious eye damage) for eye irritation according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.