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Administrative data

Description of key information

Oral ALD, rat = 5000 mg/kg, Reliability = 2
Dermal LD50, rabbit > 2000 mg/kg [CAS# 100-21-0], Reliability = 2
Inhalation, 4-hr LC50, rat = 700 mg/m3, Reliability = 2

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
One animal per group.
Principles of method if other than guideline:
The test substance, as a suspension in corn oil, was administered by gavage to young adult male rats in a single dose (1 rat/dose level). Dose levels were 670, 1500, 2500, 3400, 5000, 7500 mg/kg. Survivors were sacrificed 14 days later. Animals were observed for toxic signs, body weight changes, mortality and moribunditity.
GLP compliance:
not specified
Test type:
standard acute method
Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
10% suspension for concentrations of 670-2250 mg/kg.
20% suspension for concentrations of 3400-7500 mg/kg.
Doses:
670, 1500, 2250, 3400, 5000, 7500 mg/kg. The highest dose was administered in divided dose.
No. of animals per sex per dose:
1 rat/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration was 14 days.
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: Not reported
- Other examinations performed: Clinical signs and body weight.
Sex:
male
Dose descriptor:
other: approximate lethal dose (ALD)
Effect level:
5 000 mg/kg bw
Mortality:
At 7500 mg/kg death at day one.
At 5000 mg/kg death at day six.
Clinical signs:
Lethal doses: Discomfort and inactivity after dosing. Irregular respiration on day of dosing. Heavy breathing, weakness, blood in urine, absence of faeces for 2 days.
Non-lethal doses: Discomfort and inactivity after dosing. Irregular respiration on day of dosing, blood-stained mouth, and mild diarrhoea for 1 day.
Body weight:
Lethal doses: Continuous weight loss at 5000 mg/kg.
Non-lethal doses: Weight loss for 2 days at 3400 mg/kg. Initial weight loss at 1500 and 2250 mg/kg.
Gross pathology:
Not reported.
Interpretation of results:
GHS criteria not met
Conclusions:
ALD = 5000 mg/kg
Executive summary:

The test substance, as a suspension in corn oil, was administered by gavage to young adult male rats in a single dose (1 rat/dose level). Dose levels were 670, 1500, 2500, 3400, 5000, 7500 mg/kg. Survivors were sacrificed 14 days later. Animals were observed for toxic signs, body weight changes, mortality and moribunditity. The ALD was 5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study was conducted under non-standard guideline (Class B Poison Test).
Principles of method if other than guideline:
Six young adult male rats per dose level were exposed whole body to 0.12, 0.38, 0.60, 0.66, 2.31 mg/L of the test substance for four hours. Rats were sacrificed and necropsied at one, two, and six days after exposure to 0.12 mg/L and 14 days after exposure to 0.6 mg/L.
GLP compliance:
not specified
Test type:
other: Class B Poison Test
Species:
rat
Strain:
other: ChR-CD
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 250-280 grams
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: air; (nitrogen was used to pass chemical into exposure chamber where it was then mixed with oxygen and diluting air to give an 20% O2 (v/v) concentration)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Bell jar
- Exposure chamber volume: 16 litre
- Method of holding animals in test chamber: Whole body
- System of generating particulates/aerosols: The test substance was put in a three-neck glass flack in a heated (100°C) mineral oil bath. Aerosols of the compound were prepared from this molten test substance by a stainless steel nebulizer submerged into the melt. Nitrogen was passed through the nebulizer to carry the vapours into a 16-liter bell-jar containing six young adult male rats. Oxygen and diluting air were added to the stream prior to entering the exposure changer to give 20% oxygen (v/v) in the chamber atmosphere and to adjust the concentration.

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration determined at least three times during each 4 hour exposure by drawing a known volume of chamber atmosphere through two impingers in series. n-Heptane was the scrubbing solvent. The solution was analyzed by ultraviolet light absorption at 254 mµ.
- Samples taken from breathing zone: Yes

VEHICLE
- Composition of vehicle (if applicable): Nitrogen was used to pass chemical into exposure chamber where it was then mixed with oxygen and diluting air to give an 20% O2 (v/v) concentration.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Concentration determined at least 3 times during each 4 hour exposure by drawing a known volume of chamber atmosphere through 2 impingers in series. n-Heptane was the scrubbing solvent. The solution was analyzed by ultraviolet light absorption at 254mµ.
Duration of exposure:
4 h
Concentrations:
0.12, 0.38, 0.60, 0.66, 2.31 mg/L
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: Up to 14 days
- Frequency of observations and weighing: Weight measured daily.
- Necropsy of survivors performed: Yes. Rats were sacrificed at one, two and six days after exposure to 0.12 mg/L and 14 days after exposure to 0.6 mg/L. Tissues examined included: lungs, liver, kidney, brain, lymph nodes, spleen, testes, gastrointestinal tract, thyroid, adrenal, skin, bone marrow, pancreas, epidedymis, thymus, and eye.
- Other examinations performed: Clinical signs during exposure
Statistics:
Statistical analysis by method of Litchfield, J. T., Jr. and F. Wilcoxon, J. Pharmacol. and Expt'l. Therap., 96:99 (1949).
Sex:
male
Dose descriptor:
LC50
Effect level:
0.7 mg/L air
95% CL:
0.46 - 1.06
Exp. duration:
4 h
Mortality:
0/6 at 0.12 mg/L; 1/6 at 0.38 mgL; 2/6 at 0.60 mg/L; 3/6 at 0.66 mg/L; and 6/6 at 2.31 mg/L.
Clinical signs:
other: 0.12 mg/L- During exposure: Slight difficulty breathing, otherwise normal 0.38 mg/L- During exposure: Heavy breathing, occasional face pawing, gasping. One death at 2.5 hours 0.60 mg/L- During exposure: Lacrimation, face pawing, heavy breathing and gaspin
Body weight:
0.12 mg/L- Down to 82% of their initial body weight on the 1st day.
0.38 mg/L- Down to 76% of initial body weight on the 2nd day post-exposure, normal recovery thereafter.
0.60 mg/L- Down to 83% of initial body weight on the 1st day of recovery, normal recovery thereafter.
0.66 mg/L- Down to 82% of initial body weight 1st day post-exposure. All but one started to recover 2nd day post-exposure. The one was down to 75% of initial body weight on the 5th day of recovery and gained normally thereafter.
Gross pathology:
Rats were sacrificed at one, two, and six days after exposure to 0.12 mg/L and 14 days after exposure to 0.6 mg/L. The rat which died during exposure to 0.38 mg/L and one of those which died during exposure to 2.31 mg/L were also necropsied for gross and histopathologic examination. Gross examination at necropsy revealed severe pulmonary oedema and congestion.
Slight pulmonary congestion and oedema were still noted in rats sacrificed one day post-exposure. They also showed acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells and depletion of hepatic cell glycogen.
The rats sacrificed two days post-exposure showed no evidence of pulmonary oedema, but glycogen depletion of the hepatic cells was still evident.
Rats sacrificed at six and 14 days post-exposure exhibited regeneration of the tracheobronchial epithelium and had normal amounts of glycogen in the hepatic cells.
Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.

Decreased body weight days 1-5 days post exposure and normal thereafter. Slight pulmonary congestion and oedema; acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells; and depletion of hepatic cell glycogen were observed one day post exposure. At two days post exposure, no evidence of pulmonary oedema was observed, but glycogen depletion of the hepatic cells was still evident. At 6 and 14 days post exposure regeneration of the tracheobronchial epithelium and normal amount of glycogen in the hepatic cells were observed. Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
LC50 = 0.7 mg/L
Executive summary:

Male rats were exposed to the test substance for 4 hours by inhalation at concentrations of 0.12, 0.38, 0.60, 0.66 and 2.31 mg/L. The LC50 was 0.7 mg/L. Decreased body weight was observed on days 1-5 days post exposure and was normal thereafter. Slight pulmonary congestion and edema; acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells; and depletion of hepatic cell glycogen were observed one day post exposure. At two days post exposure no evidence of pulmonary edema was observed but glycogen depletion of the hepatic cells was still evident. At 6 and 14 days post exposure regeneration of the tracheobronchial epithelium and normal amount of glycogen in the hepatic cells were observed. Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
700 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
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). Limit test performed under GLP requirements.
Principles of method if other than guideline:
The test substance (a neat powder) was administered to the backs of 5 male and 5 female rabbits at a dose level of 2000 mg/kg bw and covered with an occlusive wrap. Prior to application, the backs were shaved and moistened with water. The test substance was left in contact with the skin for 24 hours and then removed. Body weights were assessed at dosing, and on Days 7 and 14. Animals were observed daily for 14 days at which time they were sacrificed and necropsied.
GLP compliance:
yes
Limit test:
yes
Species:
rabbit
Strain:
other: New Zealand
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Johnson Rabbit Ranch (Wilkinson, IN)
- Age at study initiation: approximately 3 months of age
- Weight at study initiation: 2.59 kg (males) and 2.45 kg (females)
- Housing: Individually in stainless steel cages measuring 61.0 x 45.5 x 41.0 cm. Poly pads were placed in the pan below the stainless steel mesh floor of each animal cage to absorb liquids.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.7°C
- Humidity (%): 32%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Prior to application, the backs were shaved and moistened with water. Body weights were assessed at dosing, and on Days 7 and 14. Animals were observed daily for 14 days at which time they were sacrificed and necropsied.

TEST SITE
- Area of exposure: The shaved application site (approximately 240 cm2 on the back of each rabbit) was pre-moistened with water immediately prior to test article administration.
- % coverage: The test substance was covered with a 12.8 x 23.0 cm surgical dressing
- Type of wrap if used: Plastic film, secured by lint-free cloth and elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was wiped gently with gauze and 0.9% saline to remove residual test article.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g
- For solids, paste formed: The shaved application site was pre-moistened with water immediately prior to test substance administration.
Duration of exposure:
24 hours
Doses:
2 grams
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All test rabbits were observed approximately 3/4, 3-1/4, 4-1/4 and 5-1/4 hours after dosing and at least once per day for 14 days after removal of the wrappings.
- Necropsy of survivors performed: Yes, a limited gross necropsy was performed on all test animals.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Body weights were assessed at dosing, and on Days 7 and 14.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
The only clinical signs noted consisted of an erythema at the application site immediately after unwrapping in 2/5 males and 4/5 females.
Body weight:
Mean body weights increased during the study.
Gross pathology:
No gross pathological lesions attributable to treatment were evident in any of the rabbits at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
Rabbit dermal LD50 > 2000 mg/kg bw
Executive summary:

The test substance (a neat powder) was administered to the backs of 5 male and 5 female rabbits at a dose level of 2000 mg/kg bw and covered with an occlusive wrap. Prior to application, the backs were shaved and moistened with water. The test substance was left in contact with the skin for 24 hours and then removed. Body weights were assessed at dosing, and on Days 7 and 14. Animals were observed daily for 14 days at which time they were sacrificed and necropsied. No deaths occurred during the study. The only clinical signs noted consisted of an erythema at the application site immediately after unwrapping in 2/5 males and 4/5 females. Mean body weights increased during the study. No gross pathological lesions attributable to treatment were evident in any of the rabbits at necropsy. The dermal LD50 was greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Oral

The test substance, as a suspension in corn oil, was administered by gavage to young adult male rats in a single dose and survivors were sacrificed 14 days later. Animals were observed for toxic signs, body weight changes, mortality and moribunditity. The ALD was 5000 mg/kg.

Dermal

No data were available for the test substance. The test substance rapidly hydrolyses to terephthalic acid (TPA). Therefore, a dermal study with TPA is being used to fulfill this data requirement. Additional documentation, provided within the IUCLID Assessment Report section, supports the read-across approach.

A single dose of 2000 mg/kg test material was applied on the back of New Zealand rabbits and covered with an occlusive wrap. No deaths were noted in either sex. The only clinical signs noted consisted of an erythema at the application site immediately after unwrapping in 2/5 males and 4/5 females. All animals appeared normal by Day 4.

Inhalation

Male rats were exposed to the test substance for 4 hours by inhalation at concentrations of 0.12, 0.38, 0.60, 0.66 and 2.31 mg/L. Decreased body weight was observed on days 1-5 days post exposure and was normal thereafter. Slight pulmonary congestion and edema; acute necrotic tracheobronchitis, hyperplasia of granular alveolar cells; and depletion of hepatic cell glycogen were observed one day post exposure. At two days post exposure no evidence of pulmonary edema was observed but glycogen depletion of the hepatic cells was still evident. At 6 and 14 days post exposure regeneration of the tracheobronchial epithelium and normal amount of glycogen in the hepatic cells were observed. Depletion of glycogen in the hepatic cells was considered a transient change due to stress and anorexia following exposure and reflected the nutritional condition of the test rats. The LC50 was 0.7 mg/L (700 mg/m3).

Justification for classification or non-classification

Based on the oral rat ALD of 5000 mg/kg with the test substance and dermal LD50 in rabbits of >2000 mg/kg with the hydrolysis substance, the test substance is not classified for acute oral or dermal toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on the rat 4-hour inhalation LC50 value of 700 mg/m3 air, the substance is classified as and Cat 3 (H331: Toxic if inhaled) for acute inhalation toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Additionally, data suggest the potential for respiratory irritation; therefore, the substance is classified for STOT SE as Cat 3 (H335: May cause respiratory irritation) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.