Registration Dossier

Administrative data

Description of key information

Oral: Multiple studies are available with a LD50 value of >2000 mg/kg in a weight of evidence approach.

Dermal: An acute dermal toxicity study with rabbit (Goldenthal, 1974) which run on analog substance Benzoic acid (65-85-0) is available which is key study. The LD50 was >2000 mg/kg bodyweight.

Inhalation: An acute inhalation toxicity study with rat (Goldenthal, 1974) which run on analog substance Benzoic acid (65-85-0) is available which is key study. The LC50 was >12200 mg/m3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated 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:
other: Limited study summary, no guideline and no GLP.
Justification for type of information:
Please see Read Across Justification document in Section 13.2 of IUCLID
Reason / purpose:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study predates approved guidelines.
Five male and 5 female rats of the Spartan strain was used in this test. The group of 10 rats was placed in a sealed 59.1 liter glass chamber and exposed for 4 hours to a dynamic atmosphere containing the dust of 12200 mg/m3 test substance.
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
other: Spartan
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: from 226 to 244 grams
- Fasting period before study: not indicated
- Housing: Animals were housed by sex in groups of 5 in metal cages above the dropping.
- Diet (e.g. ad libitum): Purina Laboratory Chow
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Wright Dust Feeder
- Exposure chamber volume: 59.1 liter
- Method of holding animals in test chamber: closed chamber with seperated 4 units of 2 or 3 rats each
- Source and rate of air: Dried and filtered air was passed through the mechanism and directly into the exposure chamber.
- Method of conditioning air: Airflow was regulated by means of a flowmeter.
- System of generating particulates/aerosols: Wright Dust Feeder
- Method of particle size determination: not performed
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
approximately 12200 mg/m3 (The physical properties of the test material preclude the administration of the test compound at higher atmospheric concentrations.)
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 4 hr, 24 hr and 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
none stated
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 12 200 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no deaths following a single inhalation dose of the test substance at 12200 mg/m3 air.
Clinical signs:
other: Increased motor activity and slight erythema were observed during the 4 hour exposure period. After 4 hours exposure, 1 rat exhibited salivation. After 24 hours and after 14 days all animals appeared normal.
Body weight:
Normal body weight gain was observed.
Gross pathology:
No information provided.
Other findings:
No information provided.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 was considered to be >12,200 mg/m3 air. The test substance would not be considered a highly toxic material by the inhalation route of administration.
Executive summary:

Five male and 5 female rats of the Spartan strain was used in this test. The group of 10 rats was placed in a sealed 59.1 liter glass chamber and exposed for 4 hours to a dynamic atmosphere containing the dust of 12200 mg/m3 test substance.

The LC50 was considered to be >12,200 mg/m3 air. The test substance would not be considered a highly toxic material by the inhalation route of administration.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
12 200 mg/m³
Quality of whole database:
2 (reliable with restrictions)

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated 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:
other: Limited study summary, no GLP, deviations compared to OECD 402
Justification for type of information:
See Read Across Justification document in Section 13.2 of IUCLID
Reason / purpose:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
4 rabbits were dermally exposed (semi-occlusive) for 24 hours to the test substance (2000 mg/kg). Observation for mortality during 24 hours.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2311 - 2812 grams
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
No additional data

ENVIRONMENTAL CONDITIONS
No information provided

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the back
- % coverage:
- Type of wrap if used: gauze bandages and Saran Wrap


REMOVAL OF TEST SUBSTANCE
- Washing (if done): tepid water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): undiluted
- For solids, paste formed: no


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
2 male and 2 female per dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated
- Necropsy of survivors performed:
- Other examinations performed: body weight,organ weights
Statistics:
None stated
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
No information provided
Body weight:
Normal body weight gains was observed.
Gross pathology:
No information provided
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was considered to be >2,000 mg/kg bw. The test substance would not be considered a toxic substance by the dermal route of administration.
Executive summary:

4 rabbits were dermally exposed (semi-occlusive) for 24 hours to the test substance (2000 mg/kg). Observation for mortality during 24 hours.

The LD50 was considered to be >2,000 mg/kg bw. The test substance would not be considered a toxic substance by the dermal route of administration.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
2 (reliable with restrictions)

Additional information

Oral: 6 studies are referenced in the dossier. These are as follows:

1) Rat LD50 = 2100 mg/kg (Deuel, 1953)

2) Rat LD50 = 3450 mg/kg (Weil, 1953)

3) Rat LD50 = 4070 mg.kg (Smyth, 1948)

4) Rat LD50 = 3140 mg/kg (Loeser, 1977)

5) Rat LD50 = 1714 mg/kg (Hager, 1942)

6) Rat LD50 > 5000 mg/kg (Fabrizio, 1974)

All of the studies showed defencies in the reporting of the test protocol and methods used. Two studies were rated with Klimisch 2 (Weil, 1953 and Fabrizio, 1974), both showing LD50 values > 2000 mg/kg bw. Only the study by Hager (1942) gave a lower LD50. The result of this study is, however, assessed based on data that are only available in secondary references. Therefore it is concluded that the oral LD50 is > 2000 mg/kg bw.

Dermal: No studies on acute dermal toxicity with the test substance are available, but an acute dermal toxicity study with rabbit (Goldenthal, 1974) run on the stuctural analog substance Benzoic acid (65-85-0) is available.

This study showed some deviations from the guideline, but was considered sufficient to determine that the LD50 was >2000 mg/kg bodyweight. Therefore the LD50 for the test substance is concluded to be >2000 mg/kg bw.

Inhalation:

No studies on acute inhalation toxicity with the test substance are available, but an acute inhalation toxicity study with rats (Goldenthal, 1974) exposed to the structural analog benzoic acid dust is available. This study showed slight deviations from the guideline, but was considered sufficient to determine that the LC50 was >12200 mg/m3 (maximum concentration technically possible). Therefore the LC50 for the test substance is set at > 12200 mg/m3

Justification for selection of acute toxicity – inhalation endpoint

Only one read-across study from benzoic acid is available.

Justification for selection of acute toxicity – dermal endpoint

Only one read-across study from benzoic acid is available.

Justification for classification or non-classification

Oral LD50 = >2,000 mg/kg (weight of evidence)

Dermal LD50 = >2,000 mg/kg (actual value read across >2,000 mg/kg)

Inhalation LD50 = >5,000 mg/m3 (actual value read across >12,200 mg/m³)

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.1.1 the substance is not classified for the acute toxicity endpoint.