2-phenyl-1H-benzimidazole-5-sulphonic acid

Endpoint summary

Description of key information

 The substance is neiter classifiable for acute oral toxicity nor for acute dermal toxicity. An inhalative study is not available and not required considering the low vapour pressure of the substance and its use in cosmetic skin formulations.

 

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

Study period:

1971

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 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

study was performed prior to OECD guideline availability but followed in principle the method as described there. The toxicity of the test material after oral administration was studies in Wistar rats. A 16.5% solution of the test item was administered orally (gavage) to 10 animals at a volume of 40 mL/kg body weight (bw) resulting in a dose of 6600 mg/kg. After an observation period of 14 days the animals were killed and investigated for macroscopic signs of pathological changes.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

other: mouse and rat

Strain:

other: mouse--CF-1; rat--Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Experimental animals and housing conditions
Animals employed in this study were male SPF-bred mice of the strain CF1 with a mean weight of about 20 g and male SPF-bred Wistar rats with a mean weight of 220 g.
The mice had been supplied by Winkelmann - Kirchborchen, the rats by Mus Rattus AG, Brunnthal near Munich. Mice and rats were housed in groups of 5 animals each in Makrolon Type I and Type III cages, respectively, at a room temperature of about 22 °C and natural light.They received pellets of dry feed (supplier, Altromin GmbH, Lage/Lippe) and water ad libitum.

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Test article-Na solution was administered in its present form as a 16.5% concentration with an application volume of 40 ml/kg body weight, which is, for technical reasons, the maximum volume to be applied. Administration to mice and rats was performed using a gavage. Prior to application the animals were kept non-fasted.

Doses:

6600 mg were administered as a 16,5% Novantisol-Na solution at a volume of 40 ml/kg body weight.

No. of animals per sex per dose:

10 mice; 10 rats

Control animals:

not specified

Details on study design:

Signs and deaths occurring during a 14-day observation period were recorded in the study records. After the observation period the animals were sacrificed and necropsied.

Statistics:

Calculation of the LD50 on the confidence level of p=0.5 is usually performed with the program-controlled probit analysis according to FINK and HUND.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 6 600 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 6,600 mg test article-Na was tolerated by the animals investigated without signs.

Mortality:

No mortality was observed throughout the observation period (14 days).

Clinical signs:

other: Acute toxicity of test article-Na in mice after oral administration: 6,600 mg test article-Na was tolerated by the mice investigated without signs. As the 6,600 mg were administered as a 16.5 % Test article-Na solution at a volume of 40 ml/kg body weight

Gross pathology:

Necropsy of the mice sacrificed after a 14-day observation period gave no indication of macroscopically noticeable pathological changes.
Neither did necropsies of rats after 14 days of observation give any indication of pathological organ changes.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (oral, rat/mouse): >6600 mg/kg body weight

Executive summary:

This acute toxicity of test article was performed with mice and rats at a single concentration of 6600 mg/kg body weight by oral gavage. As the 6,600 mg were administered as a 16.5 % Test article-Na solution at a volume of 40 ml/kg body weight and administration of a higher dose was not possible for technical reasons, no lethal dose could be established. Necropsy of the animals sacrificed after a 14-day observation period gave no indication of macroscopically noticeable pathological changes.

In conclusion, LD50 of sodium salt of test article is considered to be greater than 6600 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 600 mg/kg bw

Quality of whole database:

Besides the key study performed with sodium salt of test substance also two supportive studies are available, one performed with the sodium salt of test substance (LD50 >16000 mg/kg bw) and one with the substance itself (LD50 >5000 mg/kg bw). Thus, there is a solid basis for considering this substance practically non toxic.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1974

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 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive patch was used

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: EMD SPF
- Weight at study initiation: 148 (121 - 176) g
- Housing: separately in Macrolon Type III cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 26 °C
- Humidity (%): 42 - 47 %

IN-LIFE DATES: From: day 1 To: day 14

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 6 cm
- % coverage: 10
- Type of wrap if used: tin foil fixed and sealed with rubber sleeve

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 mL / 100 g bw
- Concentration (if solution): 30 % in water
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

3000 mg/kg bw

No. of animals per sex per dose:

10 (5m, 5f)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily for 2 weeks
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Statistics:

no statistics

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed. All animals survived the observation period (14 days).

Clinical signs:

other: On the day of treatment the mobility and well-being of the rats were necessarily limited by the rubber sleeve applied. After 24 hours all rats were free from symptoms. No local effects were observed at the treated skin sites.

Gross pathology:

No pathologicol-anatomical changes were observed in any of the rats.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study the dermal LD50 of Phenylbenzimidazole sulfonic acid (Na-salt) in rats is > 3.000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test material was investigated in Wistar-AF rats.

A 30 % aqueous solution of the test item corresponding to a dose of 3000 mg/kg bw was applied on the shaved skin of 5 male and 5 female rats for 24 hours under occlusive conditions (tin foil fixed and sealed with rubber sleeve). After 24 hours the tin foil was removed and residual test item was washed off with water. The rats were observed and weighed daily for 14 days.

Changes at the application site were rated according to Draize (FDA Appraisal, Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics by FDA, Baltimore Md. 1959, page 51).

No mortalities were observed during the observation period of 14 days. No local effects were observed at the treated skin sites. At necropsy no pathological changes were observed in any of the rats.

Based on the results of this study the dermal LD50 of Phenylbenzimidazole sulfonic acid (Na-salt) in rats is > 3.000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 000 mg/kg bw

Quality of whole database:

Two studies are available providing very consistent results, although neutralized with different alkali.

Additional information

Oral

Besides the key study performed with sodium salt of test substance (LD50 >6600 mg/kg bw) also two supportive studies are available, one performed with the sodium salt of test substance (LD50 >16000 mg/kg bw) and one with the substance itself (LD50 >5000 mg/kg bw). Thus, there is a solid basis for considering this substance practically non toxic.

Dermal

Two studies are available for acute dermal toxicity, one applying a 30 % solution of sodium hydroxide neutralized test substance and one using triethanolamine neutralized test substance in aqueous solution to the back skin of rats. In both tests 3000 mg/kg bw were dermally applied and the LD50 (dermal rat) was established at >3000 mg/kg in both. Thus, in a weight of evidence approach the substance is considered not classifiable for acute dermal toxicity.

Inhalative

An inhalative study is not available and not required considering the low vapour pressure, the particle size distribution of the substance and its use in cosmetic skin formulations.

Justification for classification or non-classification

Based on the acute oral toxicity results (LD50 >6600 mg/kg bw) and the acute dermal toxicity results (LD50 >3000 mg/kg bw) the substance does not require classification according to CLP (Regulation EC No 1272/2008).

As the substance is solid and not of hydrocarbon nature, aspiration hazard classification is not appropriate.

According to regulation (EC) 1907/2006 Annex XI (weight of evidence), testing for acute inhalation toxicity is not considered to be required, for the following reasons:

- 2-phenyl-1H-benzimidazole-5-sulphonic acid has a negligible vapour pressure. Thus an acute 4-hour inhalation study would be carried out at the limit dose of 5 mg/L aerosol. Assuming a very conservative value of 100 % bioavailability, a rat would receive a systemic dose of 0.8 L/min/kg x 240 min x 5 mg/L aerosol = 960 mg/kg.

- Since the acute oral LD50 was higher than this value, it is considered unlikely that mortality would be observed in an acute inhalation study.

- With regard to possible local respiratory effects, 2-phenyl-1H-benzimidazole-5-sulphonic acid is not classified for skin or eye irritation and showed no irritation effects on skin or on the mucosal membranes of the eyes. Therefore, 2-phenyl-1H-benzimidazole-5-sulphonic acid is considered unlikely to exert a relevant local irritative effect on respiratory mucosal membranes.

Therefore, performance of an acute inhalation study is considered not necessary for scientific reasons and 2-phenyl-1H-benzimidazole-5-sulphonic acid is considered unlikely to exert effects upon inhalation that would require classification according to CLP (Regulation (EC) No. 1272/2008.