Reaction products of diazotised 2-amino-5-nitrobenzenesulfonic acid coupled with resorcinol, subsequently coupled with diazotized 2-amino-4-nitro-6-sulfo-phenol, chelated with iron, sodium salt

Endpoint summary

Description of key information

Oral route: LD₅₀ > 2000 mg/kg.

Inhalation: LC₅₀ > 1.88 mg/L.

Intraperitoneal route: LD₅₀ > 2000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

November 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Source study has reliablity 2. Details on the read across are attached in section 13.

Qualifier:

no guideline available

Principles of method if other than guideline:

Acute toxicity in rats assessed in limit test at dose of 5000 mg/kg by oral route. Observations were continued for up to 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 % in water

Details on oral exposure:

Concentration in vehicle: 50 % m/v
Maximum volume applied: 10 ml/kg

Doses:

5000 mg/kg

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

ca. 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Brown urine

Interpretation of results:

GHS criteria not met

Conclusions:

LD0 = 5000 mg/kg
LD50 > 5000 mg/kg

Executive summary:

Method:

Test substance was administered to 5/rat/sex by gavage at dose of 5000 mg/kg. Test animals were observed for 14 days after dosing.

 

Results:

No mortality was recorded, thus LD₀ = 5000 mg/kg and LD₅₀ > 5000 mg/kg.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

April 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Source study has reliablity 2. Details on the read across are attached in section 13.

Principles of method if other than guideline:

Acute toxicity in rats assessed in a limit test at dose of 2000 mg/kg by oral route. Observations were continued for up to 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd.
- Weight at study initiation: 195 - 300 g.
- Fasting period before study: 18 - 20 h before treatment.
- Housing: in groups of 5 by sex.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: 3 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 50 ± 10%
- Photoperiod: natural lighting conditions.

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2000 mg/kg bw based on the individual fasted body weight of the animals at the time of treatment.

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: observations for overt toxicity and mortality at 15 min, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days; body weights of survivors at 7 and 14 days after treatment.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: No signs of overt toxicity.

Interpretation of results:

GHS criteria not met

Conclusions:

LD0 = 2000 mg/kg
LD50 > 2000 mg/kg

Executive summary:

Method:

Test substance was administered to 5/rat/sex by gavage at dose of 2000 mg/kg. Test animals were observed for 14 days after dosing.

 

Results:

No mortality was recorded, thus LD₀ = 2000 mg/kg and LD₅₀ > 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

June 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Source study has reliablity 2. Details on the read across are attached in section 13.

Principles of method if other than guideline:

Test group (10/rat/sex): a single maximum concentration of test substance as a dust by inhalation (nose only) over a period of 4 hours.
Control group (5/rat/sex): atmosphere of filtered air under similar conditions as test group.

GLP compliance:

no

Test type:

fixed concentration procedure

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories.
- Age at study initiation: aged 7 - 8 weeks.
- Weight at study initiation: 180 - 200 g.
- Housing: group of 5 by sex.
- Diet: ad libitum except during exposure period.
- Water: ad libitum except during exposure period.
- Acclimation period: 15 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C.
- Humidity: 50 ± 10%.
- Air changes: 8 -10 air changes per hour.
- Photoperiod: controlled lighting conditions.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: dried air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Timbrell dust generator.
- Exposure chamber volume: 7 litres capacity.
- Flow rate: 10 l/min.

TEST ATMOSPHERE: mean particle size of the respirable fraction of the atmosphere generated was 1.83 µm.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric analysis

Duration of exposure:

4 h

Concentrations:

1.88 mg/l (gravimetric analysis)
43.8 mg/l (nominal concentration)

No. of animals per sex per dose:

test group: 10/sex
control group: 5/sex

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations: daily.
- Frequency of weighing: 1 day before exposure and on day 1, 2, 4,8, 11 and 15 after exposure.
- Necropsy of survivors performed: yes, if no deaths accurred during exposure, 1 male and 1 female from each group were killed and subjected to gross necropsy.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.88 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC0

Effect level:

ca. 1.88 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths occurred during exposure or during the observation period as a result of exposure to test substance. One female treated rat suffocated as a result of turning around in the restraining tube. A planned sacrifice was made of 1 male treated rat, 1 male control and 1 female control rat after exposure to assess the degree of primary lung irritation.

Clinical signs:

other: Male and female animals reacted in the same way to the dust. All animals developed chromodacryorrhoea during exposure for a few hours post exposure. The respiration was shallow after exposure but returned to normal an the day after exposure.

Body weight:

The mean body weights of the male and female control rats rose throughout the experiment, slowly until day 2 but thereafter more rapidly. The mean body weight of the treated rats was depressed following exposure but rose steadily during the observation period.

Gross pathology:

All control rats and the majority of the treated rats sacrificed after the observation period showed a moderate degree of pulmonary congestion, and pulmonary oedema was noted in some control rats. The female rat which died during exposure and the male rat which was sacrificed immediately after exposure showed only slight pulmonary congestion. No lesions were seen in the other major organs examined.

Atmosphere control:

The heterogeneous nature of the article did not facilitate the generation of an atmosphere with a uniformly small particle size. lt is believed that the apparent low percentage transfer of dust from the generator to the sample orifice on the side of the exposure chamber was due to:

(i) Deposition of the larger particles on the generator transfer pipe

(ii) Production of a heterogeneous atmosphere in the exposure chamber. Observation of the floor of the exposure chamber after exposure showed a higher deposit of dust in the centre. Consequently the atmosphere probably had a higher concentration of aerodynamically less stable, larger particles in the centre. Therefore, samples drawn from the side of the chamber did not contain a representative fraction of all particles produced, but only those which were available to the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 > 1.88 mg/l after a 4-hour exposure.

Executive summary:

Method:

A single maximum concentration of test substance was given to 20 rats (10 male, 10 female) as a dust by inhalation (nose only) over a period of 4 hours. A further 10 rats (5 male, 5 female) were exposed under similar conditions to an atmosphere of filtered air. The concentration of test substance measured by gravimetric analysis was 1.88 mg/L.

Aerodynamic mass median diameter of dust particles was 1.83 µm.

 

Results:

No substance-related deaths occurred during exposure nor in the following observation period.

All treated animals showed the following signs for 1 -2 days post exposure: chromodacryorrhoea, shallow respiration, discoloured faeces, stained and ruffled fur.

The animals remained alert and their pelts remained stained throughout the observation period. The control animals had chromodacryorrhoea and nasal secretion on the exposure day only. The pelts remained ruffled throughout the observation period.

Mean body weights of male and female control rats rose throughout the experiment, slowly until day 2 but thereafter more rapidly.

The mean body weight of the treated rats was depressed following exposure but rose steadily during the observation period.

Pulmonary congestion was noted in all the control animais. In the treatment group there was a slight to moderate degree of pulmonary congestion in the rats, which were sacrificed at the end of the 14-day observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), substances can be allocated to one of four toxicity categories based on acute toxicity by oral, dermal or inhalation route according to numeric criteria. Acute toxicity values are expressed as LD50 (oral, dermal) or LC50 (inhalation) values as well as acute toxicity estimates (ATE).

 

Oral LD50 above 2000 mg/kg bw was found, thus target substance was not classified for acute oral toxicity in the CLP Regulation (EC 1272/2008).

During the Acute inhalation toxicity test, no mortality was observed at the highest tested concentration. No classification is warranted according the CLP Regulation (EC 1272/2008).