Reaction products of 4-amino-3-hydroxy-7-nitronaphthalene-1-sulfonic acid and 2′,4′-dihydroxyacetophenone chelated with iron, sodium salts

Endpoint summary

Description of key information

Acute oral toxicity in rat: LD₅₀ > 2200 mg/kg bw

            

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:

supporting study

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 reliability 1. Details on the read across are available in section 13.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

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: Dr. K. Thomae GmbH, 7950 Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: mean 220 g (males), 191 g (females)
- Fasting period before study: 16 hours before administration, but water was available ad libitum
- Housing: five per cage in stainless steel wire mesh cages, type DK III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least one week


ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod: 12/12 (hrs dark / hrs light)

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg

Doses:

5000 mg/kg bw

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: recording of signs and symptoms several times on the day of administration, then at least once each workday. Check for moribund and dead animals twice each workday and once daily at weekends and on holidays. Body weights were recorded shortly before administration and on day 3, 7 and 13.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Statistics:

LD50 was calculated according to Probit or other suitable methods

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: Black feces on days 1-3

Gross pathology:

No abnormalities detected.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rat, oral) > 5000 mg/kg bw.

Executive summary:

Method:

Acute oral toxicity in rats was assessed following OECD guideline 401. A dose of 5000 mg/kg bw was administered by gavage 5 rats/sex. A 14-days observation period followed dosing.

Results:

No mortality was recorded, thus LD₅₀ > 5000 mg/kg. Black discoloured feces were noted in both males and females.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

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:

Source study has reliability 1. Details on the read across are available in section 13.

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

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: DR. K. Thomae GmbH, D-7950 Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: mean 181 g (males), 174 g (females)
- Fasting period before study: at least 16 h, with water ad libitum
- Housing: single housing in stainless steel wire mesh cages, Type DLK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod: 12/12 (hrs dark / hrs light)

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

- Concentration of test material in vehicle: 11%
- Amount of vehicle (if gavage): 20 ml/kg bw
- Justification for choice of vehicle: aquous formulation corrresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg bw

Doses:

2200 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 day
- Frequency of observations and weighing: recording of signs and symptomps several times on the day of administration, at least once each workday; individually body weights shortly before application (day 0), and on days 7 and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: Feces of male and female animals were black discoloured. Males additionally exhibited piloerection and black smeared fur in the anogenital area.

Gross pathology:

No pathological findings.

Other findings:

Symptoms after administration of 2200 mg/kg bw of test material in vehicle by gavage:
- Males:
Day 1 - day 2: piloerection (2/3 animals)
Hour 4 - day 2: discoloured feces (black) (3/3 animals)
Hour 4 - day 3: black smeared fur in the anogenital area (2/3 animals)

- Females:
Hour 1 - day 1: discoloured feces (black) (3/3 animals)

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rat, oral) > 2200 mg/kg bw.

Executive summary:

Method:

Acute oral toxicity in rats was assessed following OECD guideline 401. A dose of 2200 mg/kg bw was administered by gavage 3 rats/sex. A 14-days observation period followed dosing.

Results:

No mortality was recorded, thus LD₅₀ > 2200 mg/kg. Black discoloured feces were noted in both males and females; in males piloerection was also noted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data on target substance was available, thus a read across approach was followed, as detailed in section 13. Available data on Similar Substance 01 was used.

Acute oral toxicity of test substance was investigated in 2 studies, both well-documented and reliable. The most recent study was selected as key study.

In a study from 1993, groups of 3 rats/sex were tested according to OECD guideline 401, upon administration of a limit dose of 2200 mg/kg bw by gavage. Clinical signs were discoloured feces for male and female rats and piloerection and smeared fur in the anogenital area in male animals. No mortality or gross pathological changes were reported.

In a study from 1984 according to OECD guideline 401, two groups of 5 rats/sex were dosed with a limit dose of 5000 mg/kg bw by gavage. Clinical signs were black feces for male and female rats. No mortality or gross pathological changes were reported.

 

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).