Reactive Orange 143

Endpoint summary

Description of key information

The median lethal dose (LD50) in an acute oral and acute dermal toxiciy study was >2000 mg/kg bw. 

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:

14 December 2011 to 03 January 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Identification FAT 40854/A TE
Description Reddish-brown powder (determined at NOTOX)
Batch TZ 5719 / BOP 02-11
Content 46.2 % (4 main constituents)
Test substance storage At room temperature in the dark
Stability under storage conditions Stable
Expiry date 01 April 2016
Stability in vehicle (Water): Stability for at least 6 hours at room temperature
Solubility in vehicle: More than 80 g/L in Water

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within ± 20 % of the sex mean.
- Fasting period before study:
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.7
- Humidity (%):42 – 62
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 December 2011 - 03 January 2012

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE: Water
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Hunched posture was noted in all animals on Day 1. In addition all animals showed red faeces on Day 1 or 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of FAT 40854/A in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Executive summary:

In a GLP-compliant study, assessment of acute oral toxicity with FAT 40854/A in the rat using acute toxic class method) was carried out according to OECD No.423 (and EU method B1 tris. FAT 40854/A was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. The substance was diluted in water and an application volume of 10 mL/kg was used. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Hunched posture was noted in all animals on Day 1. In addition all animals showed red faeces on Day 1 or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of FAT 40854/A in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline and GLP-compliant study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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:

key study

Study period:

18 January to 01 February 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Identification FAT 40854/A TE
Description Reddish-brown powder (determined at NOTOX)
Batch TZ 5719 / BOP 02-11
Content 46.2 % (4 main constituents)
Test substance storage At room temperature in the dark
Stability under storage conditions Stable
Expiry date 01 April 2016
Hygroscopic: Yes, store in well-sealed container
Volatile: No
pH 5.4 at concentration of >80 g/L
Stability in Water: Stability for at least 6 hours at room temperature
Solubility in vehicle: Water: greater than 80 g/L

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within ± 20 % of the sex mean.
- Housing: Individual housing in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 23.5
- Humidity (%): 36 – 66
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 18 January - 01 February 2012

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped. The formulation was applied in an area of approx. 10 % of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Dose level (volume): 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. No correction was made for purity of the test substance.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

None.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Chromodacryorrhoea, was noted in one male and two females on Day 1. Scales on the snout was noted in one male. Redness, scales and/or scabs were seen in the treated skin-area of all animals during the observation period.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal median lethal dose (LD50) of FAT 40854/A in Wistar rats was >2000 mg/kg body weight.

Executive summary:

In a GLP-compliant study, assessment of acute dermal toxicity with FAT 40854/A in the rat was carried according to OECD No.402 and EU method B3. FAT 40854/A was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. The substance was diluted in water and the volume of application was 10 mg/kg. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea was noted in one male and two females on Day 1. Scales on the snout was noted in one male. Redness, scales and/or scabs were seen in the treated skin-area of all animals during the observation period. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal median lethal dose (LD50) of FAT 40854/A in Wistar rats was >2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline and GLP-compliant study

Additional information

Acute Oral toxicity:

In a GLP-compliant study, assessment of acute oral toxicity with FAT 40854/A in the rat using acute toxic class method) was carried out according to OECD No.423 (and EU method B1 tris. FAT 40854/A was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. The substance was diluted in water and an application volume of 10 mL/kg was used. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Hunched posture was noted in all animals on Day 1. In addition all animals showed red faeces on Day 1 or 2. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of FAT 40854/A in Wistar rats was established to exceed 2000 mg/kg bodyweight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

 

Acute inhalation toxicity:

Currently no study to assess acute inhalation toxicity of Reactive Orange 143 is available. However, based on low vapour pressure (<1.5 x 10 ^-3) the substance is considered to have low volatility. Synthesis and formulation of this chemical is performed in a closed process; the final product consists of liquid formulations only. Hence, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a liquid formulation, the exposure via inhalation is unlikely. Further, Reactive Orange 143 was found to be miscible in water (water solubility >500 g/L) and have low log partition coefficient (<-1.8), hence, in the case of dust of the substance entering the respiratory tract, it will be trapped in the mucus and cleared thereby further limiting the absorption. The chemical showed low toxicity potential (LD50 >2000 mg/kg bw) in the available acute oral and dermal toxicity studies with no mortality or systemic toxicity, hence it does not need to be classified as STOT SE. Taking the above arguments into account, low toxicity potential is expected on acute exposure of Reactive Orange 143 via inhalation route and hence testing by the inhalation route was considered scientifically not necessary.

Acute dermal toxicity:

In a GLP-compliant study, assessment of acute dermal toxicity with FAT 40854/A in the rat was carried according to OECD No.402 and EU method B3. FAT 40854/A was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. The substance was diluted in water and the volume of application was 10 mg/kg. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea was noted in one male and two females on Day 1. Scales on the snout was noted in one male. Redness, scales and/or scabs were seen in the treated skin-area of all animals during the observation period. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal median lethal dose (LD50) of FAT 40854/A in Wistar rats was >2000 mg/kg body weight.

Justification for classification or non-classification

Based on the observed acute median lethal dose (LD₅₀) of >2000 mg/kg bw in the acute oral and dermal toxicity study, the test substance is not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.