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Diss Factsheets

Administrative data

Description of key information

RA_PR 53:1_key_401_1993_Hoechst_93.0643: LD50: >2000 mg/kg body weight, no specific target organ toxicity
QSAR PR 50.1 acute oral toxicity OECD Toolbox: LD50: 4840 mg/kg body weight
QSAR PR 53.1 acute oral toxicity OECD Toolbox: LD50: 6670 mg/kg body weight

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
According to OECD and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
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
- Strain specifics: Hoe: WISKf (SPF71)
- Source: Hoechst AG, SPF breeding colony
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: male 178 g - 183 g (mean 181 g), female 177 g - 186 g (mean 182 g) on day 1 (treatment)
- Fasting period before study: from 16 hours before to 3 - 4 hours after treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet: standard rat diet (Altromin 1324) ad libitum
- Water: tap water in plastic bottles ad libitum
- Acclimation period: not necessary (breeding at identical conditions)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 55 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % (w/v)
- Amount of vehicle (if gavage): 10 mL/kg body weight (test item in vehicle administered)
- Purity: Oleum Sesami Ph. Eur. III, Mainland Pharmazeutische Fabrik GmbH, Frankfurt
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days starting with treatment day 1
- Frequency of observations and weighing:
- mortality/viability: during the first 30 minutes and approximately 1, 2, 4 and 6 h after administration on day 1 and twice daily (weekends and public holidays once daily) on days 2-15
- clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 6 h after administration on day 1 and twice daily (weekends and public
holidays once daily) on days 2-15
- body weights: on days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination
Statistics:
None
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no deaths occured during the whole study
Clinical signs:
other: the animals showed sunken flanks, stilted gait and squatting posture. All clinical signs of intoxication were reversible one day after application. Red coloured feces were observed one day after application
Gross pathology:
No macroscopic findings at scheduled necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Single application of 2000 mg/kg bw of the test substance did not cause lethality in male and female Wistar rats during the 14 day observation period, resulting in a LD50 > 2000 mg/kg bw.
Executive summary:

One group of five male HoeWISK (SPF71) rats and one group of five female HoeWISK (SPF71) rats were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (sesame oil) at a concentration of 20 % (w/v) and administered at a volume dosage of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 4 and 6 hours after treatment on day 1 and twice daily (weekends and public holidays once daily) during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 4 and 6 hours after administration on test day 1 (with the clinical signs) and twice daily (weekends and public holidays once daily) during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

The animlas showed sunken flanks, stilted gait and squatting posture. All clinical signs of intoxication were reversible within one day after applikation

Development of body weight was not impaired.

No macroscopic findings were recorded for the animals at scheduled necropsy.

Therefore, the test substance has not to be classified as acutely toxic or as STOT SE according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Data pool used for derivation of the LD50 value above 2000 mg/kg bw is of adequate reliability.

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

Discussion

No experimatal data are available for acute oral toxicity of Pigment Red 50:1. Thus data were provided by application of read across using existing data from Pigment Red 53.1 to predict acute oral toxicity of Pigment Red 50:1. The prediction for Pigment Red 50:1 reads as follows:

LD50: > 2000 mg/kg body weight

No specific target organ toxicity

This derivation is strongly supported by QSAR analyses using the OECD Toolbox which predicts the following acute oral toxicity:

Pigment Red 50:1, LD50: 4840 mg/kg body weight

Pigment Red 53.1, LD50: 6670 mg/kg body weight

The data sources used provide consistent data allowing the final conclusion that the median lethal oral dose of Pigment Red 50:1 is above 2000 mg/kg body weight and that Pigment Red 50:1 causes no specific target organ toxicity after single exposure.

Read Across Justification

The purpose of this assessment is to provide justification for read across in order to estimate acute oral toxicity of Pigment Red 50:1 (target substance) and to predict its possible irritant or corrosive properties after contact with skin or eyes based on existing date coming from Pigment Red 53:1 (source substance).

The pigments used in this approach are structurally similar and differ only by diverging substituents in the common core molecule. Target and source substance are solids which decompose at high temperatures (>= 306°C). Solubility in water or n-octanol is low or very low for the source substance (in water: 3.0 mg/L, in n-Octanol: 0.7 mg/L) and even lower for the target substance (in water: 0.3 mg/L, in n-Octanol: 0.6 mg/L). These values suggest poor absorption and low bioavailability for both pigments.

The log n-octanol-water partition coefficients were -0.62 and 0.41 for the source and for the target substance respectively. These values are far below the limit of concern considered to be critical for bio-accumulative properties.

The pH value of both pigments is not extreme and therefore gives no reason to assume corrosive properties.

Pigment Red 50:1 showed very limited biodegradability (not readily biodegradable in the 10-day-window and within 28 days), which is assumed to be due to its unavailability for microorganisms.

Poor bioavailability is probably also the reason for the absence of any relevant acute mammalian toxicity. The target pigment was not skin sensitising in the LLNA. Both pigments were not mutagenic in the Bacterial Reverse Mutation Assay neither with nor without S9-mix indicating that metabolic activation is not an issue.

Due to its low solubility and its inertness it can reasonably be assumed that considerable amounts of both pigments are virtually not present in a dissolved form on the skin or mucous membranes after single dermal or oral exposure, i.e. they cannot be absorbed in relevant amounts after single oral application and do not cause local effects after contact with skin or eyes. This reasoning is supported by the outcome of QSAR analyses predicting very low acute oral toxicity (LD50 values above 4000 mg/kg bw.) and the absence of skin and eye irritating properties for both the target and the source substance.

This assessment is based on experimental and QSAR data on the source pigment as compared to available data of the target pigment covering the following endpoints: Specific physicochemical properties, acute oral toxicity, skin and eye irritation/corrosion, skin sensitisation, genotoxicity in vitro, and biodegradability (for details see data matrix below).

In conclusion, the similar structure and the uniformity of physicochemical, environmental fate and toxicological properties justifies the application of read across to predict the outcome of acute oral toxicity and skin/eye irritation/corrosion studies of the target pigment based on existing date coming from the source pigment. Supporting evidence is provided by QSAR analysis predicting consistently a very low acute oral toxicity and the absence of irritating/corrosive properties to skin and eyes.

Data Matrix

CHEMICAL NAME

C.I. Pigment Red 50:1

C.I. Pigment Red 53:1

Role

Target Substance

Source Substance

CAS No.

6372-81-2

5160-02-1

Physical and Chemical Properties

Physical state of the substance at 20° C and 1013 hPa

red solid

red solid

Melting/freezing point

Decomp. Temp.:
>=306°C

Decomp. Temp.:
> 320°C

Water solubility

0.25 mg/L

2.986 mg/L

n-Octanol solubility

0.64 mg/L

0.716

log Partition coefficient
n-octanol/water (logPow)

0.41

-0.62

pH

6.9
(10% suspension)

5 - 8

Environmental Fate and Pathways

Biodegradation in water: screening test

not readily biodegradable

in the 10-d-window and after 28 days

no experimental data

Toxicological Information

Skin irritation (in vivo)

RA-conclusion:
not irritating

not irritating

Skin irritation (QSAR)

OECD Toolbox:
not irritating

OECD Toolbox:
not irritating

Eye irritation (in vivo)

RA-conclusion:
not irritating

not irritating

Eye irritation (QSAR)

OECD Toolbox:
not irritating

OECD Toolbox:
not irritating

Skin sensitisation

not skin sensitising
(LLNA)

no experimental data

In vitro gene mutation study in bacteria

not mutagenic
(AMES)

not mutagenic
(AMES)

Acute toxicity, oral route, (experimental LD50 mg/kg b.w., rats)

RA-conclusion:
> 2000

> 2000

Acute toxicity, oral route (QSAR, LD50 mg/kg b.w.)

OECD Toolbox:
4840

OECD Toolbox:
6670



Justification for selection of acute toxicity – oral endpoint
Eperimental data for read across come from the most similar substance available.

Justification for classification or non-classification

Based on available data an LD50 of greater than 2000 mg/kg bw was derived by read across and QSAR analyses. This value is above the threshold for classification. Also absence of specific target organ toxicity was predicted. Therefore the test item has not to be classified for acute oral toxicity or STOT SE according to Regulation (EC) No 1272/2008.