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Description of key information

The median lethal dose (LD50) of test item (Pigment Red 122) after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight.

No mortality was observed after nose-only inhalation exposure to the test item (Pigment Red 122) of male and female rats at the highest technically achievable aerosol concentration of 3.055 mg/L for 4 hours. Based on the lack of lethal effects, severe clinical symptoms indicating a life-threatening or moribund state, and gross morphological abnormalities, it may be reasonably assumed that the LC50 for the test item is greater than 5 mg/l air.

Pigment Red 122 caused no mortality in male and female rabbits after a single dermal application of 3000 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:
22 June 2005 to 11 August 2005
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
GLP compliance:
yes (incl. QA statement)
Remarks:
Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain specifics: HanRcc:WIST (SPF)
- Source: RCC Ltd, Laboratory Animal services, Füllinsdorf, Switzerland
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 173.8-192.2 g on day 1 (treatment)
- Fasting period before study: approximately 18 hours before treatment, access to water permitted)
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): standard rat/mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg body weight (volume of test item in vehicle)
- Justification for choice of vehicle: solubility trial before the study initiation date (excluded from GLP statement of compliance)
- Vehicle Lot/batch no. (if required): 1107712 24104041
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 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, 3 and 5 h after administration on day 1 and twice daily on days 2-15
clinical signs: during the first 30 minutes and approximately 1, 2, 3 and 5 h after administration on day 1 and 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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths
Clinical signs:
other: Red faeces in all animals from test day 2 to 5 (3 animals) or 6 (3 animals), slightly ruffled fur in 3/6 animals from 30 minutes until 2, 3 or 5 hours (different duration in each of the affected animals) after treatment on day 1.
Gross pathology:
Congestion of the lungs in one animal, but no macroscopic findings in the remaining five animals at scheduled necropsy.
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP regulation
Conclusions:
The median lethal dose (LD50) of test item (Pigment Red 122) after a single oral administration to female rats, observed over a period of 14 days, was greater than 2000 mg/kg body weight.
Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with the test item (Pigment Red 122) by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL 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, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality / viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice 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.

Red feces were observed in all animals from test day 2 to 5 or test day 6. Three out of 6 animals were noted with slightly ruffled fur from the observation performed within the first 30 minutes after application to the 2-, 3- or 5 -hour reading.

The body weight of the animals was within the range commonly recorded for this strain and age.

Congestion of the lungs was noted in one animal whereas no macroscopic findings were recorded in the remaining five animals at scheduled necropsy.

The median lethal dose of the test item after single oral administration to female rats, observed over a period of 14 days is:

LD50 (female rat): greater than 2000 mg/kg body weight

Therefore, the test item has not to be classified as acutely toxic by the oral route 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:
reliable

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 January 2007 to 16 March 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Test data for Registration of Agricultural Chemicals, Test Guidelines, Acute Inhalation Toxicity, 12 NohSan No. 8147, November 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Study in compliance with Swiss Ordinance relating to GLP, which is based on OECD Principles of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain specifics: HanBrl:WIST(SPF)
- Source: RCC Ltd, Laboratory Animal Services, Füllinsdorf, Switzerland
- Age at study initiation: males: 9 weeks, females: 10 weeks
- Weight at study initiation: males: 232.1-261.6 g, females: 210.0-221.9 g
- Housing: Animals of the same sex were housed in groups of five in Makrolon type IV cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): standard rat maintenance diet, ad libitum, except during the treatment period
- Water (e.g. ad libitum): community tap water ad libitum, except during the treatment period
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20 °C
- Humidity (%): 30-72%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Remarks:
flow-past exposure
Vehicle:
other: unchanged (no vehicle)
Mass median aerodynamic diameter (MMAD):
>= 2.64 - <= 2.83 µm
Geometric standard deviation (GSD):
>= 3.93 - <= 4.04
Remark on MMAD/GSD:
MMAD (two measurements)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Similar to the system originally described by Sachsse et al. (1973, 1976) and Cannon et al. (1983)
- Method of holding animals in test chamber: restraint tubes
- Source and rate of air: total airflow: 34 l/min, airflow of the aerosol arriving at the animal ports: 1 l/min per animal port
- System of generating particulates/aerosols: dust aerosol generated from the test item using a rotating brush aerosol generator connected to a micronising jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutraliser.
- Method of particle size determination: gravimetrically (see below)
- Temperature, humidity, oxygen concentration in air chamber: measured on test atmosphere samples collected from the feed tubes in the breathing zone of the animals

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric (weighing the generator cylinder containing the test item before and after the exposure to determine the quantity of test item used. The total weight used during the exposure was then divided by the total airflow volume to give the nominal concentration.
- Samples taken from breathing zone: yes (gravimetric using Millipore filters)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: measured gravimetrically twice during each exposure using a 7 stage cascade a Mercer Impactor
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): calculated on the basis of the results with the Mercer Impactor
For results, see below

References:
Sachsse, K., L. Ullmann, G. Voss and R. Hess: Measurements of Inhalation Toxicity of Aerosols in Small Laboratory Animals. In: Proceedings of the Europ. Soc. for the Study of Drug Toxicity, Vol. XV, pp. 239-251, Zürich, June 1973.
Sachsse, K., L. Ullmann, K. Zbinden: Toxikologische Prüfungen von Aerosolen im Tierexperiment, "Chemische Rundschau" 29 (1976), No. 38, p. 1.
Cannon, W.C., E.F. Blanton and K.E. McDonald: The Flow-Past Chamber: An Improved Nose-Only Exposure System for Rodents, Am. Ind. Hyg. Assoc. J., 44 (12): 923-928, 1983
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see above
Duration of exposure:
4 h
Remarks on duration:
Approx. 2 h after the start, exposure was interrupted for 3 min (cleaning the exposure system and changing the piston cylinder). Nevertheless, animals were exposed for a total of 4 hours.
Concentrations:
Nominal concentration: 4.419 mg/l
Actual concentration: 3.055 mg/l (± 0.068 mg/l, n = 5), MMAD (two measurements): 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93)
Rationale: A target concentration of 3 mg/l air (actual concentration of test item in air) corresponds to the maximum technically feasible aerosol concentration as determined in technical trials.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days beginning on the day of exposure
- Frequency of observations and weighing: daily for mortality and clinical signs, weiging on days 1 (before exposure), 4, 8 and 15 (day of necropsy)
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed:
clinical signs included, but were not limited to: changes in behaviour, somatomotor activity, body position, respiratory and circulatory effects, autonomic effects such as salivation, central nervous system effects, e.g. tremors or convulsions, reactivity to handling or sensory stimuli, altered strength, alteration of the skin, fur, nose, eyes and mucous membranes
Statistics:
The LOGIT model was not used as only one group was exposed.
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
3.055 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: mean analytical concentration of five measurements
Mortality:
No mortality, all animals were sacrificed as scheduled on test day 15.
Clinical signs:
other: All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent. These signs were not noted from day 4 onwards.
Body weight:
Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.
Gross pathology:
There were no macroscopic pathology findings in any of the animals. No macroscopically visible coloration of the lungs by Hostaperm Rosa E was detected.
Other findings:
Temperature, relative humidity and oxygen concentration during exposure were considered to be satisfactory for this type of study.
Interpretation of results:
GHS criteria not met
Conclusions:
No mortality was observed after nose-only inhalation exposure to the test item (Pigment Red 122) of male and female rats at the highest technically achievable aerosol concentration of 3.055 mg/L for 4 hours. Based on the lack of lethal effects, severe clinical symptoms indicating a life-threatening or moribund state, and gross morphological abnormalities, it may be reasonably assumed that the LC50 for the test item is greater than 5 mg/l air and that the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.
Executive summary:

The purpose of this study was to assess the acute inhalation toxicity of the test item when administered to rats for a single 4-hour period.

One group of five male and five female albino rats [HanBrl:WIST(SPF)], was exposed by nose-only, flow-past inhalation to the test item at mean aerosol concentrations of 3.055 ± 0.068 (n=5) mg/L air (gravimetrically determined). Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters and geometric standard deviations (GSD) of 2.83 µm (GSD 4.04) and 2.64 µm (GSD 3.93), respectively.

All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. All animals were sacrificed and necropsied on day 15.

The ranges of temperature, relative humidity, oxygen content and particle size measured during the exposure were satisfactory for a study of this type.

There were no spontaneous deaths.

All animals showed rales, decreased spontaneous activity, hunched posture, tachypnea and ruffled fur on the day of exposure and the two following days in individually variable extent.

Four females showed a slight transient body weight loss between Day 1 and Day 4. All other animals gained body weight as expected.

There were no macroscopic pathology findings in any of the animals.

In conclusion, at the highest technically achievable aerosol concentration of the test item of 3.055 mg/L air, none of the ten exposed animals died (LC0 = 3.055 mg/L). Based on the lack of lethal effects or severe clinical symptoms indicating a life-threatening or moribund state, it may be reasonably assumed that the LC50 for the test item is likely to be greater than 5 mg/L air.

Therefore, the test item has not to be classified as acutely toxic by the inhalation route according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
3 050 mg/m³ air
Quality of whole database:
reliable

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint:
acute toxicity: dermal
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: secondary source
GLP compliance:
not specified
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
not specified
Vehicle:
water
Duration of exposure:
24 h
Doses:
3 g/kg of the test article (in the form of an aqueous slurry)
No. of animals per sex per dose:
2 males and 2 females
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Remarks on result:
other: no animals died within the 14 day observation period

No mortality was observed at 3 g/kg and no unusual behavioral, systemic reactions or gross pathologic alterations were observed. Body weight gains were within normal range of growth.

Conclusions:
Pigment Red 122 caused no mortality in male and female rabbits after a single dermal application of 3000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw

Additional information

Justification for classification or non-classification

no classification

Neither in studies witn oral nor inhaltion nor dermal exposure any adverse effects were observed at / above limit doses.