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Administrative data

Description of key information

Acute oral toxicity:
The test item (Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single oral gavage


Administration to male and female rats at 5000 mg/kg bw in a OECD guideline and GLP compliant study.


The LD50 (male/female rat) was greater than 5000 mg/kg body weight (Hoechst, 1983). This key study is supported by further


acute oral toxicity studies with Pigment Red 112 in which no lethal or other severe effects were reported at the highest dose tested of 10,000 mg/kg (Hoechst, 1979a; 1979b; Ciba-Geigy, 1972) or 15,000 mg/kg (Reseach Institute for Organic Syntheses, 2007).
Acute dermal toxicity:
The test item (preparation containing Pigment Red 112 at >90%) did not cause any mortality or significant clinical signs or necropsy findings after single dermal application to male rats at 5000 mg/kg bw in a OECD guideline compliant study. The LD50 (male rat) was greater than 5000 mg/kg body weight.
Acute inhalation toxicity:
Study was waived; substance is not classified for this endpoint. When aerosolized in respirable form, the substance is considered likely to behave like an inert dust.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline 401 and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
EEC Directive 79-831 Annex V, Part B 4.1.1.
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, Kastengrund, SPF-breed
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: male 191 g - 199 g, female 187 g - 208 g
- Fasting period before study: approximately 16 hours before treatment, access to water permitted
- Housing: in groups of five in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): standard rat diet (Albtromin 1324) ad libidum
- Water (e.g. ad libitum): tap water ad libidum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 55 ± 10 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 20 ml/kg body weight, application volume was distributed over one hour (test item in vehicle administered)
Doses:
5000 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, and 4 h after administration on day 1 and 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 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:
> 5 000 mg/kg bw
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no deaths
Clinical signs:
During the first hours reduced spontaneous activity, and after 2-4 hours hunched posture and diarrhea with stained feces were observed. No clinical signs were noted at 1 day after administration or later.
Body weight:
male: increase of body weight after 14 days 43-51%
female: increase of body weight after 14 days 14-26%
Gross pathology:
No macroscopic findings at scheduled necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
1272/2008/EC: Acute oral toxicity: no classification warranted

The test item (Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single oral gavage administration to male and female rats at 5000 mg/kg bw in a OECD guideline and GLP compliant study. The LD50 (male/female rat) was greater than 5000 mg/kg body weight.
Executive summary:

The test item (Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single oral gavage administration to male and female rats at 5000 mg/kg bw in a OECD guideline and GLP compliant study. The LD50 (male/female rat) was greater than 5000 mg/kg body weight (Hoechst, 1983).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test performed before OECD and GLP guidelines. Important aspects (14 day-postobservation time) in line with current OECD guidelines.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
other: 2% starch in water
Doses:
10000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Conclusions:
67/548/EEC: Acute oral toxicity: no classification warranted
1272/2008/EC: Acute oral toxicity: no classification warranted

The test item (Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single oral gavage administration to female rats at 10000 mg/kg bw in a study performed similar to the OECD 401 guideline. The LD50 (female rat) was greater than 10000 mg/kg body weight.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test performed before OECD and GLP guidelines. Important aspects (14 day-postobservation time) in line with current OECD guidelines.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Route of administration:
oral: gavage
Vehicle:
other: 2% starch in water
Doses:
10000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Conclusions:
67/548/EEC: Acute oral toxicity: no classification warranted
1272/2008/EC: Acute oral toxicity: no classification warranted

The test item (Pigment Red 112) did not cause any mortality or clinical signs or necropsy findings after single oral gavage administration to female rats at 10000 mg/kg bw in a study performed similar to the OECD 401 guideline. The LD50 (female rat) was greater than 10000 mg/kg body weight.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test performed before OECD and GLP guidelines. Important aspects (recording of symptoms, mortality and body weight) in line with current OECD guidelines, the shorter postobservation period (8 vs. 14 days) is considered acceptable because higher doses (up to 10000 mg/kg) than today's limit dose (2000 mg/kg) were used.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
pre-GLP study
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CFE (RAC, SPF)
Sex:
male/female
Route of administration:
oral: gavage
Doses:
5000 and 10000 mg/kg bw
No. of animals per sex per dose:
3-5 male and 2-5 female rats
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Conclusions:
67/548/EEC: Acute oral toxicity: no classification warranted
1272/2008/EC: Acute oral toxicity: no classification warranted

The test item (Pigment Red 112) did not cause any mortality or clinical signs or necropsy findings after single oral gavage administration to male and female rats at up to 10000 mg/kg bw in a study performed similar to the OECD 401 guideline. The LD50 (female rat) was greater than 10000 mg/kg body weight.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Oct-Dec 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test was performed in accordance with OECD, but not according to GLP guidelines and the English test report was reconstructed by the test institute from the study raw data and the original Czech report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
olive oil
Doses:
2500, 5000, 10000 and 15000 mg/kg bw in orientation study;
15000 mg/kg bw in main study
No. of animals per sex per dose:
3 females/dose in orientation study, 10 males and 10 females in main study
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Conclusions:
67/548/EEC: Acute oral toxicity: no classification warranted
1272/2008/EC: Acute oral toxicity: no classification warranted

The Test item (<90% Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single oral gavage administration to female rats at 15000 mg/kg bw in a study performed according to the OECD 401 guideline. The LD50 (male and female rat) was greater than 15000 mg/kg body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
reliable

Acute toxicity: via inhalation route

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:
11 October - 12 November 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test was performed in accordance with OECD, but not according to GLP guidelines and the English test report was reconstructed by the test institute from the study raw data and the original Czech report.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Breeding Farm VELAZ, monitoring quality
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 225-275 g
- Fasting period before study: not stated
- Housing: 5 animals per plastic breeding cage VELAZ T4
- Diet (e.g. ad libitum): ST 1 Bergman - standard pellet diet ad libitum, Mill Kocanda, Jesenice u Prahy, Czech Republic
- Water (e.g. ad libitum): dinking tap water ad libitum
- Acclimation period: minumum 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 3°C (air-condition)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 4x6 cm (shaved 24 hours before application)
- Type of wrap if used: application site was covered by mull, plastic foil and held in contact by plaster (strapping)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 24-hour application period, the remains of the test substance were removed from the skin
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): water was used to moisten test substance
Duration of exposure:
24 hours
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 males
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical examination was done after 30 min, 3 hours of the 1st day, in the moring and afternoon of the second day and thereafter daily for 14 days; body weights were recorded before application, atday 8 and before euthanasia of animals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight:
Statistics:
not relevant
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 14-day observation period.
Clinical signs:
No clinical signs were observed during the 14-day observation period.
Body weight:
Body weight developments were within the physiological range.
Gross pathology:
All animals were without gross morphological alterations.
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
1272/2008/EC: Acute oral toxicity: no classification warranted

The Test item (<90% Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single dermal application to male rats at 5000 mg/kg bw in a OECD guideline compliant study. The LD50 (male rat) was greater than 5000 mg/kg body weight.
Executive summary:

The Test item (<90% Pigment Red 112) did not cause any mortality or significant clinical signs or necropsy findings after single dermal application to male rats at 5000 mg/kg bw in a OECD guideline compliant study. The LD50 (male rat) was greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
reliable

Additional information

- it is unlikely that Pigment Red 112 becomes systemically bioavailable after skin contact due to its extremely low solubility in water and n-octanol.


 


 

Justification for classification or non-classification

Due to the findings described above (LD50 oral in rats >2000 mg/kg bw) Pigment Red 112 is not classified as acute orally toxic according to the criteria laid down in the EU Classification Labelling and Packaging Regulation (1272/2008/EC).

 

It can reasonably be deduced that Pigment Red 112 does not exert systemic toxic effects after acute inhalation exposure and thus does not have to be classified according to the criteria laid down in the EU Dangerous Substances Directive (67/548/) and in the EU Classification Labelling and Packaging Regulation (1272/2008/EC), because

- Pigment Red 112 did not cause lethal effects after administration of a single oral dose of up to 15,000 mg/kg in rats,

- Pigment Red 112 does not have to be classified as skin irritating, and

- it is unlikely that Pigment Red 112 becomes systemically bioavailable after inhalation due to its extremely low solubility in water and n-octanol.

Therefore, it is concluded that Pigment Red 112, when aerosolized, is an inert dust and that testing is not scientifically necessary.

 

Furthermore, Pigment Red 112 does not have to be classified for specific target organ toxicity – single exposure according to Regulation (EC) No 1272/2008, as no specific toxic effects were observed after acute exposure.