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Description of key information

Oral LD50 values for Diarylide Yellow Pigment 12 are > 2000 mg/kg bw, the limit for classification. No lethality was observed after acute inhalation exposure to the maximum technically feasible test concentration of 4.3 mg/L Pigment Yellow 13 (structural analogue)


No lethality was observed after single dermal application of 1710 mg/kg bw Pigment Yellow 13 (structural analogue).

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:
From 4 JULY 1983 to 1 AUG 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study (OECD TG 401)
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
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 specification: Hoe: WISKf (SPF71)
- Source: Hoechst AG, Kastengrund, SPF-breeding
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: male mean: 187,2 g; female mean: 207,3 g
- Fasting period before study: 16 h
- Housing: 5 animals per Macrolon cage
- Diet: Altromin 1324 (Altromin-GmbH, Lage/Lippe, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12,5% w/v

MAXIMUM DOSE VOLUME APPLIED: 40 ml/kg bw
Calculated dose volume was divided into two equal fractions and applied in a one hour interval.

DOSAGE PREPARATION: test substance was suspended in vehicle
Doses:
male: 5000 mg/kg bw
female: 5000, 4000, 3150 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 weighing: once per week
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination
Statistics:
Probit analysis: according to method of Lindner and Weber
95% confidence interval: according to method of Fieller and Sidak
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 228 mg/kg bw
Remarks on result:
other: The test item contained only 47% of the submission substance, i.e. LD 50 of 4740 mg test item / kg bw corresponds to 2228 mg submission substance/kg bw.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 350 mg/kg bw
Remarks on result:
other: No males died within the observation period. The test item contained only 47% of the submission substance, i.e. LD 50 of > 5000 mg test item / kg bw corresponds to 2350 mg submission substance/kg bw.
Mortality:
males: none of the tested animals died within the observation period
females:
- 5000 mg/kg bw: 3/5
- 4000 mg/kg bw: 1/5
- 3150 mg/kg bw: 0/5
The animals died within the first three days after application.
Clinical signs:
other: males: On the day of application the animals showed a reduced spontaneous activity, one male showed spread legs and three males a crouched posture. All animals had yellow-coloured faeces on day 1 and 2 and yellow coloured skin on days 1-3. From day four
Gross pathology:
male:
- 5000 mg/kg bw: no macroscopic anomalies found
female:
- 3150 mg/kg bw: no macroscopic anomalies found
- 4000 mg/kg bw: 4 animals had no macroscopic anomalies
The one animal which died during the test was eroded.
- 5000 mg/kg bw: 2 animals sacrificed at the end of the postexposure period had no macroscopic anomalies
3 animals died during the observation period:
- stomach was tightly filled with air and test substance
- intestinal tract was filled with test substance
- pancreas was rosy-coloured
- in two out of this three animals the lung and the adrenal gland were dark-coloured
- one out of the three animals displayed bright foci on the liver
Interpretation of results:
GHS criteria not met
Remarks:
Regulation (EC) no 1272/2008
Conclusions:
The testing for acute oral toxicity according OECD TG 401 yielded a median lethal dose (LD50) of 4740 mg test item/kg bw (corresponding to 2228 mg P.Y. 12/kg bw) in female Wistar-rats. The testing in male rats revealed no obvious toxicity in the tested dose, thus leading to a LD50 > 5000 mg/kg bw (corresponding to > 2350 mg Permanent-Gelb DHG/kg bw).
The test was performed with Permanent-Gelb DHG-80 which contains relevant amounts of Permanent-Gelb DHG, which is identical to the submission substance. Therefore the test results are considered adequate to fulfill the endpoint requirements.
Executive summary:

Acute oral toxicity of the test item was tested in male and female Wistar rats according to OECD TG 401. Administered dose levels were 3150, 4000 and 5000 mg/kg bw in female and 5000 mg/kg bw in male rats. Three females in the highest dose level and one female in the middle dose level died within 3 days after application. An oral LD50 of 4740 mg test item/kg bw (corresponding to 2228 mg P.Y. 12/kg bw) has been calculated. No lethality was observed in male rats.

Therefore, the test item has not to be classified for acute toxicity according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 228 mg/kg bw
Quality of whole database:
reliable without restriction

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
: 10 hrs light cycle, some exposure data are missing (e.g. MMAD (not calculated), equilibration period)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: in house breeding, SPF breeding colony
- Weight at study initiation: 170 - 190 g
- Housing: in Macrolon cages (type 4) in groups of 10, males and females separated
- Diet: NAFAG (Gossau SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 4 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-1
- Humidity (%): 55+/-5
- Photoperiod: 10 hrs light cycle day
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: inhalation cylinder
- Method of holding animals in test chamber: seperate PVC tubes
- System of generating aerosols: Injecting the solid material with the help of "Grafix Exactometer injector" into an air stream which was discharged into the exposure chamber through a nozzle under a pressure of 2 atm. at a rate of 20 L/min.
- Method of particle size determination: gravimetrically
- Temperature, humidity, oxygen: 24 °C, 38%, 20 Vol.%

TEST ATMOSPHERE
- Brief description of analytical method used: Concentration was determined gravimetrically by sampling the test atmosphere through a selectron filter of 50 mm diameter and with a pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 10 L/min. The size distribution of the particles was measured with a Cascade Impactor with selectron filters of 25 mm diameter and with pore size of 0.2 µm (Schleicher and Schuell, Feldbach, Switzerland) at an air flow rate of 17.5 L/min.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: < 1 µm to > 7 µm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not calculated
Analytical verification of test atmosphere concentrations:
yes
Remarks:
: gravimetric measurement
Duration of exposure:
4 h
Concentrations:
4250 (+/-128) mg/m³
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 250 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no death occurred
Clinical signs:
other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days
Gross pathology:
- no macroscopically visible changes were found
Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of male and female rats to 4250 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4250 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 250 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: no animals died within the 14 day observation period
Mortality:
- no death occurred
Clinical signs:
other: - within 3 to 4 hours after starting the exposure period rats showed dyspnoea, curved or ventral position and ruffled fur - recovery within 4 days
Gross pathology:
- no macroscopically visible changes were found
Interpretation of results:
GHS criteria not met
Conclusions:
Exposure of male and female rats to 4250 mg/m³ test item for 4 hours did not result in the death of the animals during a 14 day observation period, resulting in a LC50 value of > 4250 mg/m³.
Executive summary:

Acute inhalation toxicity of the test item has been investigated in male and female Tif: RAIf (SPF) rats (10 per sex). They were exposed to 4250 mg test substance per cubic meter for 4 h (maximal applicable dose). All animals survived the 14 day observation period. No macroscopic visible changes were observed at necropsy at the end of the observation period, resulting in a LC50 value of > 4250 mg/m³ (4.25 mg/L) for the inhalation of aerosol.

Classification for acute inhalation toxicity is not necessary according to Regulation (EC) No 1272/2008 .

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
> 4 250 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
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Remarks on result:
other: corresponds to 1710 mg/kg bw pure Pigment Yellow 13; no animals died within the observation period
Mortality:
- no deaths occurred
Clinical signs:
other: - no clinical symptoms were recorded
Gross pathology:
- No macroscopically visible changes occurred at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was not toxic to male and female Sprague-Dawley rats after dermal application, resulting in a dermal LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).
The test was performed with the test item which contains relevant amounts of the submission substance. Therefore, the test results are considered adequate to fulfil the endpoint requirements.
Executive summary:

Acute dermal toxicity of the test item was tested in male and female Sprague-Dawley rats. The maximal applicable dose (3 g test item /kg bw suspended in polyethylene glycol:water 50:50 - final volume 9.9 ml; corresponding to 1710 mg PY13/kg bw) were applied to the skin. No clinical signs were observed and no animals died during the 7 day observation period, resulting in a LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).

Classification for acute dermal toxicity is not necessary according to Regulation (EC) No 1272/2008.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
: no details given on the duration of the exposure; no details given on the occlusion made on the application site; dose tested (1710 mg/kg bw) is lower than the recommended limit dose (2000 mg/kg bw); only 7 days postobservation period
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: in house breeding
- Age at study initiation: 8 weeks
- Weight at study initiation: males mean: 322 g; females mean: 210 g
- Housing: single caged
- Diet: pelleted diet (Oakes of Congleton), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
not specified
Vehicle:
other: 50:50 mixture: polyethylene glycol/water
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg bw
- For solids, paste formed: yes (1 g of test item was mixed with 2.5 ml of vehicle)
Duration of exposure:
no data
Doses:
9.9 ml of paste per kg bw (equivalent to 3000 mg test item per kg bw)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Remarks on result:
other: corresponds to 1710 mg/kg bw pure Pigment Yellow 13; no animals died within the observation period
Mortality:
- no deaths occurred
Clinical signs:
other: - no clinical symptoms were recorded
Gross pathology:
- No macroscopically visible changes occurred at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item was not toxic to male and female Sprague-Dawley rats after dermal application, resulting in a dermal LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).
The test was performed with the test item which contains relevant amounts of the submission substance. Therefore, the test results are considered adequate to fulfil the endpoint requirements.
Executive summary:

Acute dermal toxicity of the test item was tested in male and female Sprague-Dawley rats. The maximal applicable dose (3 g test item /kg bw suspended in polyethylene glycol:water 50:50 - final volume 9.9 ml; corresponding to 1710 mg PY13/kg bw) were applied to the skin. No clinical signs were observed and no animals died during the 7 day observation period, resulting in a LD50 > 3000 mg/kg bw (corresponding to > 1710 mg PY13/kg bw).

Classification for acute dermal toxicity is not necessary according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 710 mg/kg bw
Quality of whole database:
reliable

Additional information

Justification for classification or non-classification

Based on the reported study data Diarylide Yellow Pigment 12 has not to be classified for acute toxicity according to Regulation (EC) No 1272/2008 and Council Directive 67/548/EEC.

Furthermore, Diarylide Yellow Pigment 12 has not 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.