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Description of key information

Results for acute oral toxicity were based on a constituent of the target substance. A study similar to OECD401 is performed with CAS 85186-64 -7: LD50> 10000 mg/kg bw. For the substance itself a 14 -day range finder is available which indicates that this substance might be more toxic compared to CAS 85186-64 -7. Overall, the data on acute oral toxicity is inconclusive.

Acute dermal toxicity: A study according to OECD402: LD50 > 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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached read-across justification.
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Result read-across source CAS No. 85186-64-7. Correction for molecular weight not required
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 mg/kg bw

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:
15 Aug 2016 to 9 Sep 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Version / remarks:
November 24, 2000
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay Labor für biologische Analytik GmbH, 69120 Heidelberg
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name as cited in study report: Orasol Black X51
- Test item No.: 16/0074-1
- Batch identification: 001-150606
- Content: App. 95 % can be assumed.
- Expiry date: May 26, 2020
- Storage conditions: Room temperature
- Physical state/ color: Solid / black
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 week
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight): 225 to 241 (males) or 200 to 217 (females)
- Housing: Single housing in Makrolon cage, type III with Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria as enrichment. As bedding material H 15005-29 was added; Ssniff, spezialdiäten GmbH (Experimeental Diets INc. 59494 Soest, Germany)
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
corn oil
Remarks:
Ph.Eur.
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm²
- % coverage: At least 10% of the body surface
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).
- Clipping of the fur: About 24 hours before application

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Afterwards removal of the semi-occlusive dressing, rinsing of the application site with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 20 g/ 100 mL (suspension)

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/ kg bw
Duration of exposure:
24 hours
Doses:
2000 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
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Clinical observations: Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.
- Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Scoring of skin findings: Individual readings for skin findings 30 to 60 minutes after removal of the semi-occlusive dressing (day 1), and several times thereafter and on the last day of observation.
- Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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 mortality occurred
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
The body weights of the male animals and of two female animals increased within the normal range throughout the study period. Two female animals showed a stagnation of body weight during the first week while in another female a marginal loss of body weight was noted. The body weights of the affected females increased in a normal range during the second week. Due to the fact that stagnation or marginal loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
Local effects: Due to the black discoloration of the application area, no erythema could be determined from study day 1 until study day 2 in all animals. Thereafter, no local effects were observed in all animals.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

For acute oral and inhalation toxicity no substance-specific data are available. Therefore, this information is derived from the consituent with CAS 85186-64 -7. For acute dermal toxicity a study with the test substance itself is available. For the oral route however, the obtained effect level is not in line with the obervations in a 14 -day range finder with the substance itself.

Acute oral toxicity, equivalent to OECD401 (source substance CAS 85186-64 -7)

Gassner rats were exposed by oral gavage to the test substance (5 animals/sex/dose) at dosage levels of 8000 and 10000 mg/kg bw administered as a 30% solution in CMC. Animals were subjected to observations during a period of 7 days in which mortality (observations after 1, 24 and 48 hours and 7 days) and clinical signs were recorded. Necropsy on survivors was performed as well. During the observation period dematiaceous faeces were observed, no further clinical signs or abnormalities on the organs were reported. No mortality occurred. Based on these data, an LD50 of >10000 mg/kg was determined for both males and females (BASF 1972).

14 day dose-range finder with the substance itself

The objective of this dose range finder was to select dose levels for a combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test of in Wistar Han rats by oral gavage. The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test item. The substance was administered as a suspension in propylene glycol at dose levels of 1000, 200, 50 and 100 mg/kg bw/day (group 2, 3, 4 and 5) subsequently to 4 males and 4 females. A vehicle control group (group 1 was taken along). Chemical analyses of formulations for Groups 1, 2 and 3 were conducted once during the study to confirm accuracy and homogeneity. No chemical analyses was performed for the last added two Groups 4 and 5. The following parameters and end points were evaluated in this study: clinical signs, bodyweights, food consumption, clinical pathology (haematology, coagulation and clinical chemistry), gross necropsy findings and organ weights. Administration of the substance was not tolerated at dose levels of 100, 200 and 1000 mg/kg bw/day. Within 3 to 5 days (1000 and 200 mg/kg bw/day) and 9 to 11 days (100 mg/kg bw/day) all animals were either found dead or euthanizedin extremis(in the 200 mg/kg bw/day group only). This high toxicity was not expected based on the available data from an acute toxicity study indicating an LD50 > 10000 mg/kg bw/day. General observations prior to their deaths included piloerection (both sexes) and hunched posture (females only), body weight loss and reduced food consumption (absolute and relative to body weight). Severity increased with higher dose, and females seemed to be more sensitive to treatment than males. At necropsy, two females at 1000 mg/kg bw/day had several to many, purple foci on their thymus. In addition, all animals were noted with bluish discoloration of their bodies, including internal tissues/organs, which most likely was related to the black colour of the test item. In these groups, organ weights of liver, kidneys, adrenals and spleen could only be determined for the animals at 200 mg/kg/day that were euthanizedinextremis. Incidental changes included increased weights of liver and kidneys (one male and one female), increased weight of adrenals (one male). No data on clinical laboratory parameters are available from all these animals that died preterm. Only limited toxicity was seen at 50 mg/kg bw/day. In-life findings included piloerection (both sexes) and hunched posture (females only). At end of treatment (Day 15), blood levels of cholesterol were markedly decreased (both sexes). In addition, higher levels of bile acids were recorded in one male and all females. There were no test item-related mortalities, bodyweight and food consumption remained within the normal range, and no clear changes in haematology parameters (incl. clotting) and organ weights were noted. In conclusion, based on the results of this dose range finder, doses of 5, 15 and 50 mg/kg bw/ day were selected for the combined 28-day repeated dose toxicity study with the reproduction/ developmental toxicity screening test (Charles River Laboratories 2018).

Acute inhalation toxicity (source substance CAS 85186-64 -7)

In an inhalation hazard test in rats, 12 male and female rats were exposed to saturated vapour (generated at 200 °C) of the test substance for 8 hours at a mean concentration of 1.58 mg/L. In a one week exposure period, mortality and clinical signs were recorded. Necropsy was scheduled at the end of the exposure period. Observations were performed at 3, 10 and 30 minutes and 1, 3 and 8 hours. Due to a technical problem, which caused all animals to die, the study was discontinued. No conclusion based on this study could be formed. (BASF 1972).

Acute dermal toxicity, OECD 402

In an acute dermal toxicity study (Limit Test according to OECD 402 and GLP), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw. The test substance was applied as suspension in corn oil Ph.Eur. The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days for mortality, clinical sighs and body weight. Gross pathology was performed at the end of the study. During the observation period, no mortality occurred, no signs of systemic toxicity were observed. Local effects were assigned within the first two days after application since due to the black discoloration of the application area, erythema could not be determined from study day 1 until study day 2. The body weights of the male animals and of two female animals increased within the normal range throughout the study period. Two female animals showed a stagnation of body weight during the first week while in another female animal a marginal loss of body weight was noted. Due to the fact that stagnation or marginal loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific. Based on these data, the LD50 exceeds the limit dose of 2000 mg/kg bw (Bioassay 2016).

Justification for classification or non-classification

Based on the results of the available studies, classification of the substance for acute dermal toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008. The data on acute oral toxicity is inconclusive.