Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Macrolex Rotviolett R = C. I. Disperse Violet

(CAS No. 6408-72-6)

DNELs (worker/general population)

I. Introduction:

Classification

Harmonized classification – Annex VI of Regulation (EC)  (No 1272/2008 (CLP Regulation):

Not classified

Self-classification: Not classified

Known occupational exposure limit(s):

SCOEL: no data

TRGS 900: no data

MAK: no data

Remarks/Limitations

No remarks/limitations

DNELs (worker)

II: Conclusion - worker (systemic and local effects):

 Route of exposure

     Local effect

 Systemic effect

 Dermal (long term)  

No hazard identified

 No hazard identified

 Dermal (short term)

No hazard identified

No hazard identified

Inhalation (long term)

No hazard identified

 No hazard identified

 Inhalation (long term)  No hazard identified  No hazard identified
 Hazard for eyes     No hazard identified

III. DNEL systemic (worker)

In an OECD Guidelines 407 (Repeated Dose 28 Day Oral Toxicity Study in Rodents) three groups, each of five male and five female Wistar rats, received Macrolex Rotviolett R at dose levels of 100, 300 or 1000 mg/kg bw/day by gavage, for twenty-eight consecutive days. A control group of five males and five females was dosed with vehicle alone (Arachis oil BP).

Clinical signs, functional observations, body weight change, dietary intake and water consumption were monitored during the study.  Hematology and blood chemistry were evaluated for all animals at the end of the study.

All animals were subjected to gross necropsy examination and histopathological evaluation of selected tissues from the 1000 mg/kg bw/day and control animals was performed.

The oral administration 100, 300 or 1000 mg/kg bw/day was well tolerated and did not result in any toxicologically significant effects. The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was 1000 mg/kg bw/day (high dose) within the confines of this study type.

Long-term toxicity (oral, dermal, inhalation) – systemic effects (worker)

In the key study for oral toxicity a NOAEL = 1000 mg/kg bw/day was found (highest applied dose). No repeated dose studies for inhalation or dermal toxicity are available.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

Worker DNEL long-term for oral, dermal, inhalation exposure: no hazard identified

Short-term toxicity (oral, dermal, inhalation) – systemic effects (worker)

In the key study for oral toxicity a LD50 > 5000 mg/kg bw was found. No studies for acute inhalation or acute dermal toxicity are available.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

Worker DNEL short-term for oral, dermal, inhalation exposure: no hazard identified

Reproductive Toxicity – systemic effects (worker)

In an OECD guideline 421 (Reproduction/Developmental Toxicity Screening Test) Macrolex Rotviolett R was administered by gavage to three treatment groups for approximately six weeks for males and throughout a two week pre-pairing phase, pairing, gestation and lactation to Day 13 for females, at dose levels of 100, 300 and 1000 mg/kg bw/day.  Each treatment groups initially consisted of twelve male and twelve female Wistar rats, however an additional female was allocated to the 1000 mg/kg bw/day dosage group due to a non-treatment related death early in the study.  A control group of twelve males and twelve females was dosed with vehicle alone (Arachis oil BP) over the same treatment period.  

The study was performed to screen for potential adverse effects of the test item on reproduction, including offspring development, to evaluate some endocrine disruptor relevant endpoints, and provides an initial hazard assessment for effect on reproduction.  

The No Observed Adverse Effect Level for the adult animals was considered to be 1000 mg/kg bw/day (the highest dosage tested).  The No Observed Adverse Effect Level for reproduction and for the growth, development and survival of the offspring was also considered to be 1000 mg/kg bw/day.

In conclusion, no separate DNEL for toxicity to reproduction is required Macrolex Rotviolett R, as the NOAEL for toxicity to reproduction is identical with the NOAEL for repeated-dose toxicity.

Conclusion on systemic DNEL:

For systemic effects:

no hazard identified

VII. DNEL local (worker)

Basis for delineation of the DNELs local (long and short term toxicity):

Irritation/corrosion

Skin irritation:

Several in vivo skin irritation/corrosion studies according or similar to OECD guideline 404 are available. The test items were not irritating to the skin.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Eye irritation:

Several in vivo eye irritation studies according or similar to OECD guideline 405 are available. The test items were not irritating to the eyes.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Sensitization

In an OECD 429 guideline study (Skin Sensitisation: Local Lymph Node Assay) no adverse effect was observed. The test item was not sensitizing (negative).

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Conclusion on local DNEL:

For local effects:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

DNELs (general population)

V: Conclusion - general population (systemic and local effects):

 Route of exposure

  Local effect

 Systemic effect

 Oral (long term)  

 No hazard identified

 No hazard identified

 Oral (short term)   

 No hazard identified

 No hazard identified

 Dermal (long term)

 No hazard identified

 No hazard identified

 Dermal (short term)

 No hazard identified

 No hazard identified

 Inhalation (long term)

 No hazard identified

No hazard identified

Inhalation (short term)

No hazard identified

No hazard identified

 Hazard for eyes

No hazard identified

VI. DNEL systemic (general population)

In an OECD Guidelines 407 (Repeated Dose 28 Day Oral Toxicity Study in Rodents) three groups, each of five male and five female Wistar rats, received Macrolex Rotviolett R at dose levels of 100, 300 or 1000 mg/kg bw/day by gavage, for twenty-eight consecutive days. A control group of five males and five females was dosed with vehicle alone (Arachis oil BP).

Clinical signs, functional observations, body weight change, dietary intake and water consumption were monitored during the study.  Hematology and blood chemistry were evaluated for all animals at the end of the study.

All animals were subjected to gross necropsy examination and histopathological evaluation of selected tissues from the 1000 mg/kg bw/day and control animals was performed.

The oral administration 100, 300 or 1000 mg/kg bw/day was well tolerated and did not result in any toxicologically significant effects. The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was 1000 mg/kg bw/day (high dose) within the confines of this study type.

Long-term toxicity (oral, dermal, inhalation) – systemic effects (general population)

In the key study for oral toxicity a NOAEL = 1000 mg/kg bw/day was found (highest applied dose). No repeated dose studies for inhalation or dermal toxicity are available.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

General population DNEL long-term for oral, dermal, inhalation exposure: no hazard identified

Short-term toxicity (oral, dermal, inhalation) – systemic effects (general population)

In the key study for oral toxicity a LD50 > 5000 mg/kg bw was found. No studies for acute inhalation or acute dermal toxicity are available.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

General population DNEL short-term for oral, dermal, inhalation exposure: no hazard identified

Reproductive Toxicity – systemic effects (general population)

In an OECD guideline 421 (Reproduction/Developmental Toxicity Screening Test) Macrolex Rotviolett R was administered by gavage to three treatment groups for approximately six weeks for males and throughout a two week pre-pairing phase, pairing, gestation and lactation to Day 13 for females, at dose levels of 100, 300 and 1000 mg/kg bw/day.  Each treatment groups initially consisted of twelve male and twelve female Wistar rats, however an additional female was allocated to the 1000 mg/kg bw/day dosage group due to a non-treatment related death early in the study.  A control group of twelve males and twelve females was dosed with vehicle alone (Arachis oil BP) over the same treatment period.  

The study was performed to screen for potential adverse effects of the test item on reproduction, including offspring development, to evaluate some endocrine disruptor relevant endpoints, and provides an initial hazard assessment for effect on reproduction.  

The No Observed Adverse Effect Level for the adult animals was considered to be 1000 mg/kg bw/day (the highest dosage tested).  The No Observed Adverse Effect Level for reproduction and for the growth, development and survival of the offspring was also considered to be 1000 mg/kg bw/day.

In conclusion, no separate DNEL for toxicity to reproduction is required Macrolex Rotviolett R, as the NOAEL for toxicity to reproduction is identical with the NOAEL for repeated-dose toxicity.

Conclusion on systemic DNEL:

For systemic effects:

no hazard identified

VII. DNEL local (general population)

Basis for delineation of the DNELs local (long and short term toxicity):

Irritation/corrosion

Skin irritation:

Several in vivo skin irritation/corrosion studies according or similar to OECD guideline 404 are available. The test items were not irritating to the skin.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Eye irritation:

Several in vivo eye irritation studies according or similar to OECD guideline 405 are available. The test items were not irritating to the eyes.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Sensitization

In an OECD 429 guideline study (Skin Sensitisation: Local Lymph Node Assay) no adverse effect was observed. The test item was not sensitizing (negative).

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Conclusion on local DNEL:

For local effects:

no hazard identified