Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33.6 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR110 and ECHA guidance
Overall assessment factor (AF):
52.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 763.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
In a repeated dose toxicity study (OECD 408) with parts of OECD 416 (evaluation of sperm parameters, organ weight and histopathological examination in P and F1), groups of 20 rats (males and females) were exposed daily to 100; 300 and 1000 mg/kg bw per day. The NOAEL for the systemic toxicity was 1000 mg/kg bw per day in this study. No treatment-related change was observed at any dose levels For route-to-route extrapolation, the calculation approach follows the Guidelines predefined (see R:8-2). Step 1) Relevant dose-descriptor: NOEL, rat = 1000 mg/kg bw per day Step 2) Modification of starting point - Conversion into inhalation NOAEC (in mg/m³) by using an 8-hour respiratory volume for the rat: 0.38 m³/kg bw - Correction for activity driven differences of respiratory volumes in workers compared to workers in rest: 6.7 m³/10 m³ - Correction for inhalation to oral absorption: no factor is added. Justification: the test substance has a low volatility (boiling point above 150°C, vapour pressure of less than 0.5 kPa). - No difference in oral and inhalation absorption is expected between rats and human. NOAEC corrected = 1000*1/0.38*6.7/10 = 1763.2 mg/m³
AF for dose response relationship:
1
Justification:
NOAEL determined
AF for differences in duration of exposure:
1
Justification:
Exposure shorter than the duration of the full spermatogenic cycle but histopathology evaluation of the reproductive organs. Reproduction and developmental toxicity is not exposure duration dependant.
AF for interspecies differences (allometric scaling):
1
Justification:
inhalation route-scaling induced in corrected dose descriptor
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
3
Justification:
Key study = OECD 408 with parts of OECD 416. Repeated dose toxicity study: lower sensitivity compared to OECD 416 but evaluation of sperm parameters, organ weight and histopathology in P and F1 (as described in OECD 416 paragraphs 29-32, 39, 41-44)
AF for remaining uncertainties:
1.4
Justification:
lower groupe size compared to OECD 416
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.76 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR110
Overall assessment factor (AF):
210
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
In a repeated dose toxicity study (OECD 408) with parts of OECD 416 (evaluation of sperm parameters, organ weight and histopathological examination in P and F1), groups of 20 rats (males and females) were exposed daily to 100; 300 and 1000 mg/kg bw per day. The NOAEL for the systemic toxicity was 1000 mg/kg bw per day in this study. No significant treatment-related change was observed at any dose levels. Step 1) Relevant dose-descriptor: NOAEL, rat = 1000 mg/kg bw per day Step 2) Modification of starting point: Correcting for dermal to oral absorption: factor of 1 is used. As no dermal penetration study is available, 100% absorption will be considered as a worst case. No difference in oral and dermal absorption is expected between rats and human. Corrected dermal NOAEL: 1000 mg/kg-day x 100%/100% = 1000 mg/kg-day.
AF for dose response relationship:
1
Justification:
NOAEL determined
AF for differences in duration of exposure:
1
Justification:
Exposure shorter than the duration of the full spermatogenic cycle but histopathology evaluation of the reproductive organs. Reproduction and developmental toxicity is not exposure duration dependant.
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
3
Justification:
Key study = OECD 408 with parts of OECD 416. Repeated dose toxicity study: lower sensitivity compared to OECD 416 but evaluation of sperm parameters, organ weight and histopathology in P and F1 (as described in OECD 416 paragraphs 29-32, 39, 41-44)
AF for remaining uncertainties:
1.4
Justification:
Lower group size compared to OECD 416
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

No DNEL is required for oral exposure of workers since no significant exposure occurs by this route for trained workers (who do not smoke, eat or drink when manipulating chemicals).

No DNELs are required for acute toxic effects, sensitization, irritation and mutagenic effects because the substance does not possess these properties and long-term DNELs are sufficient to cover systemic effects, as a worst-case. Furthermore most of these DNELs can not be calculated with the available qualitative or single-dose data.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

No assessment and notably no DNEL is required for the general public, as the latter is only exposed to the substances via the use of final cosmetic products. Assessment of human health effects for such exposure is not required by REACH.