Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.92 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
655 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
10
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
655 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
10

Workers - Hazard for the eyes

Additional information - workers

Inhalation exposure:

Inhalation is not a relevant exposure route for this substance due to its physicochemical properties (very low vapour pressure (<0.000001 hPa at 20 and 50°C) and high melting point (133.5°C)). Therefore, the potential for the generation of inhalable forms is low. Furthermore, the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Therefore, no inhalation DNELs have been established.

 

Acute/short-term exposure - systemic effects:

According to ECHA Guidance on information requirements and CSR, chapter R8, a DNEL for acute systemic toxicity should be derived only if an acute systemic toxicity hazard leading to C&L has been identified.

The substanceis classified for acute oral toxicity (Xn, R22).However, the oral route is no relevant exposure route for workers. The substance was practically non-toxic in a dermal acute toxicity study in rats (LD50 > 2000 mg/kg; BASF SE, 2010). There is no acute inhalation toxicity study available. However, inhalation is not a relevant exposure route for this substance. Therefore, the substance is not subject to classification and labelling for acute dermal or inhalation toxicity. Consequently, the establishment of DNELs for acute/short-term exposure - systemic effects is not required.

 

Acute/short-term and long-term exposure - local effects:

The substance is irritating to the skin and poses the risk of serious damage to eyes (C&L R38/Skin irrit. Cat 2 and R41/Eye irrit. Cat. 1 according to Directive 67/548/EEC and Regulation 1272/2008/EC (EU GHS), respectively). The available in vitro skin and eye irritation studies allow only a qualitative assessment of irritation/corrosion following acute exposure. Therefore, no DNELs have been established for these effects.

 

Experimental data on respiratory irritation are not available, but inhalation is not an anticipated exposure route for this substance, and therefore no DNEL was established.

 

In a murine local lymph node assay (LLNA) the substance was sensitising to the skin (BASF SE, 2010). Accordingly, the substance is classified and labelled with R43 according to Directive 67/548/EEC and Skin sens. Cat 1B / H317 according to Regulation 1272/2008/EC. An induction-specific DNEL was derived for skin sensitisation based on the EC3 value from the above-mentioned LLNA. The sensitisation threshold (EC3 value) was reported to be 26.2% w/v, indicative of a sensitiser of moderate potency. According to the Guidance on information requirements and chemical safety assessment, Chapter R.8, the EC3 value (in µg/cm²) can be used as a surrogate for the NOAEL for induction. EC3 data generally correlate well with human skin sensitisation thresholds. However, there are cases where this correlation is poor and the two values may differ by 10-fold or more. Therefore, using the formula EC3[%]*250 [µg/cm²/%] = EC3 [µg/cm²] and the default assessment factor of 10 for interspecies variation, a DNEL for local effects after dermal exposure was established at 655 µg/cm².

 

Long-term exposure - systemic effects:

In a combined repeated dose toxicity study with reproduction/developmental screening test according to OECD guideline 422 the substance was administered by gavage to 12 rats per sex and dose of 0, 175, 350 and 700 mg/kg. It was shown, that in males and females of the groups of 350 mg/kg or 700 mg/kg respectively, mucosal hyperplasia in the stomach limiting ridge and mucosal atrophy in the cardiac region were seen. Furthermore, in males and females of the 700 mg/kg group, erosion and superficial hemorrhage in the glandular stomach and soft feces with partial black changes were observed. Moreover, males of the 700 mg/kg group exhibited retarded body weight gain, low food consumption, low values for mean corpuscular volume and mean corpuscular hemoglobin, low values for total protein and α1-globulin fraction ratio. In females, of the 700 mg/kg group, 1 animal died and 1 animal was sacrificed in extremis, and also retarded body weight gain was observed. Based on the findings in this study the NOAEL was determined to be 175 mg/kg/day. This NOAEL was used as the point of departure for the establishment of a dermal DNEL for systemic effects.

 

- Dermal exposure:

Taking into account a 2-fold lower dermal absorption in comparison to oral absorption (assumption based on lack of systemic toxicity in acute dermal toxicity study and DERMWIN v2.09 calculation) the calculated NOAEL following dermal application is 350 mg/kg bw /day (175 mg/kg bw /day * 2).

 

The following assessment factors were used for the derivation of the long-term DNEL for dermal exposure:

- Inter-species factor: 4 (allometric scaling); the additional factor of 2.5 is not applied because there is no evidence for species differences in the general mode of action or kinetics

- Intra-species factor (worker): 5 (default)

- Exposure duration factor (subacute to chronic): 6 (default)

- Dose-response: 1 (default)

- Quality of whole database: 1 (default)

 

The DNEL was calculated as follows:

DNEL (worker, long-term dermal exposure, systemic effects): 350 mg/kg bw/day / (4*5*6) = 2.92 mg/kg bw/day.

 

- Inhalation exposure:

Inhalation is not a relevant exposure route for this substance. Therefore, inhalation DNELs have not been derived.

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

The substance is neither marketed to the general public nor intentionally added to consumer products. Also, consumer products do not contain compounds from which the substance is intended to be released. Thus, the derivation of DNELs for the general population is not required.