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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Repeated dose toxicity - oral:

A seven day dietary study of low reliability (Klimisch 4) was conducted in rats with doses of 0, 150, 220 and 320 mg/kg bw/day (Carnegie-Mellon, 1975).  No significant effects were associated with the 150 mg/kg/day dose, which was considered the NOEL for systemic toxicity.

Repeated dose toxicity - inhalation:

A 90 day whole body vapour inhalation study was conducted in rats similar to OECD guidelines with a reliability score of 2 (BRRC, 1993). Doses were 0, 0.22, 1.25 and 5.8 ppm (1.51, 8.2 and 38 mg/m3). There were signs of ocular and respiratory irritation at all doses. The NOAEC for systemic effects is considered to be 1.25 ppm (8.2 mg/m3).  An LOAEC value for local effects of 0.23 ppm (1.51 mg/m3) was determined based on various signs of eye and respiratory tract irritation at all concentrations.

Repeated dose toxicity - dermal:

A 90 day dermal study was conducted in rabbits according to OECD guideline 411 with a reliability score of 2 (BRRC, 1984). The NOAEL for systemic effects was considered to be greater than the highest tested dose of 8.0 mg/kg bw/day.  All dose levels tested resulted in varying levels of irritation at the exposure site.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available
Study duration:
subacute
Species:
rat
Quality of whole database:
No studies of sufficient quality or reliability are available for this endpoint.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
8.2 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
A 90 day whole body vapour inhalation study was conducted in rats similar to OECD guidelines with a reliability score of 2. No other reliable repeated dose inhalation studies are available for this substance.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
1.51 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
A 90 day whole body vapour inhalation study was conducted in rats similar to OECD guidelines with a reliability score of 2. No other reliable repeated dose inhalation studies are available for this substance.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
8 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
A 90 day dermal study was conducted in rabbits according to OECD guideline 411 with a reliability score of 2. Due to the test substance being corrosive, local irritation effects prevented appropriately high systemic exposure to occur. For this reason, a NOAEL is not reported here. No other reliable repeated dose dermal studies are available for this substance.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
A 90 day dermal study was conducted in rabbits according to OECD guideline 411 with a reliability score of 2. Varying levels of skin irritation were seen at all dose levels and thus a NOAEL could not be derived for local effects. No other reliable repeated dose dermal studies are available for this substance.

Additional information

Repeated dose toxicity - oral:
No studies of sufficient quality are available for this endpoint.

A seven day dietary study of low reliability (Klimisch 4) was conducted in rats with doses of 0, 150, 220 and 320 mg/kg bw/day (Carnegie-Mellon, 1975).  No significant effects were associated with the 150 mg/kg/day dose, which was considered the NOEL for systemic toxicity. An LOAEL for local effects is established at 220 mg/kg bw/day.


Repeated dose toxicity - inhalation:
A 90 day whole body vapour inhalation study was conducted in rats similar to OECD guidelines with a reliability score of 2. Doses were 0, 0.23, 1.25 and 5.8 ppm (1.51, 8.2 and 38.0 mg/m3). There were signs of ocular and respiratory irritation at all doses. Evidence of minor, non-specific systemic toxicity (weight loss, changes in urinalysis and increase in relative weight of the testes and adrenals in males) was only observed at the highest dose of 5.8 ppm (38 mg/m3). No target organ toxicity was observed at any dose level. The NOAEC for systemic effects is therefore considered to be 1.25 ppm (8.2 mg/m3). An LOAEC value for local effects of 0.23 ppm (1.51 mg/m3) was determined on the basis of various signs of eye and respiratory tract irritation at all concentrations. A NOAEC could not be determined for irritancy under the conditions of this study as signs of irritation were observed in male and female rats even at the lowest concentration.

Two short-term toxicity studies via inhalation of low reliability (K4) were available (BRRC, 1988; BRRC, 1989).


Repeated dose toxicity - dermal:
A 90 day dermal study was conducted in rabbits according to OECD guideline 411 with a reliability score of 2 (BRRC, 1984). Doses were 2.0, 0.7 and 0.2% corresponding to nominal doses of 8.0, 2.8 and 0.27 mg/kg/ bw/day, 6 hours per day, 5 days per week. The doses were chosen based on a range-finding study that showed local irritation at the lowest dose tested (2.5%). There were no effects at any dose on body weight and food consumption, gross pathology, histopathology or organ weights. The NOAEL was considered to be greater than the highest tested dose of 8.0 mg/kg bw/day. All dose levels tested resulted in varying levels of irritation at the exposure site. A DNEL could not be derived as, per Chapter R.8 of the ECHA Guidance, a DNEL should preferably cover both systemic and local effects. DNELs for systemic effects can in principle be based on all types of studies, unless low dose local effects prevent appropriately high systemic exposure to occur.
Daily recurrent application of the test substance to intact skin of rabbits, over a period of 90 days at concentrations of 2.0, 0.7, and 0.2% produced local dermal inflammation (including: erythema, edema, desquamation, fissuring, and by microscopic examination epidermal vacuolization and acanthosis were observed) but no signs of toxicity.
A DNEL could not be derived for local effects (irritation/corrosion). Varying levels of skin irritation were seen at all dose levels and thus a NOAEL could not be derived for local effects. No statistical analysis was provided therefore a LOAEL could not be determined. Following the ECHA Guidance, a qualitative assessment will be performed.

A short-term repeated dose toxicity study via dermal administration of low reliability was available.

Justification for classification or non-classification

Based on the outcomes of the available repeated dose studies, classification for specific target organ toxicity - after repeated exposure is not required according to Regulation (EC) 1272/2008 (CLP).