Distillation residue, butyl alcohols production, rectification

Endpoint summary

Description of key information

Acute oral toxicity: LD50 (rat;male/female) > 2000 mg/kg bw / day
Acute inhalation toxicity: No study available
Acute dermal toxicity: LD50 (rat; male/female) > 2000 mg/kg bw / day

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-05-30 TO 2010-07-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD technical guideline 423 - Acute Oral Toxicity study following GLP with no deviations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Accredited Breeding Velaz Prague Czech Republic
- Age at study initiation: no data
- Weight at study initiation: 190-200g females, 240-290g males
- Fasting period before study: overnight
- Housing: Animals were housed in experimental animal house on the bedding (wooden grate) in groups by maximum of 3 in cage in conformity with laboratory animals welfare legistlation.
- Diet (e.g. ad libitum): ad libitum. A standard certified laboratory diet (supplier Top Dovo, Dobra Voda) was served. The diet is routinely analysed by the manufacturer for nutritional components and environmental contaminants.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2
- Humidity (%): 55 +-10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 30 May 2010 To: 21 July 2010

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

Aqua pro inujectione (Imuna), Lot 0621VA - H2O

Details on oral exposure:

VEHICLE
- Concentration in vehicle: undiluted
- Lot/batch no. (if required): Lot 0621VA - H2O

MAXIMUM DOSE VOLUME APPLIED: 0,674 ml

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the low acute toxicity of the main identified constituent 2-ethylhexanol.

Doses:

Fixed dose 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 minutes, periodically during first 24 hours (first 4 hours), daily until 14 days. Body weights measured weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

No toxicity observed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The substance was recognized as orally non-toxic up to 2000 mg/kg bw in a well-established study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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:

2010-05-30 TO 2010-07-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: An acute dermal toxicity study according to OECD technical guideline 402, following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Accredited Breeding Velaz Prague Czech Republic
- Age at study initiation: no data
- Weight at study initiation: 190-210g females, 220-290g males
- Fasting period before study: overnight
- Housing: Animals were housed in experimental animal house on the bedding (wooden grate) in groups by maximum of 3 in cage in conformity with laboratory animals welfare legistlation.
- Diet (e.g. ad libitum): ad libitum. A standard certified laboratory diet (supplier Top Dovo, Dobra Voda) was served. The diet is routinely analysed by the manufacturer for nutritional components and environmental contaminants.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2
- Humidity (%): 55 +-10
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 30 May 2010 To: 22 July 2010

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10% of total body surface
- Type of wrap if used: porous gauze patch covered with nonpermeable folio by means of a semi-occlusive dressing and non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): fully absorbed

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,440 - 0,670 ml
- Concentration (if solution): undiluted
- Constant volume or concentration used: no, adjusted by body weight

VEHICLE
- Amount(s) applied (volume or weight with unit): undiluted

Duration of exposure:

14 days

Doses:

Fixed dose 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: first 30 minutes, periodically the first 24 hours and daily until 14 days. Bodyweights measured at the beginning, after one week and the end of the experiment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities.

Clinical signs:

other: Tested product applied to 5 male and 5 female rats in limit dose 2000 mg/kg did not cause death either visible symptoms of toxicity during first 4 hours after application or 14 day observation period.

Gross pathology:

All 5 males and 5 females had survived observation period and were necropsied after euthanasia. During necropsy no macroscopically changes were noticed.

Other findings:

Test compound was fully absorbed without residuum. Any excessive irritation was not observed in the site of application after removing of semiocclusive bandage.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The substance was recognized as dermally non-toxic up to 2000 mg/kg bw in a well-established study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute toxicity

There is available an acute oral toxicity study for the target substance by Hameln r.d.s (2010). The study was conducted according to the OECD 423 guideline and according to GLP. An acute limit oral testing exhibited no toxicity up to 2000 mg/kg bw.

Testing via inhalation route cannot be considered a risk due to low vapour pressure of the substance and thus would have required most probably generation of aerosols to derive effect levels. Therefore acute inhalation toxicity is not considered relevant for workers or general population, but is taken qualitatively account for elevated temperatures (chapter 9 of CSR).

There is available an acute dermal toxicity study for the target substance by Hameln r.d.s (2010). The study was conducted according to the OECD 402 guideline and according to GLP. An acute limit dermal testing exhibited no toxicity up to 2000 mg/kg bw.

Aspiration toxicity

Based on the dynamic viscosity at 40 deg. C and the density of the substance (851.3 kg/m³), the kinematic viscosity is calculated to be 2.784 mm²/s. As the target substance is a hydrocarbon and the calculated kinematic viscosity is less than 20.5 mm²/s, the substance may cause aspiration hazard.

Justification for selection of acute toxicity – oral endpoint
Reliable, guideline compliant study conducted for the target substance.

Justification for selection of acute toxicity – inhalation endpoint
The target substance does not cause a concern for acute inhalation toxicity due to low vapor pressure at room temperature.

Justification for selection of acute toxicity – dermal endpoint
Reliable, guideline compliant study conducted for the target substance.

Justification for classification or non-classification

Based on the well established acute tests of the target substance, there is no need to classify the substance for acute health hazards according to CLP Regulation 1272/2008 and according to Directive 67/548/EEC.

Based on the kinematic viscosity of the target substance (2.784 mm2/s) measured at 40 °C, the substance is classified for Asp.Tox. 1. according to CLP Regulation 1272/2008 and for Xn; R65 according to Directive 67/548/EEC.